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| Name | Class |
|---|---|
| Medivation, Inc. | INDUSTRY |
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Dimebon will not exhibit abuse potential when compared to placebo or a positive control (alprazolam).
The main purpose for this study is to determine whether dimebon exhibits abuse potential.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| dimebon 20 mg | Experimental |
| |
| dimebon 40 mg | Experimental |
| |
| dimebon 60 mg | Experimental |
| |
| placebo | Placebo Comparator |
| |
| alprazolam 1 mg | Active Comparator |
| |
| alprazolam 3 mg | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| dimebon | Drug | Oral tablet; 20 mg dimebon, single dose |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Drug liking VAS is one of the measures of balance of effects that assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar visual analogue scale (VAS) anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the left with "strong disliking" (score of 0 mm) and on the right with "strong liking" (score of 100 mm). Emax is largest effect score between 0.5 to 24 hours post-dose. Emin is smallest effect score between 0.5 to 24 hours post-dose. | 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose |
| Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Overall drug liking VAS is one of the measures of balance of effects that assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carryover effects). A 100 mm bipolar VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = "strong disliking", 50 mm= "neither like nor dislike", and 100 mm= "strong liking"). Emax is the largest effect score between 6 to 24 hours post-dose. Emin is the smallest effect score between 6 to 24 hours post-dose. | 6, 12, 24 hours post-dose |
| Balance of Effects- Take Drug Again VAS: Peak Effect (Maximum Effect [Emax]) | Take drug again VAS is one of the measures of balance of effects. It is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm bipolar VAS with score ranging from 0 mm to 100 mm (score of 0 mm = "definitely not", 50 mm = "do not care", and 100 mm = "definitely so"). Emax is largest effect score between 6 hours to 24 hours. | 6, 12, 24 hours post-dose |
| Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
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| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | PBO, ALP 1mg, DIM 60 mg, ALP 3 mg, DIM 40 mg, DIM 20 mg | Placebo (PBO) matched to 3 alprazolam (ALP) capsules and placebo matched to 3 dimebon (DIM) tablets on Day 1 in the first intervention period; followed by alprazolam 1 milligram (mg) capsule, placebo matched to 2 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the second intervention period; then dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 in the third intervention period; then alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 in fourth intervention period; then dimebon 40 mg tablets and placebo matched to dimebon tablet and placebo matched to 3 alprazolam capsules on Day 1 in the fifth intervention period; and dimebon 20 mg tablet, placebo matched to 2 dimebon tablets and placebo matched to 3 alprazolam capsules on Day 1 in the sixth intervention period. A washout period of at least 7 days was maintained between each dose. |
| FG001 | ALP 1 mg, ALP 3 mg, PBO, DIM 20 mg, DIM 60 mg, DIM 40 mg | Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the first intervention period; followed by alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 in the second intervention period; then placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the third intervention period; then dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 in the fourth intervention period; then dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 in the fifth intervention period; and dimebon 40 mg tablets, placebo matched to dimebon tablet and placebo matched to 3 alprazolam capsules on Day 1 in the sixth intervention period. A washout period of at least 7 days was maintained between each dose. |
| FG002 | ALP 3 mg, DIM 20 mg, ALP 1 mg, DIM 40 mg, PBO, DIM 60 mg | Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 in the first intervention period; followed by dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 in the second intervention period; then alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the third intervention period; then dimebon 40 mg tablets, placebo matched to dimebon tablet and placebo matched to 3 alprazolam capsules on Day 1 in the fourth interventional period; then placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the fifth intervention period; and dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 in the sixth intervention period. A washout period of 7 days was maintained between each dose. |
| FG003 | DIM 20 mg, DIM 40 mg, ALP 3 mg, DIM 60 mg, ALP 1 mg, PBO | Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets and placebo matched to 3 alprazolam capsules on Day 1 in the first intervention period; followed by dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 in the second intervention period; then alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 in the third intervention period; then dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 in the fourth intervention period; then alprazolam 1mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 in the fifth intervention period; and placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the sixth intervention period. A washout period of at least 7 days was maintained between each dose. |
| FG004 | DIM 40 mg, DIM 60 mg, DIM 20 mg, PBO, ALP 3 mg, ALP 1 mg | Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 in the first intervention period; followed by dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 in the second intervention period; then dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 in the third intervention period; then placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the fourth intervention period; then alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 in the fifth intervention period; and alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 in the sixth intervention period. A washout period of at least 7 days was maintained between each dose. |
| FG005 | DIM 60 mg, PBO, DIM 40 mg, ALP 1mg, DIM 20 mg, ALP 3 mg | Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 in the first intervention period; followed by placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 in the second intervention period; then dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 in the third intervention period; then alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 in the fourth intervention group; then dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 in the fifth intervention period; and alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 in the sixth intervention period. A washout period of at least 7 days was maintained between each dose. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention Period |
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| Washout Period (at Least 7 Days) |
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| Second Intervention Period |
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| Washout Period (at Least 7 Days) |
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| Third Intervention Period |
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| Washout Period (at Least 7 Days) |
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| Fourth Intervention Period |
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| Washout Period (at Least 7 Days) |
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| Fifth Intervention Period |
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| Washout Period (at Least 7 Days) |
| |||||||||||||
| Sixth Intervention Period |
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| ID | Title | Description |
|---|---|---|
| BG000 | Entire Study Population | Includes participants randomized to receive placebo first, alprazolam 1 mg first, alprazolam 3 mg first, dimebon 20 mg first, dimebon 40 mg first and dimebon 60 mg first. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Drug liking VAS is one of the measures of balance of effects that assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar visual analogue scale (VAS) anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the left with "strong disliking" (score of 0 mm) and on the right with "strong liking" (score of 100 mm). Emax is largest effect score between 0.5 to 24 hours post-dose. Emin is smallest effect score between 0.5 to 24 hours post-dose. | The pharmacodynamic analysis population included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period. | Posted | Mean | Standard Deviation | mm | 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose |
|
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The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dry eye | Eye disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D006816 | Huntington Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C010119 | latrepirdine |
| D000525 | Alprazolam |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| dimebon |
| Drug |
Oral tablet; 40 mg dimebon, single dose |
|
| dimebon | Drug | Oral tablet; 60 mg dimebon, single dose |
|
| placebo | Drug | Oral tablet or capsule; placebo, single dose |
|
| alprazolam | Drug | Oral capsule; 1 mg alprazolam, single dose |
|
| alprazolam | Drug | Oral capsule; 3 mg alprazolam, single dose |
|
Good and Bad effects VAS is one of the measures of balance of effects that assesses the effect experienced by the participant on a 100 mm bipolar VAS, anchored in the center with a neutral anchor of neither good nor bad effects (score of 50 mm), on the left with bad effects(score of 0 mm) and on the right with good effects (score of 100 mm). Emax is largest effect score between 0.5 to 24 hours post-dose. Emin is smallest effect score between 0.5 to 24 hours post-dose. |
| 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose |
| Balance of Effects- Subjective Drug Value (SDV): Maximum Effect (Emax) | SDV is one of measures of balance of effects. It is a proxy measure of reinforcing efficacy that involves a series of independent, theoretical forced choices between drug administered and different monetary values. Participants were asked to choose between receiving another dose of same drug or an envelope containing specified amount of money, but they did not receive drug or money as described. Possible score range from 0.25 to 50. Higher score range indicates higher SDV. Emax: largest effect score between 6-24 hours post-dose. | 6, 12, 24 hrs post-dose |
| Positive Effects- Addiction Research Center Inventory (ARCI) Morphine Benzedrine Group (MBG): Maximum Effect (Emax) | ARCI (MBG) is one of the measures of positive effects. It is a set of 16 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with the scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when the answer is opposite to the scoring direction. Score range: 0 to 16, higher score indicated positive effects. Emax: largest effect score between 0 to 24 hours post-dose. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 12, 24 hours post-dose |
| Positive Effects- Good Drug Effects: Peak Effect (Maximum Effect [Emax]) | Good drug effects VAS is one of the measures of positive effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so). Emax is the largest effect score between 0.5 to 24 hours post-dose. | 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose |
| Positive Effects- High VAS: Peak Effect (Maximum Effect [Emax]) | High VAS is one of the measures of positive effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so). Emax is largest effect score between 0 to 24 hours. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose |
| Negative Effects- Bad Drug Effects: Peak Effect (Maximum Effect [Emax]) | Bad effects VAS is one of the measures of negative effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so). Emax is largest effect score between 0.5 to 24 hrs. | 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose |
| Negative Effects- Addiction Research Center Inventory (ARCI) Lysergic Acid Diethylamide (LSD): Maximum Effect (Emax) | ARCI (LSD) is one of the measures of negative effects. It is a set of 14 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when the answer is opposite to scoring direction. Score range: 0 to 14, higher score indicated higher negative effects. Emax: largest effect score between 0 to 24 hours post-dose. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose |
| Sedative Effects- Addiction Research Center Inventory (ARCI) Pentobarbital Chlorpromazine Group (PCAG): Maximum Effect (Emax) | ARCI (PCAG) is one of the measures of sedative effects. It is a set of 15 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with the scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when answer is opposite to scoring direction. Score range: 0 to 15, higher score indicated higher sedative effects. Emax: largest effect score between 0 to 24 hours post-dose. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose |
| Sedative Effects- Alertness/Drowsiness: Minimum Effect (Emin) | Alertness/Drowsiness VAS is one of the measures of sedative effects. It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of "neither drowsy nor alert" (score of 50 mm), on the left with "very drowsy" (score of 0 mm) and on the right with "very alert" (score of 100 mm). Emin is the smallest effect score between 0 to 24 hours post-dose. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose |
| Other Subjective Effects- Any Drug Effects: Peak Effect (Maximum Effect [Emax]) | Any drug effects VAS is one of the measures of other subjective effects. It assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so). Emax is the largest effect score between 0.5 to 24 hours post-dose. | 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose |
| Other Subjective Effects- Drug Similarity | Drug similarity VAS is one of the measures of other subjective effects. It assesses the similarity of the drug recently received by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= not at all similar) to 'extremely' (score of 100 mm= very similar). Recently received drugs were compared with placebo, benzodiazepines, codeine/morphine, Tetrahydrocannabinol (THC), pseudoephedrine. | 12 hours post-dose |
| Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin) | ARCI (BG) is measure of other subjective effects. It is a set of 13 questions in which each question contributes to total score. Participants select 'False' / 'True' for response. One point given for each response that agrees with scoring direction, true items receive score of 1 if answer 'True', false items receive score of 1 if answer 'False'. No points if answer is opposite to scoring direction. Score range: 0 to 13, higher score indicated higher other subjective effects. Emax: largest effect score between 0 - 24 hours post-dose. Emin: smallest effect score between 0 - 24 hours post-dose. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose |
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| Years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Body Mass Index | Mean | Standard Deviation | kilogram/square meter (kg/m^2) |
|
| Placebo |
Placebo matched to 3 alprazolam capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods. |
| OG001 | Alprazolam 1 mg | Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods. |
| OG002 | Alprazolam 3 mg | Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods. |
| OG003 | Dimebon 20 mg | Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods. |
| OG004 | Dimebon 40 mg | Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods. |
| OG005 | Dimebon 60 mg | Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods. |
|
|
|
| Primary | Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Overall drug liking VAS is one of the measures of balance of effects that assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carryover effects). A 100 mm bipolar VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = "strong disliking", 50 mm= "neither like nor dislike", and 100 mm= "strong liking"). Emax is the largest effect score between 6 to 24 hours post-dose. Emin is the smallest effect score between 6 to 24 hours post-dose. | The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period. | Posted | Mean | Standard Deviation | mm | 6, 12, 24 hours post-dose |
|
|
|
|
| Primary | Balance of Effects- Take Drug Again VAS: Peak Effect (Maximum Effect [Emax]) | Take drug again VAS is one of the measures of balance of effects. It is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm bipolar VAS with score ranging from 0 mm to 100 mm (score of 0 mm = "definitely not", 50 mm = "do not care", and 100 mm = "definitely so"). Emax is largest effect score between 6 hours to 24 hours. | The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period. | Posted | Mean | Standard Deviation | mm | 6, 12, 24 hours post-dose |
|
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|
|
| Primary | Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Good and Bad effects VAS is one of the measures of balance of effects that assesses the effect experienced by the participant on a 100 mm bipolar VAS, anchored in the center with a neutral anchor of neither good nor bad effects (score of 50 mm), on the left with bad effects(score of 0 mm) and on the right with good effects (score of 100 mm). Emax is largest effect score between 0.5 to 24 hours post-dose. Emin is smallest effect score between 0.5 to 24 hours post-dose. | The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period. | Posted | Mean | Standard Deviation | mm | 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose |
|
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|
| Primary | Balance of Effects- Subjective Drug Value (SDV): Maximum Effect (Emax) | SDV is one of measures of balance of effects. It is a proxy measure of reinforcing efficacy that involves a series of independent, theoretical forced choices between drug administered and different monetary values. Participants were asked to choose between receiving another dose of same drug or an envelope containing specified amount of money, but they did not receive drug or money as described. Possible score range from 0.25 to 50. Higher score range indicates higher SDV. Emax: largest effect score between 6-24 hours post-dose. | The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period. | Posted | Mean | Standard Deviation | Dollar | 6, 12, 24 hrs post-dose |
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| Primary | Positive Effects- Addiction Research Center Inventory (ARCI) Morphine Benzedrine Group (MBG): Maximum Effect (Emax) | ARCI (MBG) is one of the measures of positive effects. It is a set of 16 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with the scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when the answer is opposite to the scoring direction. Score range: 0 to 16, higher score indicated positive effects. Emax: largest effect score between 0 to 24 hours post-dose. | The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period. | Posted | Mean | Standard Deviation | Units on scale | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 12, 24 hours post-dose |
|
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|
| Primary | Positive Effects- Good Drug Effects: Peak Effect (Maximum Effect [Emax]) | Good drug effects VAS is one of the measures of positive effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so). Emax is the largest effect score between 0.5 to 24 hours post-dose. | The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period. | Posted | Mean | Standard Deviation | mm | 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose |
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| Primary | Positive Effects- High VAS: Peak Effect (Maximum Effect [Emax]) | High VAS is one of the measures of positive effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so). Emax is largest effect score between 0 to 24 hours. | The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period. | Posted | Mean | Standard Deviation | mm | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose |
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| Primary | Negative Effects- Bad Drug Effects: Peak Effect (Maximum Effect [Emax]) | Bad effects VAS is one of the measures of negative effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so). Emax is largest effect score between 0.5 to 24 hrs. | The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period. | Posted | Mean | Standard Deviation | mm | 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose |
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| Primary | Negative Effects- Addiction Research Center Inventory (ARCI) Lysergic Acid Diethylamide (LSD): Maximum Effect (Emax) | ARCI (LSD) is one of the measures of negative effects. It is a set of 14 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when the answer is opposite to scoring direction. Score range: 0 to 14, higher score indicated higher negative effects. Emax: largest effect score between 0 to 24 hours post-dose. | The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period. | Posted | Mean | Standard Deviation | Units on Scale | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose |
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| Primary | Sedative Effects- Addiction Research Center Inventory (ARCI) Pentobarbital Chlorpromazine Group (PCAG): Maximum Effect (Emax) | ARCI (PCAG) is one of the measures of sedative effects. It is a set of 15 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with the scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when answer is opposite to scoring direction. Score range: 0 to 15, higher score indicated higher sedative effects. Emax: largest effect score between 0 to 24 hours post-dose. | The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period. | Posted | Mean | Standard Deviation | Units on Scale | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose |
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| Primary | Sedative Effects- Alertness/Drowsiness: Minimum Effect (Emin) | Alertness/Drowsiness VAS is one of the measures of sedative effects. It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of "neither drowsy nor alert" (score of 50 mm), on the left with "very drowsy" (score of 0 mm) and on the right with "very alert" (score of 100 mm). Emin is the smallest effect score between 0 to 24 hours post-dose. | The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period. | Posted | Mean | Standard Deviation | mm | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose |
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| Primary | Other Subjective Effects- Any Drug Effects: Peak Effect (Maximum Effect [Emax]) | Any drug effects VAS is one of the measures of other subjective effects. It assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so). Emax is the largest effect score between 0.5 to 24 hours post-dose. | The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period. | Posted | Mean | Standard Deviation | mm | 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose |
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| Primary | Other Subjective Effects- Drug Similarity | Drug similarity VAS is one of the measures of other subjective effects. It assesses the similarity of the drug recently received by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= not at all similar) to 'extremely' (score of 100 mm= very similar). Recently received drugs were compared with placebo, benzodiazepines, codeine/morphine, Tetrahydrocannabinol (THC), pseudoephedrine. | The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period. 'n' is signifying those participants who were evaluated for this measure for various drugs for similarity in each treatment group. | Posted | Mean | Standard Deviation | mm | 12 hours post-dose |
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| Primary | Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin) | ARCI (BG) is measure of other subjective effects. It is a set of 13 questions in which each question contributes to total score. Participants select 'False' / 'True' for response. One point given for each response that agrees with scoring direction, true items receive score of 1 if answer 'True', false items receive score of 1 if answer 'False'. No points if answer is opposite to scoring direction. Score range: 0 to 13, higher score indicated higher other subjective effects. Emax: largest effect score between 0 - 24 hours post-dose. Emin: smallest effect score between 0 - 24 hours post-dose. | The pharmacodynamic analysis included all randomized participants in the treatment phase who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter in at least 1 treatment period. | Posted | Mean | Standard Deviation | Units on Scale | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose |
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|
| 0 |
| 32 |
| 11 |
| 32 |
| EG001 | Alprazolam 1 mg | Alprazolam 1 mg capsule, placebo matched to 2 alprazolam capsules, and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods. | 0 | 33 | 30 | 33 |
| EG002 | Alprazolam 3 mg | Alprazolam 3 mg capsules and placebo matched to 3 dimebon tablets on Day 1 of any of the six intervention periods. | 0 | 34 | 34 | 34 |
| EG003 | Dimebon 20 mg | Dimebon 20 mg tablet, placebo matched to 2 dimebon tablets, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods. | 0 | 33 | 18 | 33 |
| EG004 | Dimebon 40 mg | Dimebon 40 mg tablets, placebo matched to dimebon tablet, and placebo matched to 3 alprazolam capsules on Day 1 of any of the six intervention periods. | 0 | 32 | 20 | 32 |
| EG005 | Dimebon 60 mg | Dimebon 60 mg tablets and placebo matched to 3 alprazolam capsules on Day 1 of any of the six interventional periods. | 0 | 31 | 17 | 31 |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 13.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 13.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 13.0 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 13.0 | Non-systematic Assessment |
|
| Chills | General disorders | MedDRA 13.0 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA 13.0 | Non-systematic Assessment |
|
| Feeling of relaxation | General disorders | MedDRA 13.0 | Non-systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA 13.0 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 13.0 | Non-systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 13.0 | Non-systematic Assessment |
|
| Hordeolum | Infections and infestations | MedDRA 13.0 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 13.0 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 13.0 | Non-systematic Assessment |
|
| Excoriation | Injury, poisoning and procedural complications | MedDRA 13.0 | Non-systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 13.0 | Non-systematic Assessment |
|
| Mouth injury | Injury, poisoning and procedural complications | MedDRA 13.0 | Non-systematic Assessment |
|
| Soft tissue injury | Injury, poisoning and procedural complications | MedDRA 13.0 | Non-systematic Assessment |
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| Blood creatinine phosphokinase increased | Investigations | MedDRA 13.0 | Non-systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Disturbance in attention | Nervous system disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Dysarthria | Nervous system disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Head discomfort | Nervous system disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Hypoaesthesia | Nervous system disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Speech disorder | Nervous system disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Euphoric mood | Psychiatric disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Hypervigilance | Psychiatric disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Tension | Psychiatric disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Non-systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 13.0 | Non-systematic Assessment |
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Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D001480 | Basal Ganglia Diseases |
| D002819 | Chorea |
| D020820 | Dyskinesias |
| D009069 | Movement Disorders |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D003072 | Cognition Disorders |
| D006571 | Heterocyclic Compounds |
| Emin |
|
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 19.8432 | 2-Sided | 95 | 13.7627 | 25.9238 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.6029 | Mean Difference (Final Values) | -1.6121 | 2-Sided | 95 | -7.7209 | 4.4967 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.3477 | Mean Difference (Final Values) | -2.9241 | 2-Sided | 95 | -9.0571 | 3.2089 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.9769 | Mean Difference (Final Values) | 0.0908 | 2-Sided | 95 | -6.0850 | 6.2667 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -18.2509 | 2-Sided | 95 | -24.3155 | -12.1864 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -19.5629 | 2-Sided | 95 | -25.6616 | -13.4642 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -16.5480 | 2-Sided | 95 | -22.7036 | -10.3923 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -21.4554 | 2-Sided | 95 | -27.4199 | -15.4908 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | <0.0001 | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | Mean Difference (Final Values) | -22.7673 | 2-Sided | 95 | -28.7925 | -16.7422 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -19.7524 | 2-Sided | 95 | -25.8485 | -13.6563 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0006 | Mean Difference (Final Values) | 12.0888 | 2-Sided | 95 | 5.3225 | 18.8551 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0038 | Mean Difference (Final Values) | 10.0768 | 2-Sided | 95 | 3.3132 | 16.8403 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.2257 | Mean Difference (Final Values) | -4.1875 | 2-Sided | 95 | -10.9890 | 2.6139 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.8042 | Mean Difference (Final Values) | -0.8589 | 2-Sided | 95 | -7.6927 | 5.9750 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.6399 | Mean Difference (Final Values) | -1.6335 | 2-Sided | 95 | -8.5177 | 5.2506 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -16.2763 | 2-Sided | 95 | -23.0228 | -9.5229 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0002 | Mean Difference (Final Values) | -12.9477 | 2-Sided | 95 | -19.7374 | -6.1580 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0001 | Mean Difference (Final Values) | -13.7223 | 2-Sided | 95 | -20.5720 | -6.8727 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -14.2643 | 2-Sided | 95 | -20.9226 | -7.6060 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0016 | Mean Difference (Final Values) | -10.9356 | 2-Sided | 95 | -17.6548 | -4.2165 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0008 | Mean Difference (Final Values) | -11.7103 | 2-Sided | 95 | -18.5055 | -4.9151 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 29.4156 | 2-Sided | 95 | 19.1160 | 39.7151 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.2239 | Mean Difference (Final Values) | -6.3979 | 2-Sided | 95 | -16.7479 | 3.9521 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.4326 | Mean Difference (Final Values) | -4.1396 | 2-Sided | 95 | -14.5328 | 6.2526 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.7447 | Mean Difference (Final Values) | -1.7283 | 2-Sided | 95 | -12.1950 | 8.7383 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -30.4069 | 2-Sided | 95 | -40.6795 | -20.1343 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -28.1487 | 2-Sided | 95 | -38.4812 | -17.8161 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -25.7374 | 2-Sided | 95 | -36.1651 | -15.3096 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -35.8134 | 2-Sided | 95 | -45.9257 | -25.7012 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -33.5552 | 2-Sided | 95 | -43.7675 | -23.3429 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -31.1439 | 2-Sided | 95 | -41.4754 | -20.8124 | No | Superiority or Other |
| Emin |
|
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 25.9857 | 2-Sided | 95 | 20.6670 | 31.3043 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.4489 | Mean Difference (Final Values) | 2.0544 | 2-Sided | 95 | -3.2911 | 7.3998 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.8329 | Mean Difference (Final Values) | 0.5743 | 2-Sided | 95 | -4.7941 | 5.9427 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.5387 | Mean Difference (Final Values) | 1.6863 | 2-Sided | 95 | -3.7203 | 7.0929 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -22.8235 | 2-Sided | 95 | -28.1283 | -17.5187 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -24.3036 | 2-Sided | 95 | -29.6400 | -18.9672 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -23.1916 | 2-Sided | 95 | -28.5768 | -17.8064 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -23.9313 | 2-Sided | 95 | -29.1559 | -18.7066 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -25.4114 | 2-Sided | 95 | -30.6869 | -20.1358 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -24.2994 | 2-Sided | 95 | -29.6361 | -18.9626 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.5349 | Mean Difference (Final Values) | -1.4301 | 2-Sided | 95 | -5.9725 | 3.1123 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0001 | Mean Difference (Final Values) | -9.1367 | 2-Sided | 95 | -13.6684 | -4.6050 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.5637 | Mean Difference (Final Values) | 1.3357 | 2-Sided | 95 | -3.2244 | 5.8958 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.8612 | Mean Difference (Final Values) | 0.4065 | 2-Sided | 95 | -4.1779 | 4.9909 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.6954 | Mean Difference (Final Values) | 0.9175 | 2-Sided | 95 | -3.7022 | 5.5373 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.2287 | Mean Difference (Final Values) | 2.7658 | 2-Sided | 95 | -1.7552 | 7.2868 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.4267 | Mean Difference (Final Values) | 1.8366 | 2-Sided | 95 | -2.7158 | 6.3890 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.3140 | Mean Difference (Final Values) | 2.3476 | 2-Sided | 95 | -2.2429 | 6.9381 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 10.4724 | 2-Sided | 95 | 5.9992 | 14.9456 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 9.5432 | 2-Sided | 95 | 5.0320 | 14.0544 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 10.0542 | 2-Sided | 95 | 5.4940 | 14.6144 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 19.7284 | 2-Sided | 95 | 14.7131 | 24.7437 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.9348 | Mean Difference (Final Values) | 0.2088 | 2-Sided | 95 | -4.8289 | 5.2466 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.5009 | Mean Difference (Final Values) | -1.7271 | 2-Sided | 95 | -6.7841 | 3.3299 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.8975 | Mean Difference (Final Values) | -0.3325 | 2-Sided | 95 | -5.4245 | 4.7595 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -14.2640 | 2-Sided | 95 | -19.2660 | -9.2619 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -16.1999 | 2-Sided | 95 | -21.2294 | -11.1704 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -14.8053 | 2-Sided | 95 | -19.8822 | -9.7283 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -19.5195 | 2-Sided | 95 | -24.4361 | -14.6030 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -21.4555 | 2-Sided | 95 | -26.4230 | -16.4880 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -20.0609 | 2-Sided | 95 | -25.0872 | -15.0345 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 4.6706 | 2-Sided | 95 | 3.4066 | 5.9346 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.8184 | Mean Difference (Final Values) | 0.1478 | 2-Sided | 95 | -1.1217 | 1.4173 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.7324 | Mean Difference (Final Values) | 0.2211 | 2-Sided | 95 | -1.0540 | 1.4963 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.8844 | Mean Difference (Final Values) | 0.0946 | 2-Sided | 95 | -1.1898 | 1.3791 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -3.0156 | 2-Sided | 95 | -4.2754 | -1.7558 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -2.9423 | 2-Sided | 95 | -4.2101 | -1.6745 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -3.0688 | 2-Sided | 95 | -4.3484 | -1.7891 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -4.5228 | 2-Sided | 95 | -5.7651 | -3.2805 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -4.4495 | 2-Sided | 95 | -5.7031 | -3.1959 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -4.5760 | 2-Sided | 95 | -5.8438 | -3.3081 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 49.8771 | 2-Sided | 95 | 37.8247 | 61.9295 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.9248 | Mean Difference (Final Values) | -0.5797 | 2-Sided | 95 | -12.6918 | 11.5325 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.5857 | Mean Difference (Final Values) | -3.3632 | 2-Sided | 95 | -15.5264 | 8.8000 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.4768 | Mean Difference (Final Values) | 4.4225 | 2-Sided | 95 | -7.8270 | 16.6719 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -46.6594 | 2-Sided | 95 | -58.6804 | -34.6385 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -49.4430 | 2-Sided | 95 | -61.5346 | -37.3514 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -41.6573 | 2-Sided | 95 | -53.8600 | -29.4546 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -50.4567 | 2-Sided | 95 | -62.2925 | -38.6210 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -53.2403 | 2-Sided | 95 | -65.1923 | -41.2882 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -45.4546 | 2-Sided | 95 | -57.5459 | -33.3633 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 57.5013 | 2-Sided | 95 | 45.3036 | 69.6991 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.4129 | Mean Difference (Final Values) | -5.0913 | 2-Sided | 95 | -17.3421 | 7.1595 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.8488 | Mean Difference (Final Values) | -1.1893 | 2-Sided | 95 | -13.4954 | 11.1168 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.4086 | Mean Difference (Final Values) | 5.1995 | 2-Sided | 95 | -7.1963 | 17.5954 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -51.9363 | 2-Sided | 95 | -64.1108 | -39.7618 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -48.0343 | 2-Sided | 95 | -60.2801 | -35.7885 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -41.6455 | 2-Sided | 95 | -53.9964 | -29.2946 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -62.5926 | 2-Sided | 95 | -74.5881 | -50.5971 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -58.6906 | 2-Sided | 95 | -70.7965 | -46.5847 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -52.3018 | 2-Sided | 95 | -64.5427 | -40.0609 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 27.9971 | 2-Sided | 95 | 17.8247 | 38.1696 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.8254 | Mean Difference (Final Values) | -1.1425 | 2-Sided | 95 | -11.3591 | 9.0742 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.8858 | Mean Difference (Final Values) | 0.7470 | 2-Sided | 95 | -9.5075 | 11.0015 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.5128 | Mean Difference (Final Values) | 3.4279 | 2-Sided | 95 | -6.8972 | 13.7529 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0008 | Mean Difference (Final Values) | -17.6028 | 2-Sided | 95 | -27.7485 | -7.4572 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0028 | Mean Difference (Final Values) | -15.7134 | 2-Sided | 95 | -25.9136 | -5.5132 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0135 | Mean Difference (Final Values) | -13.0325 | 2-Sided | 95 | -23.3295 | -2.7355 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -29.1396 | 2-Sided | 95 | -39.1071 | -19.1721 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -27.2502 | 2-Sided | 95 | -37.3224 | -17.1780 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -24.5693 | 2-Sided | 95 | -34.7614 | -14.3772 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 3.5010 | 2-Sided | 95 | 2.8073 | 4.1948 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.3347 | Mean Difference (Final Values) | 0.3418 | 2-Sided | 95 | -0.3559 | 1.0396 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.3678 | Mean Difference (Final Values) | 0.3208 | 2-Sided | 95 | -0.3808 | 1.0225 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.9197 | Mean Difference (Final Values) | 0.0360 | 2-Sided | 95 | -0.6686 | 0.7406 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0099 | Mean Difference (Final Values) | -0.9117 | 2-Sided | 95 | -1.6013 | -0.2220 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0088 | Mean Difference (Final Values) | -0.9326 | 2-Sided | 95 | -1.6269 | -0.2384 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0008 | Mean Difference (Final Values) | -1.2175 | 2-Sided | 95 | -1.9171 | -0.5178 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -3.1592 | 2-Sided | 95 | -3.8380 | -2.4804 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -3.1802 | 2-Sided | 95 | -3.8656 | -2.4947 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -3.4650 | 2-Sided | 95 | -4.1583 | -2.7717 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 6.8983 | 2-Sided | 95 | 5.6799 | 8.1167 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.2917 | Mean Difference (Final Values) | 0.6545 | 2-Sided | 95 | -0.5676 | 1.8767 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.1738 | Mean Difference (Final Values) | 0.8489 | 2-Sided | 95 | -0.3784 | 2.0763 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.1373 | Mean Difference (Final Values) | 0.9372 | 2-Sided | 95 | -0.3024 | 2.1767 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -4.6397 | 2-Sided | 95 | -5.8537 | -3.4257 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -4.4453 | 2-Sided | 95 | -5.6662 | -3.2244 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -4.3571 | 2-Sided | 95 | -5.5887 | -3.1255 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -6.2437 | 2-Sided | 95 | -7.4397 | -5.0477 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -6.0493 | 2-Sided | 95 | -7.2568 | -4.8419 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -5.9611 | 2-Sided | 95 | -7.1812 | -4.7410 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -32.5724 | 2-Sided | 95 | -39.1073 | -26.0375 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.5685 | Mean Difference (Final Values) | 1.8966 | 2-Sided | 95 | -4.6607 | 8.4540 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.2848 | Mean Difference (Final Values) | -3.5761 | 2-Sided | 95 | -10.1590 | 3.0068 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.3440 | Mean Difference (Final Values) | -3.1754 | 2-Sided | 95 | -9.7855 | 3.4347 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 28.5172 | 2-Sided | 95 | 22.0454 | 34.9890 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 23.0445 | 2-Sided | 95 | 16.5383 | 29.5506 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 23.4452 | 2-Sided | 95 | 16.8772 | 30.0131 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 34.4690 | 2-Sided | 95 | 28.1136 | 40.8244 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 28.9963 | 2-Sided | 95 | 22.5734 | 35.4192 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 29.3970 | 2-Sided | 95 | 22.8946 | 35.8994 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 50.7222 | 2-Sided | 95 | 37.5038 | 63.9407 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.9174 | Mean Difference (Final Values) | -0.6987 | 2-Sided | 95 | -13.9815 | 12.5840 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.5002 | Mean Difference (Final Values) | -4.5629 | 2-Sided | 95 | -17.9006 | 8.7749 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.3482 | Mean Difference (Final Values) | 6.3982 | 2-Sided | 95 | -7.0337 | 19.8301 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -47.3031 | 2-Sided | 95 | -60.4869 | -34.1193 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -51.1672 | 2-Sided | 95 | -64.4276 | -37.9069 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -40.2062 | 2-Sided | 95 | -53.5890 | -26.8234 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -51.4210 | 2-Sided | 95 | -64.3974 | -38.4445 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -55.2851 | 2-Sided | 95 | -68.3904 | -42.1798 | No | Superiority or Other |
| Mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -44.3241 | 2-Sided | 95 | -57.5825 | -31.0656 | No | Superiority or Other |
| Benzodiazepines (n=23, 23, 25, 24, 22, 22) |
|
| Codeine/Morphine (n=20, 20, 23, 22, 20, 20) |
|
| THC (n=32, 33, 34, 33, 32, 31) |
|
| Pseudoephedrine (n=6, 6, 6, 6, 7, 5) |
|
| For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -51.5199 | 2-Sided | 95 | -67.2633 | -35.7765 | No | Superiority or Other |
| For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.4524 | Mean Difference (Final Values) | 6.0366 | 2-Sided | 95 | -9.7924 | 21.8657 | No | Superiority or Other |
| For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.7620 | Mean Difference (Final Values) | 2.4423 | 2-Sided | 95 | -13.4599 | 18.3446 | No | Superiority or Other |
| For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.9846 | Mean Difference (Final Values) | 0.1573 | 2-Sided | 95 | -15.8609 | 16.1754 | No | Superiority or Other |
| For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 52.4189 | 2-Sided | 95 | 36.7157 | 68.1221 | No | Superiority or Other |
| For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 48.8246 | 2-Sided | 95 | 33.0228 | 64.6264 | No | Superiority or Other |
| For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 46.5395 | 2-Sided | 95 | 30.5968 | 62.4823 | No | Superiority or Other |
| For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 57.5565 | 2-Sided | 95 | 42.0679 | 73.0451 | No | Superiority or Other |
| For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 53.9622 | 2-Sided | 95 | 38.3293 | 69.5952 | No | Superiority or Other |
| For placebo, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 51.6772 | 2-Sided | 95 | 35.8660 | 67.4884 | No | Superiority or Other |
| For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0003 | Mean Difference (Final Values) | 37.4454 | 2-Sided | 95 | 17.7051 | 57.1857 | No | Superiority or Other |
| For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 41.6714 | 2-Sided | 95 | 22.2888 | 61.0540 | No | Superiority or Other |
| For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0744 | Mean Difference (Final Values) | -17.7583 | 2-Sided | 95 | -37.2956 | 1.7789 | No | Superiority or Other |
| For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.3458 | Mean Difference (Final Values) | -9.5551 | 2-Sided | 95 | -29.5573 | 10.4471 | No | Superiority or Other |
| For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.9375 | Mean Difference (Final Values) | 0.7920 | 2-Sided | 95 | -19.1777 | 20.7616 | No | Superiority or Other |
| For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -55.2037 | 2-Sided | 95 | -74.8113 | -35.5961 | No | Superiority or Other |
| For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -47.0005 | 2-Sided | 95 | -67.0020 | -26.9989 | No | Superiority or Other |
| For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0004 | Mean Difference (Final Values) | -36.6534 | 2-Sided | 95 | -56.7246 | -16.5822 | No | Superiority or Other |
| For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -59.4297 | 2-Sided | 95 | -78.5162 | -40.3433 | No | Superiority or Other |
| For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -51.2265 | 2-Sided | 95 | -70.8131 | -31.6399 | No | Superiority or Other |
| For benzodiazepines, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0001 | Mean Difference (Final Values) | -40.8794 | 2-Sided | 95 | -60.4726 | -21.2862 | No | Superiority or Other |
| For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0102 | Mean Difference (Final Values) | 23.5197 | 2-Sided | 95 | 5.7096 | 41.3298 | No | Superiority or Other |
| For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0021 | Mean Difference (Final Values) | 27.7321 | 2-Sided | 95 | 10.3632 | 45.1011 | No | Superiority or Other |
| For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.5935 | Mean Difference (Final Values) | -4.7334 | 2-Sided | 95 | -22.2807 | 12.8140 | No | Superiority or Other |
| For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.6945 | Mean Difference (Final Values) | 3.5486 | 2-Sided | 95 | -14.3397 | 21.4370 | No | Superiority or Other |
| For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.4177 | Mean Difference (Final Values) | 7.2936 | 2-Sided | 95 | -10.4975 | 25.0847 | No | Superiority or Other |
| For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0019 | Mean Difference (Final Values) | -28.2531 | 2-Sided | 95 | -45.8020 | -10.7042 | No | Superiority or Other |
| For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0299 | Mean Difference (Final Values) | -19.9711 | 2-Sided | 95 | -37.9541 | -1.9880 | No | Superiority or Other |
| For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0759 | Mean Difference (Final Values) | -16.2261 | 2-Sided | 95 | -34.1785 | 1.7264 | No | Superiority or Other |
| For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0002 | Mean Difference (Final Values) | -32.4655 | 2-Sided | 95 | -49.2278 | -15.7032 | No | Superiority or Other |
| For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0069 | Mean Difference (Final Values) | -24.1835 | 2-Sided | 95 | -41.5832 | -6.7838 | No | Superiority or Other |
| For codeine/morphine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0222 | Mean Difference (Final Values) | -20.4385 | 2-Sided | 95 | -37.8861 | -2.9910 | No | Superiority or Other |
| For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0002 | Mean Difference (Final Values) | 24.5890 | 2-Sided | 95 | 12.0126 | 37.1654 | No | Superiority or Other |
| For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 29.1100 | 2-Sided | 95 | 16.4903 | 41.7298 | No | Superiority or Other |
| For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.6809 | Mean Difference (Final Values) | 2.6428 | 2-Sided | 95 | -10.0309 | 15.3165 | No | Superiority or Other |
| For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.6067 | Mean Difference (Final Values) | -3.3215 | 2-Sided | 95 | -16.0415 | 9.3985 | No | Superiority or Other |
| For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.3999 | Mean Difference (Final Values) | 5.4722 | 2-Sided | 95 | -7.3350 | 18.2795 | No | Superiority or Other |
| For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0007 | Mean Difference (Final Values) | -21.9461 | 2-Sided | 95 | -34.5327 | -9.3596 | No | Superiority or Other |
| For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -27.9105 | 2-Sided | 95 | -40.5640 | -15.2570 | No | Superiority or Other |
| For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0036 | Mean Difference (Final Values) | -19.1168 | 2-Sided | 95 | -31.8907 | -6.3428 | No | Superiority or Other |
| For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -26.4672 | 2-Sided | 95 | -38.8298 | -14.1046 | No | Superiority or Other |
| For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -32.4315 | 2-Sided | 95 | -44.9250 | -19.9380 | No | Superiority or Other |
| For THC, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0003 | Mean Difference (Final Values) | -23.6378 | 2-Sided | 95 | -36.2802 | -10.9954 | No | Superiority or Other |
| For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.9728 | Mean Difference (Final Values) | 0.6675 | 2-Sided | 95 | -39.7080 | 41.0430 | No | Superiority or Other |
| For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0246 | Mean Difference (Final Values) | 42.7977 | 2-Sided | 95 | 6.1059 | 79.4894 | No | Superiority or Other |
| For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.7068 | Mean Difference (Final Values) | 7.5411 | 2-Sided | 95 | -33.7850 | 48.8672 | No | Superiority or Other |
| For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.5492 | Mean Difference (Final Values) | 10.7069 | 2-Sided | 95 | -26.0358 | 47.4496 | No | Superiority or Other |
| For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.5899 | Mean Difference (Final Values) | 11.1248 | 2-Sided | 95 | -31.3098 | 53.5595 | No | Superiority or Other |
| For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.6998 | Mean Difference (Final Values) | 6.8736 | 2-Sided | 95 | -29.8691 | 43.6163 | No | Superiority or Other |
| For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.6187 | Mean Difference (Final Values) | 10.0394 | 2-Sided | 95 | -31.4818 | 51.5606 | No | Superiority or Other |
| For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.5863 | Mean Difference (Final Values) | 10.4573 | 2-Sided | 95 | -29.0355 | 49.9502 | No | Superiority or Other |
| For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0832 | Mean Difference (Final Values) | -35.2566 | 2-Sided | 95 | -75.6080 | 5.0948 | No | Superiority or Other |
| For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0827 | Mean Difference (Final Values) | -32.0907 | 2-Sided | 95 | -68.7519 | 4.5704 | No | Superiority or Other |
| For pseudoephedrine, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.1386 | Mean Difference (Final Values) | -31.6728 | 2-Sided | 95 | -74.5352 | 11.1895 | No | Superiority or Other |
| Emin |
|
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0017 | Mean Difference (Final Values) | 0.8444 | 2-Sided | 95 | 0.3238 | 1.3650 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.4305 | Mean Difference (Final Values) | 0.2093 | 2-Sided | 95 | -0.3141 | 0.7327 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.6517 | Mean Difference (Final Values) | 0.1206 | 2-Sided | 95 | -0.4064 | 0.6476 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.8892 | Mean Difference (Final Values) | -0.0374 | 2-Sided | 95 | -0.5666 | 0.4919 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.5576 | Mean Difference (Final Values) | -0.1544 | 2-Sided | 95 | -0.6737 | 0.3649 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.3594 | Mean Difference (Final Values) | -0.2431 | 2-Sided | 95 | -0.7658 | 0.2796 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.1355 | Mean Difference (Final Values) | -0.4011 | 2-Sided | 95 | -0.9291 | 0.1270 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0153 | Mean Difference (Final Values) | -0.6351 | 2-Sided | 95 | -1.1466 | -0.1236 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0065 | Mean Difference (Final Values) | -0.7238 | 2-Sided | 95 | -1.2418 | -0.2059 | No | Superiority or Other |
| For Emax, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.0011 | Mean Difference (Final Values) | -0.8818 | 2-Sided | 95 | -1.4042 | -0.3594 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -2.1614 | 2-Sided | 95 | -2.9373 | -1.3856 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | -3.0336 | 2-Sided | 95 | -3.8085 | -2.2587 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.4804 | Mean Difference (Final Values) | -0.2791 | 2-Sided | 95 | -1.0586 | 0.5004 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.9519 | Mean Difference (Final Values) | 0.0240 | 2-Sided | 95 | -0.7608 | 0.8087 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | 0.2152 | Mean Difference (Final Values) | -0.4970 | 2-Sided | 95 | -1.2860 | 0.2921 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 1.8824 | 2-Sided | 95 | 1.1094 | 2.6553 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 2.1854 | 2-Sided | 95 | 1.4070 | 2.9638 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 1.6645 | 2-Sided | 95 | 0.8786 | 2.4503 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 2.7545 | 2-Sided | 95 | 1.9912 | 3.5179 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 3.0576 | 2-Sided | 95 | 2.2858 | 3.8294 | No | Superiority or Other |
| For Emin, mixed-effect model was used which included treatment, period and sequence as fixed effects, baseline measurement as covariate where applicable, and participant nested within sequence as random effect. The estimates of adjusted mean differences and corresponding 95% CI were obtained from the model. | Mixed Models Analysis | Mixed-effect model was implemented with REML estimation method and Kenward-Roger degrees of freedom algorithm. | <0.0001 | Mean Difference (Final Values) | 2.5366 | 2-Sided | 95 | 1.7578 | 3.3155 | No | Superiority or Other |