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Phase 4, double-blind, placebo-controlled, four treatment, four sequence crossover study comparing simulated driving performance, daytime sedation and cognition in healthy volunteers administered therapeutic doses of Gralise® (Treatment A), Neurontin® (Treatment B), Lyrica® (Treatment C) and placebo (Treatment D). All doses were administered under fed conditions.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Gralise® (gabapentin) | Active Comparator | Gralise® 3 x 600 mg tablets (1800 mg total dose) administered once daily at 7:00 pm on Day 1 and Day 2 with one placebo capsule matching the over-encapsulation of doses of Neurontin® and Lyrica®. At other dosing times, treatment consisted of 3 placebo tablets matching the appearance of Gralise® and 1 placebo capsule. |
|
| Neurontin® (gabapentin) | Active Comparator | Neurontin® 1 x 600 mg film-coated tablet administered 3 times daily at 7:00 pm on Day 1, at 8:00 am, 2:00 pm and 8:00 pm on Day 2 and at 8:00 a.m. on Day 3. Each dose of Neurontin® was over-encapsulated and administered with 3 placebo tablets matching the appearance of Gralise®. |
|
| Lyrica® (pregabalin) | Active Comparator | Lyrica® 1 x 150 mg capsule administered 2 times daily at 7:00 pm on Day 1, at 8:00 am and 8:00 pm on Day 2 and at 8:00 a.m. on Day 3. Each dose of Lyrica® was over-encapsulated and administered with 3 placebo tablets matching the appearance of Gralise®. |
|
| Placebo (sugar pill) | Placebo Comparator | Each dose consisted of 3 placebo tablets matching the appearance of Gralise® and 1 placebo capsule matching the over-encapsulation of doses of Neurontin® and Lyrica®. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Gabapentin | Drug |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the "Standard Deviation of the Lateral Position" (SDLP) Measured on the Driving Simulator Between Gralise® and Neurontin® | SDLP (feet): This is a measurement of change from maintaining the normal driving position in the lane over time and / or distance. | Baseline and Hour 3 on Day 3 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the "Standard Deviation of the Lateral Position" (SDLP) Measured on the Driving Simulator Between Gralise® and Lyrica® | SDLP (feet): This is a measurement of change from maintaining the normal driving position in the lane over time and / or distance. | Baseline and Hour 3 on Day 3 |
| Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Cognitive Evaluation of Cogstate - Detection Task (DET) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Head of R&D | Depomed | Study Director |
Not provided
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29671676 | Derived | Schmidt P, Rao S. Effects of gabapentin, pregabalin and gastroretentive gabapentin on simulated driving, daytime sedation and cognition. Pain Manag. 2018 Jul 1;8(4):297-306. doi: 10.2217/pmt-2018-0005. Epub 2018 Apr 19. |
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A total of 32 healthy subjects enrolled in this crossover study. Each subject was randomly assigned to 1 out of 4 treatment sequences.
Abbreviations:
Gral = Gralise®; Neur = Neurontin®; Lyr = Lyrica®; Plbo = Placebo.
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| ID | Title | Description |
|---|---|---|
| FG000 | Gral First, Then Neur, Lyr, and Plbo | Gralise® (gabapentin) 3 x 600 mg tablets (1800 mg total): Dosed once daily in the evening on Day 1 and Day 2. Neurontin® (gabapentin) 1 x 600 mg film-coated tablet: Dosed 3 times daily starting in the evening on Day 1, in the morning, afternoon, and evening on Day 2, and in the morning on Day 3. Lyrica® (pregabalin) 1 x 150 mg capsule: Dosed 2 times daily starting in the evening on Day 1, in the morning and evening on Day 2, and in the morning on Day 3. Placebo (sugar pill): Three (3) placebo tablets matching the appearance of Gralise® & 1 placebo capsule matching the over-encapsulation of doses of Neurontin® & Lyrica®. All treatments were administered following a meal. Each treatment period was separated by a 7-day washout interval. |
| FG001 | Neur First, Then Plbo, Gral, and Lyr | Neurontin® (gabapentin) 1 x 600 mg film-coated tablet: Dosed 3 times daily starting in the evening on Day 1, in the morning, afternoon, and evening on Day 2, and in the morning on Day 3. Placebo (sugar pill): Three (3) placebo tablets matching the appearance of Gralise® & 1 placebo capsule matching the over-encapsulation of doses of Neurontin® & Lyrica®. Gralise® (gabapentin) 3 x 600 mg tablets (1800 mg total): Dosed once daily in the evening on Day 1 and Day 2. Lyrica® (pregabalin) 1 x 150 mg capsule: Dosed 2 times daily starting in the evening on Day 1, in the morning and evening on Day 2, and in the morning on Day 3. All treatments were administered following a meal. Each treatment period was separated by a 7-day washout interval. |
| FG002 | Lyr First, Then Gral, Plbo, and Neur | Lyrica® (pregabalin) 1 x 150 mg capsule: Dosed 2 times daily starting in the evening on Day 1, in the morning and evening on Day 2, and in the morning on Day 3. Gralise® (gabapentin) 3 x 600 mg tablets (1800 mg total): Dosed once daily in the evening on Day 1 and Day 2. Placebo (sugar pill): Three (3) placebo tablets matching the appearance of Gralise® & 1 placebo capsule matching the over-encapsulation of doses of Neurontin® & Lyrica®. Neurontin® (gabapentin) 1 x 600 mg film-coated tablet: Dosed 3 times daily starting in the evening on Day 1, in the morning, afternoon, and evening on Day 2, and in the morning on Day 3. All treatments were administered following a meal. Each treatment period was separated by a 7-day washout interval. |
| FG003 | Plbo First, Then Lyr, Neur, and Gral | Placebo (sugar pill): Three (3) placebo tablets matching the appearance of Gralise® & 1 placebo capsule matching the over-encapsulation of doses of Neurontin® & Lyrica®. Lyrica® (pregabalin) 1 x 150 mg capsule: Dosed 2 times daily starting in the evening on Day 1, in the morning and evening on Day 2, and in the morning on Day 3. Neurontin® (gabapentin) 1 x 600 mg film-coated tablet: Dosed 3 times daily starting in the evening on Day 1, in the morning, afternoon, and evening on Day 2, and in the morning on Day 3. Gralise® (gabapentin) 3 x 600 mg tablets (1800 mg total): Dosed once daily in the evening on Day 1 and Day 2. All treatments were administered following a meal. Each treatment period was separated by a 7-day washout interval. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Gral First, Then Neur, Lyr, and Plbo | Gralise® (gabapentin) 3 x 600 mg tablets (1800 mg total): Dosed once daily in the evening on Day 1 and Day 2. Neurontin® (gabapentin) 1 x 600 mg film-coated tablet: Dosed 3 times daily starting in the evening on Day 1, in the morning, afternoon, and evening on Day 2, and in the morning on Day 3. Lyrica® (pregabalin) 1 x 150 mg capsule: Dosed 2 times daily starting in the evening on Day 1, in the morning and evening on Day 2, and in the morning on Day 3. Placebo (sugar pill): Three (3) placebo tablets matching the appearance of Gralise® & 1 placebo capsule matching the over-encapsulation of doses of Neurontin® & Lyrica®. All treatments were administered following a meal. Each treatment period was separated by a 7-day washout interval. |
| 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 | Change From Baseline in the "Standard Deviation of the Lateral Position" (SDLP) Measured on the Driving Simulator Between Gralise® and Neurontin® | SDLP (feet): This is a measurement of change from maintaining the normal driving position in the lane over time and / or distance. | The above is the only Primary Outcome Measure (comparing the SDLP between Gralise® and Neurontin®). | Posted | Least Squares Mean | Standard Error | feet | Baseline and Hour 3 on Day 3 |
|
7 weeks
Adverse Events were reported from the signed informed consent to 30 days after the last dose of study drug.
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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 | Gralise® (Gabapentin) | Gralise® (gabapentin) 3 x 600 mg tablets (1800 mg total): Dosed once daily in the evening on Day 1 and Day 2. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Somnolence | Nervous system disorders |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Operations | Depomed | 510-744-8000 | clinicaltrials@depomed.com |
Not provided
| ID | Term |
|---|---|
| D000077206 | Gabapentin |
| D000069583 | Pregabalin |
| D000073893 | Sugars |
| ID | Term |
|---|---|
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D005680 | gamma-Aminobutyric Acid |
| D000613 | Aminobutyrates |
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Not provided
| Pregabalin |
| Drug |
|
|
| Placebo | Other |
|
|
Cogstate - Detection Task (DET) is a simple reaction time test of Psychomotor Function. Higher change from baseline means better performance. |
| Baseline and Hour 3 on Day 3 |
| Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Cognitive Evaluation of Cogstate - Groton Maze Learning Test (GMLT). | Cogstate - The Groton Maze Learning test is a measure Executive Function. Total number of errors made while attempting to learn the same hidden pathway across the consecutive learning trials performed at a single assessment. Lower score means better performance. Higher change from baseline means better performance. | Baseline and Hour 3 on Day 3 |
| Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Cognitive Evaluation of Cogstate - Identification Task (IDN). | Cogstate - Identification Task (IDN) assesses Attention. Score is speed of performance (mean of the log10 transformed reaction times for correct responses). Lower score (quicker speed) is better performance. Higher change from baseline means better performance. | Baseline and Hour 3 on Day 3 |
| Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Cognitive Evaluation of Cogstate - International Shopping List Test (ISL) | Cogstate - International Shopping List (ISL) test is a measure of verbal learning and uses a well-validated list-learning paradigm. Total number of correct responses remembering the word list on three consecutive trials at a single assessment. Higher score is better performance. Higher change from baseline means better performance. | Baseline and Hour 3 on Day 3 |
| Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Cognitive Evaluation of Cogstate - One Card Learning (OCLT). | Cogstate - The One Card Learning Test (OCLT) is a measure of visual learning and uses a well-validated pattern separation paradigm with playing card stimuli. Higher Score is better performance. Higher change from baseline means better performance. | Baseline and Hour 3 on Day 3 |
| Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Sedation Evaluation - Karolinska Sleepiness Scale (KSS). | Scale: 1-9, 1=extremely alert, 9 = very sleepy, great effort to keep awake, fighting sleep | Baseline and Hour 3 on Day 3 |
| Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Sedation Evaluation - Portland Neurotoxicity Scale (PNS). | Portland Neurotoxicity Scale (PNS) comprises 15 questions measured on a 10-point scale. [1=No problem, 2, 3, 4, 5=Often a problem, 6, 7, 8, 9, 10=Severe problem] in 16 categories. Each question was analyzed and is presented in the same way as the primary endpoints. | Baseline and Hour 3 on Day 3 |
| Change From Baseline Between Gralise® and Neurontin® in the Driving Simulator - Standard Deviation of Vehicle Speed (SDVS). | Miles per Hour (mph) | Baseline and Hour 3 on Day 3 |
| Change From Baseline Between Gralise® and Lyrica® in the Driving Simulator - Standard Deviation of Vehicle Speed (SDVS). | Miles per Hour (mph) | Baseline and Hour 3 on Day 3 |
| To Compare the Relative Safety and Tolerability of Gralise®, Neurontin®, and Lyrica®. |
| Screening to 1 week after Period 4 discharge |
| BG001 | Neur First, Then Plbo, Gral, and Lyr | Neurontin® (gabapentin) 1 x 600 mg film-coated tablet: Dosed 3 times daily starting in the evening on Day 1, in the morning, afternoon, and evening on Day 2, and in the morning on Day 3. Placebo (sugar pill): Three (3) placebo tablets matching the appearance of Gralise® & 1 placebo capsule matching the over-encapsulation of doses of Neurontin® & Lyrica®. Gralise® (gabapentin) 3 x 600 mg tablets (1800 mg total): Dosed once daily in the evening on Day 1 and Day 2. Lyrica® (pregabalin) 1 x 150 mg capsule: Dosed 2 times daily starting in the evening on Day 1, in the morning and evening on Day 2, and in the morning on Day 3. All treatments were administered following a meal. Each treatment period was separated by a 7-day washout interval. |
| BG002 | Lyr First, Then Gral, Plbo, and Neur | Lyrica® (pregabalin) 1 x 150 mg capsule: Dosed 2 times daily starting in the evening on Day 1, in the morning and evening on Day 2, and in the morning on Day 3. Gralise® (gabapentin) 3 x 600 mg tablets (1800 mg total): Dosed once daily in the evening on Day 1 and Day 2. Placebo (sugar pill): Three (3) placebo tablets matching the appearance of Gralise® & 1 placebo capsule matching the over-encapsulation of doses of Neurontin® & Lyrica®. Neurontin® (gabapentin) 1 x 600 mg film-coated tablet: Dosed 3 times daily starting in the evening on Day 1, in the morning, afternoon, and evening on Day 2, and in the morning on Day 3. All treatments were administered following a meal. Each treatment period was separated by a 7-day washout interval. |
| BG003 | Plbo First, Then Lyr, Neur, and Gral | Placebo (sugar pill): Three (3) placebo tablets matching the appearance of Gralise® & 1 placebo capsule matching the over-encapsulation of doses of Neurontin® & Lyrica®. Lyrica® (pregabalin) 1 x 150 mg capsule: Dosed 2 times daily starting in the evening on Day 1, in the morning and evening on Day 2, and in the morning on Day 3. Neurontin® (gabapentin) 1 x 600 mg film-coated tablet: Dosed 3 times daily starting in the evening on Day 1, in the morning, afternoon, and evening on Day 2, and in the morning on Day 3. Gralise® (gabapentin) 3 x 600 mg tablets (1800 mg total): Dosed once daily in the evening on Day 1 and Day 2. All treatments were administered following a meal. Each treatment period was separated by a 7-day washout interval. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Neurontin® (gabapentin) 1 x 600 mg film-coated tablet: Dosed 3 times daily starting in the evening on Day 1, in the morning, afternoon, and evening on Day 2, and in the morning on Day 3.
| OG002 | Placebo | Each dose consisted of 3 placebo tablets matching the appearance of Gralise® and 1 placebo capsule matching the over-encapsulation of doses of Neurontin® and Lyrica®: Dosed 3 times daily starting in the evening on Day 1, in the morning, afternoon, and evening on Day 2, and in the morning on Day 3. |
|
|
|
| Secondary | Change From Baseline in the "Standard Deviation of the Lateral Position" (SDLP) Measured on the Driving Simulator Between Gralise® and Lyrica® | SDLP (feet): This is a measurement of change from maintaining the normal driving position in the lane over time and / or distance. | The above is a Secondary Outcome Measure (comparing the SDLP between Gralise® and Lyrica®). | Posted | Least Squares Mean | Standard Error | feet | Baseline and Hour 3 on Day 3 |
|
|
|
|
| Secondary | Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Cognitive Evaluation of Cogstate - Detection Task (DET) | Cogstate - Detection Task (DET) is a simple reaction time test of Psychomotor Function. Higher change from baseline means better performance. | Posted | Least Squares Mean | Standard Error | msec | Baseline and Hour 3 on Day 3 |
|
|
|
|
| Secondary | Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Cognitive Evaluation of Cogstate - Groton Maze Learning Test (GMLT). | Cogstate - The Groton Maze Learning test is a measure Executive Function. Total number of errors made while attempting to learn the same hidden pathway across the consecutive learning trials performed at a single assessment. Lower score means better performance. Higher change from baseline means better performance. | Posted | Least Squares Mean | Standard Error | Number of errors on test | Baseline and Hour 3 on Day 3 |
|
|
|
|
| Secondary | Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Cognitive Evaluation of Cogstate - Identification Task (IDN). | Cogstate - Identification Task (IDN) assesses Attention. Score is speed of performance (mean of the log10 transformed reaction times for correct responses). Lower score (quicker speed) is better performance. Higher change from baseline means better performance. | Posted | Least Squares Mean | Standard Error | Score on Scale | Baseline and Hour 3 on Day 3 |
|
|
|
|
| Secondary | Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Cognitive Evaluation of Cogstate - International Shopping List Test (ISL) | Cogstate - International Shopping List (ISL) test is a measure of verbal learning and uses a well-validated list-learning paradigm. Total number of correct responses remembering the word list on three consecutive trials at a single assessment. Higher score is better performance. Higher change from baseline means better performance. | Posted | Least Squares Mean | Standard Error | Score on Scale | Baseline and Hour 3 on Day 3 |
|
|
|
|
| Secondary | Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Cognitive Evaluation of Cogstate - One Card Learning (OCLT). | Cogstate - The One Card Learning Test (OCLT) is a measure of visual learning and uses a well-validated pattern separation paradigm with playing card stimuli. Higher Score is better performance. Higher change from baseline means better performance. | Posted | Least Squares Mean | Standard Error | Score on Scale | Baseline and Hour 3 on Day 3 |
|
|
|
|
| Secondary | Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Sedation Evaluation - Karolinska Sleepiness Scale (KSS). | Scale: 1-9, 1=extremely alert, 9 = very sleepy, great effort to keep awake, fighting sleep | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline and Hour 3 on Day 3 |
|
|
|
|
| Secondary | Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Sedation Evaluation - Portland Neurotoxicity Scale (PNS). | Portland Neurotoxicity Scale (PNS) comprises 15 questions measured on a 10-point scale. [1=No problem, 2, 3, 4, 5=Often a problem, 6, 7, 8, 9, 10=Severe problem] in 16 categories. Each question was analyzed and is presented in the same way as the primary endpoints. | Full Analysis Set | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline and Hour 3 on Day 3 |
|
|
|
|
| Secondary | Change From Baseline Between Gralise® and Neurontin® in the Driving Simulator - Standard Deviation of Vehicle Speed (SDVS). | Miles per Hour (mph) | Full Analysis Set | Posted | Least Squares Mean | Standard Error | mph | Baseline and Hour 3 on Day 3 |
|
|
|
|
| Secondary | Change From Baseline Between Gralise® and Lyrica® in the Driving Simulator - Standard Deviation of Vehicle Speed (SDVS). | Miles per Hour (mph) | Full Analysis Set | Posted | Least Squares Mean | Standard Error | mph | Baseline and Hour 3 on Day 3 |
|
|
|
|
| Secondary | To Compare the Relative Safety and Tolerability of Gralise®, Neurontin®, and Lyrica®. |
| Posted | Number | participants | No | Screening to 1 week after Period 4 discharge |
|
|
|
| 0 |
| 28 |
| 6 |
| 28 |
| EG001 | Neurontin® (Gabapentin) | Neurontin® (gabapentin) 1 x 600 mg film-coated tablet: Dosed 3 times daily starting in the evening on Day 1, in the morning, afternoon, and evening on Day 2, and in the morning on Day 3. | 0 | 31 | 11 | 31 |
| EG002 | Lyrica® (Pregabalin) | Lyrica® (pregabalin) 1 x 150 mg capsule: Dosed 2 times daily starting in the evening on Day 1, in the morning and evening on Day 2, and in the morning on Day 3. | 0 | 31 | 14 | 31 |
| EG003 | Placebo (Sugar Pill) | Placebo (sugar pill): Three (3) placebo tablets matching the appearance of Gralise® & 1 placebo capsule matching the over-encapsulation of doses of Neurontin® & Lyrica®. | 0 | 30 | 2 | 30 |
| Dizziness | Nervous system disorders |
|
| Headache | Nervous system disorders |
|
| Euphoric mood | Psychiatric disorders |
|
The PI agrees that sponsor shall have the right to the first publication of the study results which is intended to be a joint, multi-center publication. Following the first publication, the PI may publish study data or results, provided however PI submits the proposed publication to sponsor for review at least 60 days prior to the date of the proposed publication. Sponsor may remove any information that is considered confidential and / or proprietary other than study data.
| D002087 |
| Butyrates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D003509 | Cyclohexanecarboxylic Acids |
| D000146 | Acids, Carbocyclic |
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D002241 | Carbohydrates |
| ANOVA |
Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. |
| 0.0611 |
| Mean Difference (Net) |
| 0.120 |
| Standard Error of the Mean |
| 0.06 |
| 2-Sided |
| 95 |
| -0.006 |
| 0.245 |
SE of difference estimated by dividing width of 95% CI by 4. |
| Superiority |
| ANCOVA |
Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. |
| 0.1673 |
| Mean Difference (Net) |
| 0.02 |
| Standard Error of the Mean |
| 0.0125 |
| 2-Sided |
| 95 |
| -0.01 |
| 0.04 |
SE of difference estimated by dividing width of 95% CI by 4. |
| Superiority |
| ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.6208 | Mean Difference (Net) | 0.01 | Standard Error of the Mean | 0.0125 | 2-Sided | 95 | -0.02 | 0.03 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| ANOVA |
Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. |
| 0.9277 |
| Mean Difference (Net) |
| 0.24 |
| Standard Error of the Mean |
| 2.61 |
| 2-Sided |
| 95 |
| -4.97 |
| 5.45 |
SE of difference estimated by dividing width of 95% CI by 4. |
| Superiority |
| ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.1587 | Mean Difference (Net) | -3.73 | 2-Sided | 95 | -8.94 | 1.49 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| ANOVA |
Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. |
| 0.9048 |
| Mean Difference (Net) |
| -0.00 |
| Standard Error of the Mean |
| 0.01 |
| 2-Sided |
| 95 |
| -0.02 |
| 0.02 |
SE of difference estimated by dividing width of 95% CI by 4. |
| Superiority |
| ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.3262 | Mean Difference (Net) | -0.01 | Standard Error of the Mean | 0.01 | 2-Sided | 95 | -0.03 | 0.01 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| ANOVA |
Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. |
| 0.7057 |
| Mean Difference (Net) |
| 0.33 |
| Standard Error of the Mean |
| 0.865 |
| 2-Sided |
| 95 |
| -1.40 |
| 2.06 |
SE of difference estimated by dividing width of 95% CI by 4. |
| Superiority |
| ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.6741 | Mean Difference (Net) | 0.37 | Standard Error of the Mean | 0.865 | 2-Sided | 95 | -1.36 | 2.10 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| ANOVA |
Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. |
| 0.5183 |
| Mean Difference (Net) |
| 0.01 |
| Standard Error of the Mean |
| 0.0175 |
| 2-Sided |
| 95 |
| -0.02 |
| 0.05 |
SE of difference estimated by dividing width of 95% CI by 4. |
| Superiority |
| ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.5084 | Mean Difference (Net) | -0.01 | Standard Error of the Mean | 0.0175 | 2-Sided | 95 | -0.05 | 0.02 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| ANOVA |
Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. |
| 0.7634 |
| Mean Difference (Net) |
| -0.094 |
| Standard Error of the Mean |
| 0.309 |
| 2-Sided |
| 95 |
| -0.711 |
| 0.523 |
SE of difference estimated by dividing width of 95% CI by 4. |
| Superiority |
| ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.1041 | Mean Difference (Net) | 0.510 | Standard Error of the Mean | 0.309 | 2-Sided | 95 | -0.107 | 1.127 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
|
| Energy Level (get up and go) |
|
|
| Memory (ability to remember people, places, or thi |
|
|
| Walking (balance) |
|
|
| Interest (in activities) |
|
|
| Coordination |
|
|
| Tremor (shakiness) |
|
|
| Concentration (ability to concentrate on a task) |
|
|
| Speech (slurring words) |
|
|
| Forgetfulness |
|
|
| Sleepiness (fatigue, sedation, tiredness) |
|
|
| Moodiness |
|
|
| Alertness |
|
|
| Attention Span |
|
|
| Motivation |
|
|
|
Energy Level |
| ANOVA |
Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. |
| 0.4120 |
| Mean Difference (Net) |
| -0.157 |
| Standard Error of the Mean |
| 0.19 |
| 2-Sided |
| 95 |
| -0.536 |
| 0.222 |
SE of difference estimated by dividing width of 95% CI by 4. |
| Superiority |
| Memory | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.7724 | Mean Difference (Net) | -0.046 | Standard Error of the Mean | 0.16 | 2-Sided | 95 | -0.362 | 0.270 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Walking Balance | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.4255 | Mean Difference (Net) | -0.121 | Standard Error of the Mean | 0.15 | 2-Sided | 95 | -0.423 | 0.180 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Interest in activities | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.8925 | Mean Difference (Net) | 0.017 | Standard Error of the Mean | 0.12 | 2-Sided | 95 | -0.229 | 0.262 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Coordination | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.1293 | Mean Difference (Net) | -0.212 | Standard Error of the Mean | 0.14 | 2-Sided | 95 | -0.487 | 0.063 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Tremor | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.0304 | Mean Difference (Net) | -0.140 | Standard Error of the Mean | 0.06 | 2-Sided | 95 | -0.266 | -0.014 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Concentration | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.5811 | Mean Difference (Net) | -0.084 | Standard Error of the Mean | 0.15 | 2-Sided | 95 | -0.384 | 0.217 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Speech | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.1144 | Mean Difference (Net) | -0.098 | Standard Error of the Mean | 0.06 | 2-Sided | 95 | -0.220 | 0.024 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Forgetfulness | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.3774 | Mean Difference (Net) | -0.109 | Standard Error of the Mean | 0.12 | 2-Sided | 95 | -0.352 | 0.135 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Sleepiness | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.8658 | Mean Difference (Net) | 0.057 | Standard Error of the Mean | 0.34 | 2-Sided | 95 | -0.613 | 0.727 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Moodiness | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.8543 | Mean Difference (Net) | 0.018 | Standard Error of the Mean | 0.10 | 2-Sided | 95 | -0.179 | 0.216 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Alertness | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.4294 | Mean Difference (Net) | -0.153 | Standard Error of the Mean | 0.19 | 2-Sided | 95 | -0.537 | 0.231 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Attention Span | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.3613 | Mean Difference (Net) | -0.113 | Standard Error of the Mean | 0.12 | 2-Sided | 95 | -0.357 | 0.132 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Motivation | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.7201 | Mean Difference (Net) | -0.047 | Standard Error of the Mean | 0.13 | 2-Sided | 95 | -0.305 | 0.212 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Vision | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.0767 | Mean Difference (Net) | -0.213 | Standard Error of the Mean | 0.12 | 2-Sided | 95 | -0.448 | 0.023 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Energy Level | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.2618 | Mean Difference (Net) | -0.216 | Standard Error of the Mean | 0.19 | 2-Sided | 95 | -0.597 | 0.165 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Memory | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.7633 | Mean Difference (Net) | -0.048 | Standard Error of the Mean | 0.16 | 2-Sided | 95 | -0.366 | 0.269 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Walking Balance | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.1968 | Mean Difference (Net) | -0.198 | Standard Error of the Mean | 0.15 | 2-Sided | 95 | -0.502 | 0.105 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Interest in Activities | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.6891 | Mean Difference (Net) | -0.050 | Standard Error of the Mean | 0.12 | 2-Sided | 95 | -0.296 | 0.197 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Coordination | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.2229 | Mean Difference (Net) | -0.171 | Standard Error of the Mean | 0.14 | 2-Sided | 95 | -0.447 | 0.106 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Tremor | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.2591 | Mean Difference (Net) | -0.072 | Standard Error of the Mean | 0.06 | 2-Sided | 95 | -0.197 | 0.054 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Concentration | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.7099 | Mean Difference (Net) | -0.057 | Standard Error of the Mean | 0.15 | 2-Sided | 95 | -0.359 | 0.246 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Speech | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.6215 | Mean Difference (Net) | -0.031 | Standard Error of the Mean | 0.06 | 2-Sided | 95 | -0.154 | 0.092 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Forgetfulness | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.6422 | Mean Difference (Net) | -0.057 | Standard Error of the Mean | 0.12 | 2-Sided | 95 | -0.302 | 0.187 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Sleepiness | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.1574 | Mean Difference (Net) | -0.483 | Standard Error of the Mean | 0.34 | 2-Sided | 95 | -1.157 | 0.190 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Moodiness | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.4039 | Mean Difference (Net) | 0.084 | Standard Error of the Mean | 0.10 | 2-Sided | 95 | -0.115 | 0.282 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Alertness | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.1145 | Mean Difference (Net) | -0.309 | Standard Error of the Mean | 0.19 | 2-Sided | 95 | -0.695 | 0.076 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Attention Span | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.3083 | Mean Difference (Net) | -0.127 | Standard Error of the Mean | 0.12 | 2-Sided | 95 | -0.372 | 0.119 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Motivation | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.1638 | Mean Difference (Net) | -0.183 | Standard Error of the Mean | 0.13 | 2-Sided | 95 | -0.443 | 0.0776 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Vision | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.5101 | Mean Difference (Net) | -0.078 | Standard Error of the Mean | 0.12 | 2-Sided | 95 | -0.314 | 0.157 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Energy Level | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.2285 | Mean Difference (Net) | -0.233 | Standard Error of the Mean | 0.19 | 2-Sided | 95 | -0.614 | 0.149 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Memory | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.4612 | Mean Difference (Net) | 0.118 | Standard Error of the Mean | 0.16 | 2-Sided | 95 | -0.200 | 0.436 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Walking Balance | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.5190 | Mean Difference (Net) | 0.099 | Standard Error of the Mean | 0.15 | 2-Sided | 95 | -0.205 | 0.402 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Interest in Activities | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.8479 | Mean Difference (Net) | -0.024 | Standard Error of the Mean | 0.12 | 2-Sided | 95 | -0.271 | 0.223 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Coordination | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.7808 | Mean Difference (Net) | -0.039 | Standard Error of the Mean | 0.14 | 2-Sided | 95 | -0.316 | 0.238 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Tremor | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.0083 | Mean Difference (Net) | -0.171 | Standard Error of the Mean | 0.06 | 2-Sided | 95 | -0.296 | -0.045 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Concentration | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.5068 | Mean Difference (Net) | -0.101 | Standard Error of the Mean | 0.15 | 2-Sided | 95 | -0.404 | 0.201 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Speech | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.2725 | Mean Difference (Net) | -0.068 | Standard Error of the Mean | 0.06 | 2-Sided | 95 | -0.191 | 0.055 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Forgetfulness | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.7498 | Mean Difference (Net) | 0.039 | Standard Error of the Mean | 0.12 | 2-Sided | 95 | -0.206 | 0.284 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Sleepiness | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.6554 | Mean Difference (Net) | 0.152 | Standard Error of the Mean | 0.34 | 2-Sided | 95 | -0.522 | 0.826 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Moodiness | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.4143 | Mean Difference (Net) | 0.082 | Standard Error of the Mean | 0.10 | 2-Sided | 95 | -0.116 | 0.280 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Alertness | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.7761 | Mean Difference (Net) | -0.055 | Standard Error of the Mean | 0.19 | 2-Sided | 95 | -0.441 | 0.330 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Attention Span | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.9697 | Mean Difference (Net) | 0.005 | Standard Error of the Mean | 0.12 | 2-Sided | 95 | -0.241 | 0.251 | SE of difference estimated by dividing width of 95% CI by 4. | Superiority |
| Motivation | ANOVA | Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. | 0.5118 | Mean Difference (Net) | -0.086 | Standard Error of the Mean | 0.13 | 2-Sided | 95 | -0.346 | 0.174 | Superiority | SE of difference estimated by dividing width of 95% CI by 4. |
| ANOVA |
Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. |
| 0.9705 |
| Mean Difference (Net) |
| -0.020 |
| Standard Error of the Mean |
| 0.53 |
| 2-Sided |
| 95 |
| -1.089 |
| 1.049 |
SE of difference estimated by dividing width of 95% CI by 4. |
| Superiority |
| ANOVA |
Mixed model including terms for sequence, study treatment, and period as fixed effects and subject nested within sequence as a random effect. |
| 0.9705 |
| Mean Difference (Net) |
| -0.020 |
| Standard Error of the Mean |
| 0.53 |
| 2-Sided |
| 95 |
| -1.089 |
| 1.049 |
SE of difference estimated by dividing width of 95% CI by 4. |
| Superiority |
| Subjects with SAE |
|
| Subjects Discontinued due to AE |
|