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| ID | Type | Description | Link |
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| 22 January 2008 |
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Compare the abuse liabilities of Staccato Alprazolam, oral immediate-release alprazolam, and Staccato Placebo.
The Phase 1 clinical study compared the abuse liabilities of Staccato Alprazolam, oral immediate-release alprazolam, and Staccato Placebo in 14 subjects with a history of sedative abuse. Subjects who met the inclusion/exclusion criteria received 2 mg of oral alprazolam and matching placebo over 2 sessions. Those who demonstrated greater liking for alprazolam versus placebo were eligible to participate in the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment sequence 1 | Other | Sequence 1: Q, 1, 2, 7, 3, 6, 4, 5; where Q=Qualifying sessions (2 mg oral alprazolam and placebo in random order), 1=placebo, 2=oral alprazolam 1 mg, 3= oral alprazolam 2 mg, 4= oral alprazolam 4 mg, 5= inhaled alprazolam 0.5 mg, 6= inhaled alprazolam 1 mg, 7= inhaled alprazolam 2 mg |
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| Treatment sequence 2 | Other | Sequence Q, 2: 2, 3, 1, 4, 7, 5, 6; where Q=Qualifying sessions (2 mg oral alprazolam and placebo in random order), 1=placebo, 2=oral alprazolam 1 mg, 3= oral alprazolam 2 mg, 4= oral alprazolam 4 mg, 5= inhaled alprazolam 0.5 mg, 6= inhaled alprazolam 1 mg, 7= inhaled alprazolam 2 mg |
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| Treatment sequence 3 | Other | Sequence 3: Q, 3, 4, 2, 5, 1, 6, 7; where Q=Qualifying sessions (2 mg oral alprazolam and placebo in random order), 1=placebo, 2=oral alprazolam 1 mg, 3= oral alprazolam 2 mg, 4= oral alprazolam 4 mg, 5= inhaled alprazolam 0.5 mg, 6= inhaled alprazolam 1 mg, 7= inhaled alprazolam 2 mg |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Inhaled placebo + oral placebo | Drug | Inhaled Staccato placebo + oral placebo |
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| Measure | Description | Time Frame |
|---|---|---|
| Response to EDQ Question Number 5, "Rate the Degree to Which You Would Like to Take the Drug Again" | The End of Day Questionnaire (EDQ) is a 7-question computerized instrument in which subjects rate the overall effect of the drug they received that day. The primary outcome measure for this trial is the categorical response to question number 5, "Rate the degree to which you would like to take the drug again", with a numerical value assigned to each of the responses allowed: 0=Not at all, 1=A little, 2=Moderately, 3=Quite a bit, 4=Very much | End of day for each of the 7 crossover treatments |
| Measure | Description | Time Frame |
|---|---|---|
| EDQ Question Number 2 "Rate Your Overall Liking of the Drug Effect" | The within patient rank (1-7) of End of Day question number 2 (of primary interest), "Rate your overall liking of the drug effect", response options range from -4 to +4:
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Roland R Griffiths, PhD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins University School of Medicine | Baltimore | Maryland | 21224 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25199955 | Result | Reissig CJ, Harrison JA, Carter LP, Griffiths RR. Inhaled vs. oral alprazolam: subjective, behavioral and cognitive effects, and modestly increased abuse potential. Psychopharmacology (Berl). 2015 Mar;232(5):871-83. doi: 10.1007/s00213-014-3721-0. Epub 2014 Sep 9. |
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IPD submitted to regulatory authorities. Others may contact Alexza Pharmaceuticals, Inc. Please send your request to ClinicalTrialsInfo@alexza.com
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Each participants was to receive all 7 interventions in a randomized order in a crossover design
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| ID | Title | Description |
|---|---|---|
| FG000 | All Subjects Entering | All subjects entering the crossover qualification period |
| Title | Milestones | Reasons Not Completed | |||||
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| Study Qualification |
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The crossover schedule is planned according to a 7-treatment, 7-period Latin Square design due to E.J. Williams (1949), which is balanced for first-order carryover effects (Fleiss, 1986). Each subject will receive all treatments in this 7-treatment, 7- period Williams Square crossover design as suggested by Chen & Tsong (2007). This Williams Square will include one replication by 1 subject of each of the 14 sequences
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In order to reduce discrimination between placebo and active Staccato Alprazolam, taste blinding will be accomplished using a rapidly dissolving, intensely flavored product (candy, strip or breath spray). The product will be administered immediately after each oral capsule dosing (at the -60-min and 0- min time points).
| Treatment sequence 4 | Other | Sequence 4: Q, 4, 5, 3, 6, 2, 7, 1; where Q=Qualifying sessions (2 mg oral alprazolam and placebo in random order), 1=placebo, 2=oral alprazolam 1 mg, 3= oral alprazolam 2 mg, 4= oral alprazolam 4 mg, 5= inhaled alprazolam 0.5 mg, 6= inhaled alprazolam 1 mg, 7= inhaled alprazolam 2 mg |
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| Treatment sequence 5 | Other | Sequence 5: Q, 5, 6, 4, 7, 3, 1, 2; where Q=Qualifying sessions (2 mg oral alprazolam and placebo in random order), 1=placebo, 2=oral alprazolam 1 mg, 3= oral alprazolam 2 mg, 4= oral alprazolam 4 mg, 5= inhaled alprazolam 0.5 mg, 6= inhaled alprazolam 1 mg, 7= inhaled alprazolam 2 mg |
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| Treatment sequence 6 | Other | Sequence 6: Q, 6, 7, 5, 1, 4, 2, 3; where Q=Qualifying sessions (2 mg oral alprazolam and placebo in random order), 1=placebo, 2=oral alprazolam 1 mg, 3= oral alprazolam 2 mg, 4= oral alprazolam 4 mg, 5= inhaled alprazolam 0.5 mg, 6= inhaled alprazolam 1 mg, 7= inhaled alprazolam 2 mg |
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| Treatment sequence 7 | Other | Sequence 7: Q, 7, 1, 6, 2, 5, 3, 4; where Q=Qualifying sessions (2 mg oral alprazolam and placebo in random order), 1=placebo, 2=oral alprazolam 1 mg, 3= oral alprazolam 2 mg, 4= oral alprazolam 4 mg, 5= inhaled alprazolam 0.5 mg, 6= inhaled alprazolam 1 mg, 7= inhaled alprazolam 2 mg |
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| Treatment sequence 8 | Other | Sequence 8: Q, 5, 4, 6, 3, 7, 2, 1; where Q=Qualifying sessions (2 mg oral alprazolam and placebo in random order), 1=placebo, 2=oral alprazolam 1 mg, 3= oral alprazolam 2 mg, 4= oral alprazolam 4 mg, 5= inhaled alprazolam 0.5 mg, 6= inhaled alprazolam 1 mg, 7= inhaled alprazolam 2 mg |
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| Treatment sequence 9 | Other | Sequence 9: Q, 6, 5, 7, 4, 1, 3, 2; where Q=Qualifying sessions (2 mg oral alprazolam and placebo in random order), 1=placebo, 2=oral alprazolam 1 mg, 3= oral alprazolam 2 mg, 4= oral alprazolam 4 mg, 5= inhaled alprazolam 0.5 mg, 6= inhaled alprazolam 1 mg, 7= inhaled alprazolam 2 mg |
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| Treatment sequence 10 | Other | Sequence 10: Q, 7, 6, 1, 5, 2, 4, 3; where Q=Qualifying sessions (2 mg oral alprazolam and placebo in random order), 1=placebo, 2=oral alprazolam 1 mg, 3= oral alprazolam 2 mg, 4= oral alprazolam 4 mg, 5= inhaled alprazolam 0.5 mg, 6= inhaled alprazolam 1 mg, 7= inhaled alprazolam 2 mg |
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| Treatment sequence 11 | Other | Sequence 11: Q, 1, 7, 2, 6, 3, 5, 4; where Q=Qualifying sessions (2 mg oral alprazolam and placebo in random order), 1=placebo, 2=oral alprazolam 1 mg, 3= oral alprazolam 2 mg, 4= oral alprazolam 4 mg, 5= inhaled alprazolam 0.5 mg, 6= inhaled alprazolam 1 mg, 7= inhaled alprazolam 2 mg |
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| Treatment sequence 12 | Other | Sequence 12: Q, 2, 1, 3, 7, 4, 6, 5; where Q=Qualifying sessions (2 mg oral alprazolam and placebo in random order), 11=placebo, 2=oral alprazolam 1 mg, 3= oral alprazolam 2 mg, 4= oral alprazolam 4 mg, 5= inhaled alprazolam 0.5 mg, 6= inhaled alprazolam 1 mg, 7= inhaled alprazolam 2 mg |
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| Treatment sequence 13 | Other | Sequence 13: Q, 3, 2, 4, 1, 5, 7, 6; where Q=Qualifying sessions (2 mg oral alprazolam and placebo in random order), 1=placebo, 2=oral alprazolam 1 mg, 3= oral alprazolam 2 mg, 4= oral alprazolam 4 mg, 5= inhaled alprazolam 0.5 mg, 6= inhaled alprazolam 1 mg, 7= inhaled alprazolam 2 mg |
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| Treatment sequence 14 | Other | Sequence 14: Q, 4, 3, 5, 2, 6, 1, 7; where Q=Qualifying sessions (2 mg oral alprazolam and placebo in random order), 11=placebo, 2=oral alprazolam 1 mg, 3= oral alprazolam 2 mg, 4= oral alprazolam 4 mg, 5= inhaled alprazolam 0.5 mg, 6= inhaled alprazolam 1 mg, 7= inhaled alprazolam 2 mg |
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| Inhaled alprazolam 0.5 mg | Drug | Inhaled Staccato alprazolam 0.5 mg + oral placebo |
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| Inhaled alprazolam 1 mg | Drug | Inhaled Staccato alprazolam 1 mg + oral placebo |
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| Inhaled alprazolam 2 mg | Drug | Inhaled Staccato alprazolam 2 mg + oral placebo |
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| Oral alprazolam 1 mg | Drug | Oral alprazolam 1 mg + Inhaled placebo |
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| Oral alprazolam 2 mg | Drug | Oral alprazolam 2 mg + Inhaled placebo |
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| Oral alprazolam 4 m | Drug | Oral alprazolam 4 mg + Inhaled placebo |
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| Oral alprazolam 2 mg qualifying session | Drug | Qualifying session (2 mg oral alprazolam) |
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| Oral placebo qualifying session | Drug | Qualifying control session (oral placebo) |
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| End of day for each of the 7 crossover treatments |
| EDQ Question Number 6 " Estimate the Amount of Money You Think the Drug You Took Today Would be Worth on the Street". | EDQ question number 6 (of primary interest)," Estimate the amount of money you think the drug you took today would be worth on the street". | End of day for each of the 7 crossover treatments |
| EDQ Question Number 1, "Rate the Overall Strength of the Drug Effect" | The within patient rank (1-7) of End of Day question number 1, "Rate the overall strength of the drug effect", response options range from 0-4: 0=No drug effect at all
| End of day for each of the 7 crossover treatments |
| EDQ Question Number 7,"What Would You be Willing to Pay for Today's Drug?" | EDQ question number 7," What would you be willing to pay for today's drug?" | End of day for each of the 7 crossover treatments |
| Maximum of DEQ Question 1 "Rate the Strength of the Drug Effect" (at the 10 Time Points, Predose Through 9 Hours) | The within patient rank (1-7) of Drug Effect Questionnaire question number 1: Rate the STRENGTH of the drug effect you are feeling RIGHT NOW; response options range for 0 to 4: "No drug effect at all"=0, "Possible mild effect, but not sure"=1, "Definite mild effect"=2, "Moderate strong drug effect"=3, "Very strong drug effect"=4 Maximum of the 10 time points (predose through 9 hours) Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | DEQ was assessed at the 10 time points (predose through 9 hours) |
| Maximum of DEQ Question 2 "Rate Your Liking of the Drug Effect" at the 10 Time Points (Predose Through 9 Hours) | The within patient rank (1-7) of maximum of the Rate your LIKING of the drug effect you are feeling RIGHT NOW; response options range from -4 to +4: "Dislike very much"=-4, "Dislike quite a bit"=-3, "Dislike somewhat"=-2, "Dislike, but not very much"=-1, "NEUTRAL OR NO EFFECT"=0, "Like, but not very much"=1, "Like somewhat"=2, "Like quite a bit"=3, "Like very much"=4 Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | DEQ was assessed at the 10 time points (predose through 9 hours) |
| Observer Rated Questionnaire 1) Maximum of Sedation/Sleepiness | The within patient rank (1-7) of Maximum of Observer Rated Questionnaire (ORQ): A trained and blinded staff member completed observer ratings as the subject completed the questionnaires and psychomotor assessment testing at each time point. The observer rated the subject on sedation/sleepiness, muscle relaxation, impaired posture, impaired speech, confusion/disorientation, stimulation/arousal and strength of drug effect on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Maximum of the 10 time points (predose through 9 hours) Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | ORQ was assessed at the 10 time points (predose through 9 hours) |
| Observer Rated Questionnaire 2) Maximum of Muscle Relaxation Locomotor | The within patient rank (1-7) of maximum of the observer rated the subject on muscle relaxation (locomotor) on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Maximum of the 10 time points (predose through 9 hours) Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | ORQ was assessed at the 10 time points (predose through 9 hours) |
| Observer Rated Questionnaire 3) Maximum of Muscle Relaxation Non-locomotor | The within patient rank (1-7) of maximum of the observer rated the subject on muscle relaxation (non-locomotor) on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | ORQ was assessed at the 10 time points (predose through 9 hours) |
| Observer Rated Questionnaire 4) Maximum of Muscle Relaxation Posture | The within patient rank (1-7) of maximum of the observer rated the subject on muscle relaxation (posture) on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | ORQ was assessed at the 10 time points (predose through 9 hours) |
| Observer Rated Questionnaire 5) Maximum of Speech | The within patient rank (1-7) of maximum of the observer rated the subject on speech on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | ORQ was assessed at the 10 time points (predose through 9 hours) |
| Observer Rated Questionnaire 6) Maximum of Confusion/Disorientation | The within patient rank (1-7) of maximum of the observer rated the subject on Confusion/Disorientation on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | ORQ was assessed at the 10 time points (predose through 9 hours) |
| Observer Rated Questionnaire 7) Maximum of Stimulation/Arousal | The within patient rank (1-7) of maximum of the observer rated the subject on Stimulation/Arousal on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | ORQ was assessed at the 10 time points (predose through 9 hours) |
| Observer Rated Questionnaire 8) Maximum of Drug Strength | The within patient rank (1-7) of maximum of the observer rated the subject on Drug Strength on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | ORQ was assessed at the 10 time points (predose through 9 hours) |
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| Main Study |
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| ID | Title | Description |
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| BG000 | Qualifying Session (Includes Crossover Group) | All subjects received Placebo and Oral alprazolam 2 mg in a randomized order to Qualify Each subject was to receive all 7 interventions (Placebo, Oral alprazolam 1, 2 & 3 mg, Inhaled alprazolam 0.5, 1, & 2 mg) in a randomized order in a crossover design |
| Units | Counts |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
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| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| 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 | ||||||||||||||||||||||||||||||||||||||
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| Primary | Response to EDQ Question Number 5, "Rate the Degree to Which You Would Like to Take the Drug Again" | The End of Day Questionnaire (EDQ) is a 7-question computerized instrument in which subjects rate the overall effect of the drug they received that day. The primary outcome measure for this trial is the categorical response to question number 5, "Rate the degree to which you would like to take the drug again", with a numerical value assigned to each of the responses allowed: 0=Not at all, 1=A little, 2=Moderately, 3=Quite a bit, 4=Very much | Efficacy (crossover) Population, n=14. LSM & SEM are based on all 14 subjects completing all 7 treatments. PROC MIXED model used assigns the same SEM to all 7 treatments. | Posted | Least Squares Mean | Standard Error | units on a scale | End of day for each of the 7 crossover treatments |
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| Secondary | EDQ Question Number 2 "Rate Your Overall Liking of the Drug Effect" | The within patient rank (1-7) of End of Day question number 2 (of primary interest), "Rate your overall liking of the drug effect", response options range from -4 to +4:
| Efficacy (crossover) Population, n=14 LS Means via SAS PROC MIXED non-parametric model (ranks within subject), treatment and period as fixed effects, ddf=72 LSM & SEM are based on the ranks of scores within each subject across all 14 subjects completing all 7 treatments. PROC MIXED model assigns the same SEM to all 7 treatments. | Posted | Least Squares Mean | Standard Error | Rank across the 7 treatments | End of day for each of the 7 crossover treatments |
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| Secondary | EDQ Question Number 6 " Estimate the Amount of Money You Think the Drug You Took Today Would be Worth on the Street". | EDQ question number 6 (of primary interest)," Estimate the amount of money you think the drug you took today would be worth on the street". | Efficacy (crossover) Population, n=14. LSM & SEM are based on all 14 subjects completing all 7 treatments. PROC MIXED model used assigns the same SEM to all 7 treatments. | Posted | Least Squares Mean | Standard Error | Dollars ($) | End of day for each of the 7 crossover treatments |
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| Secondary | EDQ Question Number 1, "Rate the Overall Strength of the Drug Effect" | The within patient rank (1-7) of End of Day question number 1, "Rate the overall strength of the drug effect", response options range from 0-4: 0=No drug effect at all
| Efficacy (crossover) Population, n=14 LS Means via SAS PROC MIXED non-parametric model (ranks within subject), treatment and period as fixed effects, ddf=72 LSM & SEM are based on the ranks of scores within each subject across all 14 subjects completing all 7 treatments. PROC MIXED model assigns the same SEM to all 7 treatments. | Posted | Least Squares Mean | Standard Error | Rank across the 7 treatments | End of day for each of the 7 crossover treatments |
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| Secondary | EDQ Question Number 7,"What Would You be Willing to Pay for Today's Drug?" | EDQ question number 7," What would you be willing to pay for today's drug?" | Efficacy (crossover) Population, n=14. LSM & SEM are based on all 14 subjects completing all 7 treatments. PROC MIXED model used assigns the same SEM to all 7 treatments. | Posted | Least Squares Mean | Standard Error | Dollars ($) | End of day for each of the 7 crossover treatments |
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| Secondary | Maximum of DEQ Question 1 "Rate the Strength of the Drug Effect" (at the 10 Time Points, Predose Through 9 Hours) | The within patient rank (1-7) of Drug Effect Questionnaire question number 1: Rate the STRENGTH of the drug effect you are feeling RIGHT NOW; response options range for 0 to 4: "No drug effect at all"=0, "Possible mild effect, but not sure"=1, "Definite mild effect"=2, "Moderate strong drug effect"=3, "Very strong drug effect"=4 Maximum of the 10 time points (predose through 9 hours) Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | Efficacy (crossover) Population, n=14 LS Means via SAS PROC MIXED non-parametric model (ranks within subject), treatment and period as fixed effects, ddf=72 LSM & SEM are based on the ranks of scores within each subject across all 14 subjects completing all 7 treatments. PROC MIXED model assigns the same SEM to all 7 treatments. | Posted | Least Squares Mean | Standard Error | Rank across the 7 treatments | DEQ was assessed at the 10 time points (predose through 9 hours) |
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| Secondary | Maximum of DEQ Question 2 "Rate Your Liking of the Drug Effect" at the 10 Time Points (Predose Through 9 Hours) | The within patient rank (1-7) of maximum of the Rate your LIKING of the drug effect you are feeling RIGHT NOW; response options range from -4 to +4: "Dislike very much"=-4, "Dislike quite a bit"=-3, "Dislike somewhat"=-2, "Dislike, but not very much"=-1, "NEUTRAL OR NO EFFECT"=0, "Like, but not very much"=1, "Like somewhat"=2, "Like quite a bit"=3, "Like very much"=4 Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | Efficacy (crossover) Population, n=14 LS Means via SAS PROC MIXED non-parametric model (ranks within subject), treatment and period as fixed effects, ddf=72 LSM & SEM are based on the ranks of scores within each subject across all 14 subjects completing all 7 treatments. PROC MIXED model assigns the same SEM to all 7 treatments. | Posted | Least Squares Mean | Standard Error | Rank across the 7 treatments | DEQ was assessed at the 10 time points (predose through 9 hours) |
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| Secondary | Observer Rated Questionnaire 1) Maximum of Sedation/Sleepiness | The within patient rank (1-7) of Maximum of Observer Rated Questionnaire (ORQ): A trained and blinded staff member completed observer ratings as the subject completed the questionnaires and psychomotor assessment testing at each time point. The observer rated the subject on sedation/sleepiness, muscle relaxation, impaired posture, impaired speech, confusion/disorientation, stimulation/arousal and strength of drug effect on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Maximum of the 10 time points (predose through 9 hours) Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | Efficacy (crossover) Population, n=14 LS Means via SAS PROC MIXED non-parametric model (ranks within subject), treatment and period as fixed effects, ddf=72 LSM & SEM are based on the ranks of scores within each subject across all 14 subjects completing all 7 treatments. PROC MIXED model assigns the same SEM to all 7 treatments. | Posted | Least Squares Mean | Standard Error | Rank across the 7 treatments | ORQ was assessed at the 10 time points (predose through 9 hours) |
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| Secondary | Observer Rated Questionnaire 2) Maximum of Muscle Relaxation Locomotor | The within patient rank (1-7) of maximum of the observer rated the subject on muscle relaxation (locomotor) on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Maximum of the 10 time points (predose through 9 hours) Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | Efficacy (crossover) Population, n=14 LS Means via SAS PROC MIXED non-parametric model (ranks within subject), treatment and period as fixed effects, ddf=72 LSM & SEM are based on the ranks of scores within each subject across all 14 subjects completing all 7 treatments. PROC MIXED model assigns the same SEM to all 7 treatments. | Posted | Least Squares Mean | Standard Error | Rank across the 7 treatments | ORQ was assessed at the 10 time points (predose through 9 hours) |
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| Secondary | Observer Rated Questionnaire 3) Maximum of Muscle Relaxation Non-locomotor | The within patient rank (1-7) of maximum of the observer rated the subject on muscle relaxation (non-locomotor) on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | Efficacy (crossover) Population, n=14 LS Means via SAS PROC MIXED non-parametric model (ranks within subject), treatment and period as fixed effects, ddf=72 LSM & SEM are based on the ranks of scores within each subject across all 14 subjects completing all 7 treatments. PROC MIXED model assigns the same SEM to all 7 treatments. | Posted | Least Squares Mean | Standard Error | units on a scale | ORQ was assessed at the 10 time points (predose through 9 hours) |
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| Secondary | Observer Rated Questionnaire 4) Maximum of Muscle Relaxation Posture | The within patient rank (1-7) of maximum of the observer rated the subject on muscle relaxation (posture) on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | Efficacy (crossover) Population, n=14 LS Means via SAS PROC MIXED non-parametric model (ranks within subject), treatment and period as fixed effects, ddf=72 LSM & SEM are based on the ranks of scores within each subject across all 14 subjects completing all 7 treatments. PROC MIXED model assigns the same SEM to all 7 treatments. | Posted | Least Squares Mean | Standard Error | Rank across the 7 treatments | ORQ was assessed at the 10 time points (predose through 9 hours) |
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| Secondary | Observer Rated Questionnaire 5) Maximum of Speech | The within patient rank (1-7) of maximum of the observer rated the subject on speech on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | Efficacy (crossover) Population, n=14 LS Means via SAS PROC MIXED non-parametric model (ranks within subject), treatment and period as fixed effects, ddf=72 LSM & SEM are based on the ranks of scores within each subject across all 14 subjects completing all 7 treatments. PROC MIXED model assigns the same SEM to all 7 treatments. | Posted | Least Squares Mean | Standard Error | Rank across the 7 treatments | ORQ was assessed at the 10 time points (predose through 9 hours) |
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| Secondary | Observer Rated Questionnaire 6) Maximum of Confusion/Disorientation | The within patient rank (1-7) of maximum of the observer rated the subject on Confusion/Disorientation on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | Efficacy (crossover) Population, n=14 LS Means via SAS PROC MIXED non-parametric model (ranks within subject), treatment and period as fixed effects, ddf=72 LSM & SEM are based on the ranks of scores within each subject across all 14 subjects completing all 7 treatments. PROC MIXED model assigns the same SEM to all 7 treatments. | Posted | Least Squares Mean | Standard Error | Rank across the 7 treatments | ORQ was assessed at the 10 time points (predose through 9 hours) |
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| Secondary | Observer Rated Questionnaire 7) Maximum of Stimulation/Arousal | The within patient rank (1-7) of maximum of the observer rated the subject on Stimulation/Arousal on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | Efficacy (crossover) Population, n=14 LS Means via SAS PROC MIXED non-parametric model (ranks within subject), treatment and period as fixed effects, ddf=72 LSM & SEM are based on the ranks of scores within each subject across all 14 subjects completing all 7 treatments. PROC MIXED model assigns the same SEM to all 7 treatments. | Posted | Least Squares Mean | Standard Error | Rank across the 7 treatments | ORQ was assessed at the 10 time points (predose through 9 hours) |
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| Secondary | Observer Rated Questionnaire 8) Maximum of Drug Strength | The within patient rank (1-7) of maximum of the observer rated the subject on Drug Strength on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | Efficacy (crossover) Population, n=14 LS Means via SAS PROC MIXED non-parametric model (ranks within subject), treatment and period as fixed effects, ddf=72 LSM & SEM are based on the ranks of scores within each subject across all 14 subjects completing all 7 treatments. PROC MIXED model assigns the same SEM to all 7 treatments. | Posted | Least Squares Mean | Standard Error | Rank across the 7 treatments | ORQ was assessed at the 10 time points (predose through 9 hours) |
|
Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse events (AEs) were assessed at 14 pre-specified time points for the 24-hour period after dosing, as well as whenever spontaneously reported by the subjects or study staff
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Inhaled Staccato Placebo +oral placebo | 0 | 15 | 0 | 15 | 0 | 15 |
| EG001 | Oral Alprazolam 1 mg | Oral alprazolam 1 mg + inhaled placebo | 0 | 15 | 0 | 15 | 0 | 15 |
| EG002 | Oral Alprazolam 2 mg | Oral alprazolam 2 mg + inhaled placebo | 0 | 14 | 0 | 14 | 0 | 14 |
| EG003 | Oral Alprazolam 4 mg | Oral alprazolam 4 mg + inhaled placebo | 0 | 15 | 0 | 15 | 1 | 15 |
| EG004 | Inhaled Alprazolam 0.5 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo | 0 | 14 | 0 | 14 | 0 | 14 |
| EG005 | Inhaled Alprazolam 1 mg | Inhaled Staccato alprazolam 1 mg + oral placebo | 0 | 15 | 0 | 15 | 0 | 15 |
| EG006 | Inhaled Alprazolam 2 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo placebo | 0 | 15 | 0 | 15 | 0 | 15 |
| EG007 | Qualifying Session 2 mg Oral | Qualifying session, 2 mg oral alprazolam | 0 | 28 | 0 | 28 | 0 | 28 |
| EG008 | Qualifying Session Oral Placebo | Qualifying session, oral placebo (alprazolam 0 mg) | 0 | 28 | 0 | 28 | 1 | 28 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sedation | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (12.0) | Systematic Assessment |
|
A limitation of the current study was the lack of assessment of drug plasma levels. The differences in abuse potential measures may be due to differences in absorption, peak drug plasma levels, or other PK parameters
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Executive VP, Research & Development, Regulatory & Quality | Alexza Pharmaceuticals, Inc | 650.944.7071 | ClinicalTrialsInfo@alexza.com |
| ID | Term |
|---|---|
| D000525 | Alprazolam |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| OG003 | Oral Alprazolam 4 mg | Oral alprazolam 4 mg + inhaled placebo |
| OG004 | Inhaled Alprazolam 0.5 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo |
| OG005 | Inhaled Alprazolam 1 mg | Inhaled Staccato alprazolam 1 mg + oral placebo |
| OG006 | Inhaled Alprazolam 2 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo placebo |
|
|
| Inhaled Alprazolam 0.5 mg |
Inhaled Staccato alprazolam 0.5 mg + oral placebo |
| OG005 | Inhaled Alprazolam 1 mg | Inhaled Staccato alprazolam 1 mg + oral placebo |
| OG006 | Inhaled Alprazolam 2 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo placebo |
|
|
| OG003 |
| Oral Alprazolam 4 mg |
Oral alprazolam 4 mg + inhaled placebo |
| OG004 | Inhaled Alprazolam 0.5 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo |
| OG005 | Inhaled Alprazolam 1 mg | Inhaled Staccato alprazolam 1 mg + oral placebo |
| OG006 | Inhaled Alprazolam 2 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo placebo |
|
|
Inhaled Staccato alprazolam 0.5 mg + oral placebo |
| OG005 | Inhaled Alprazolam 1 mg | Inhaled Staccato alprazolam 1 mg + oral placebo |
| OG006 | Inhaled Alprazolam 2 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo placebo |
|
|
Oral alprazolam 2 mg + inhaled placebo
| OG003 | Oral Alprazolam 4 mg | Oral alprazolam 4 mg + inhaled placebo |
| OG004 | Inhaled Alprazolam 0.5 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo |
| OG005 | Inhaled Alprazolam 1 mg | Inhaled Staccato alprazolam 1 mg + oral placebo |
| OG006 | Inhaled Alprazolam 2 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo placebo |
|
|
Oral alprazolam 2 mg + inhaled placebo
| OG003 | Oral Alprazolam 4 mg | Oral alprazolam 4 mg + inhaled placebo |
| OG004 | Inhaled Alprazolam 0.5 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo |
| OG005 | Inhaled Alprazolam 1 mg | Inhaled Staccato alprazolam 1 mg + oral placebo |
| OG006 | Inhaled Alprazolam 2 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo placebo |
|
|
| Oral Alprazolam 2 mg |
Oral alprazolam 2 mg + inhaled placebo |
| OG003 | Oral Alprazolam 4 mg | Oral alprazolam 4 mg + inhaled placebo |
| OG004 | Inhaled Alprazolam 0.5 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo |
| OG005 | Inhaled Alprazolam 1 mg | Inhaled Staccato alprazolam 1 mg + oral placebo |
| OG006 | Inhaled Alprazolam 2 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo placebo |
|
|
| OG003 |
| Oral Alprazolam 4 mg |
Oral alprazolam 4 mg + inhaled placebo |
| OG004 | Inhaled Alprazolam 0.5 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo |
| OG005 | Inhaled Alprazolam 1 mg | Inhaled Staccato alprazolam 1 mg + oral placebo |
| OG006 | Inhaled Alprazolam 2 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo placebo |
|
|
| Oral Alprazolam 4 mg |
Oral alprazolam 4 mg + inhaled placebo |
| OG004 | Inhaled Alprazolam 0.5 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo |
| OG005 | Inhaled Alprazolam 1 mg | Inhaled Staccato alprazolam 1 mg + oral placebo |
| OG006 | Inhaled Alprazolam 2 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo placebo |
|
|
| Oral Alprazolam 4 mg |
Oral alprazolam 4 mg + inhaled placebo |
| OG004 | Inhaled Alprazolam 0.5 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo |
| OG005 | Inhaled Alprazolam 1 mg | Inhaled Staccato alprazolam 1 mg + oral placebo |
| OG006 | Inhaled Alprazolam 2 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo placebo |
|
|
Oral alprazolam 4 mg + inhaled placebo |
| OG004 | Inhaled Alprazolam 0.5 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo |
| OG005 | Inhaled Alprazolam 1 mg | Inhaled Staccato alprazolam 1 mg + oral placebo |
| OG006 | Inhaled Alprazolam 2 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo placebo |
|
|
| Oral Alprazolam 4 mg |
Oral alprazolam 4 mg + inhaled placebo |
| OG004 | Inhaled Alprazolam 0.5 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo |
| OG005 | Inhaled Alprazolam 1 mg | Inhaled Staccato alprazolam 1 mg + oral placebo |
| OG006 | Inhaled Alprazolam 2 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo placebo |
|
|
Oral alprazolam 4 mg + inhaled placebo |
| OG004 | Inhaled Alprazolam 0.5 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo |
| OG005 | Inhaled Alprazolam 1 mg | Inhaled Staccato alprazolam 1 mg + oral placebo |
| OG006 | Inhaled Alprazolam 2 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo placebo |
|
|
Oral alprazolam 4 mg + inhaled placebo |
| OG004 | Inhaled Alprazolam 0.5 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo |
| OG005 | Inhaled Alprazolam 1 mg | Inhaled Staccato alprazolam 1 mg + oral placebo |
| OG006 | Inhaled Alprazolam 2 mg | Inhaled Staccato alprazolam 0.5 mg + oral placebo placebo |
|
|