Staccato Alprazolam Abuse Liability

Study Overview
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Brief Summary
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Compare the abuse liabilities of Staccato Alprazolam, oral immediate-release alprazolam, and Staccato Placebo.

Detailed Description
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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.

Official Title
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Abuse Liability Study of Staccato® Alprazolam for Inhalation in Subjects With Histories of Sedative Abuse

Conditions
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Abuse Liability of Staccato Alprazolam

Intervention / Treatment
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* Drug: Inhaled placebo + oral placebo
* Drug: Inhaled alprazolam 0.5 mg
* Drug: Inhaled alprazolam 1 mg
* Drug: Inhaled alprazolam 2 mg
* Drug: Oral alprazolam 1 mg
* Drug: Oral alprazolam 2 mg
* Drug: Oral alprazolam 4 m
* Drug: Oral alprazolam 2 mg qualifying session
* Drug: Oral placebo qualifying session


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects between the ages of 18 to 55 years, inclusive, who have a history of substance abuse or dependence on barbiturates and/or benzodiazepine receptor agonists for their intoxicating effects Exclusion Criteria: Subjects with a significant current psychiatric illness or taking any psychotropic prescription medications for therapeutic uses.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment sequence 1<br>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 | Drug: Inhaled placebo + oral placebo<br>* Inhaled Staccato placebo + oral placebo<br>Drug: Inhaled alprazolam 0.5 mg<br>* Inhaled Staccato alprazolam 0.5 mg + oral placebo<br>Drug: Inhaled alprazolam 1 mg<br>* Inhaled Staccato alprazolam 1 mg + oral placebo<br>Drug: Inhaled alprazolam 2 mg<br>* Inhaled Staccato alprazolam 2 mg + oral placebo<br>Drug: Oral alprazolam 1 mg<br>* Oral alprazolam 1 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg<br>* Oral alprazolam 2 mg + Inhaled placebo<br>Drug: Oral alprazolam 4 m<br>* Oral alprazolam 4 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg qualifying session<br>* Qualifying session (2 mg oral alprazolam)<br>Drug: Oral placebo qualifying session<br>* Qualifying control session (oral placebo)<br>|
| Other: Treatment sequence 2<br>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 | Drug: Inhaled placebo + oral placebo<br>* Inhaled Staccato placebo + oral placebo<br>Drug: Inhaled alprazolam 0.5 mg<br>* Inhaled Staccato alprazolam 0.5 mg + oral placebo<br>Drug: Inhaled alprazolam 1 mg<br>* Inhaled Staccato alprazolam 1 mg + oral placebo<br>Drug: Inhaled alprazolam 2 mg<br>* Inhaled Staccato alprazolam 2 mg + oral placebo<br>Drug: Oral alprazolam 1 mg<br>* Oral alprazolam 1 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg<br>* Oral alprazolam 2 mg + Inhaled placebo<br>Drug: Oral alprazolam 4 m<br>* Oral alprazolam 4 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg qualifying session<br>* Qualifying session (2 mg oral alprazolam)<br>Drug: Oral placebo qualifying session<br>* Qualifying control session (oral placebo)<br>|
| Other: Treatment sequence 3<br>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 | Drug: Inhaled placebo + oral placebo<br>* Inhaled Staccato placebo + oral placebo<br>Drug: Inhaled alprazolam 0.5 mg<br>* Inhaled Staccato alprazolam 0.5 mg + oral placebo<br>Drug: Inhaled alprazolam 1 mg<br>* Inhaled Staccato alprazolam 1 mg + oral placebo<br>Drug: Inhaled alprazolam 2 mg<br>* Inhaled Staccato alprazolam 2 mg + oral placebo<br>Drug: Oral alprazolam 1 mg<br>* Oral alprazolam 1 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg<br>* Oral alprazolam 2 mg + Inhaled placebo<br>Drug: Oral alprazolam 4 m<br>* Oral alprazolam 4 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg qualifying session<br>* Qualifying session (2 mg oral alprazolam)<br>Drug: Oral placebo qualifying session<br>* Qualifying control session (oral placebo)<br>|
| Other: Treatment sequence 4<br>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 | Drug: Inhaled placebo + oral placebo<br>* Inhaled Staccato placebo + oral placebo<br>Drug: Inhaled alprazolam 0.5 mg<br>* Inhaled Staccato alprazolam 0.5 mg + oral placebo<br>Drug: Inhaled alprazolam 1 mg<br>* Inhaled Staccato alprazolam 1 mg + oral placebo<br>Drug: Inhaled alprazolam 2 mg<br>* Inhaled Staccato alprazolam 2 mg + oral placebo<br>Drug: Oral alprazolam 1 mg<br>* Oral alprazolam 1 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg<br>* Oral alprazolam 2 mg + Inhaled placebo<br>Drug: Oral alprazolam 4 m<br>* Oral alprazolam 4 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg qualifying session<br>* Qualifying session (2 mg oral alprazolam)<br>Drug: Oral placebo qualifying session<br>* Qualifying control session (oral placebo)<br>|
| Other: Treatment sequence 5<br>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 | Drug: Inhaled placebo + oral placebo<br>* Inhaled Staccato placebo + oral placebo<br>Drug: Inhaled alprazolam 0.5 mg<br>* Inhaled Staccato alprazolam 0.5 mg + oral placebo<br>Drug: Inhaled alprazolam 1 mg<br>* Inhaled Staccato alprazolam 1 mg + oral placebo<br>Drug: Inhaled alprazolam 2 mg<br>* Inhaled Staccato alprazolam 2 mg + oral placebo<br>Drug: Oral alprazolam 1 mg<br>* Oral alprazolam 1 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg<br>* Oral alprazolam 2 mg + Inhaled placebo<br>Drug: Oral alprazolam 4 m<br>* Oral alprazolam 4 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg qualifying session<br>* Qualifying session (2 mg oral alprazolam)<br>Drug: Oral placebo qualifying session<br>* Qualifying control session (oral placebo)<br>|
| Other: Treatment sequence 6<br>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 | Drug: Inhaled placebo + oral placebo<br>* Inhaled Staccato placebo + oral placebo<br>Drug: Inhaled alprazolam 0.5 mg<br>* Inhaled Staccato alprazolam 0.5 mg + oral placebo<br>Drug: Inhaled alprazolam 1 mg<br>* Inhaled Staccato alprazolam 1 mg + oral placebo<br>Drug: Inhaled alprazolam 2 mg<br>* Inhaled Staccato alprazolam 2 mg + oral placebo<br>Drug: Oral alprazolam 1 mg<br>* Oral alprazolam 1 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg<br>* Oral alprazolam 2 mg + Inhaled placebo<br>Drug: Oral alprazolam 4 m<br>* Oral alprazolam 4 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg qualifying session<br>* Qualifying session (2 mg oral alprazolam)<br>Drug: Oral placebo qualifying session<br>* Qualifying control session (oral placebo)<br>|
| Other: Treatment sequence 7<br>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 | Drug: Inhaled placebo + oral placebo<br>* Inhaled Staccato placebo + oral placebo<br>Drug: Inhaled alprazolam 0.5 mg<br>* Inhaled Staccato alprazolam 0.5 mg + oral placebo<br>Drug: Inhaled alprazolam 1 mg<br>* Inhaled Staccato alprazolam 1 mg + oral placebo<br>Drug: Inhaled alprazolam 2 mg<br>* Inhaled Staccato alprazolam 2 mg + oral placebo<br>Drug: Oral alprazolam 1 mg<br>* Oral alprazolam 1 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg<br>* Oral alprazolam 2 mg + Inhaled placebo<br>Drug: Oral alprazolam 4 m<br>* Oral alprazolam 4 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg qualifying session<br>* Qualifying session (2 mg oral alprazolam)<br>Drug: Oral placebo qualifying session<br>* Qualifying control session (oral placebo)<br>|
| Other: Treatment sequence 8<br>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 | Drug: Inhaled placebo + oral placebo<br>* Inhaled Staccato placebo + oral placebo<br>Drug: Inhaled alprazolam 0.5 mg<br>* Inhaled Staccato alprazolam 0.5 mg + oral placebo<br>Drug: Inhaled alprazolam 1 mg<br>* Inhaled Staccato alprazolam 1 mg + oral placebo<br>Drug: Inhaled alprazolam 2 mg<br>* Inhaled Staccato alprazolam 2 mg + oral placebo<br>Drug: Oral alprazolam 1 mg<br>* Oral alprazolam 1 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg<br>* Oral alprazolam 2 mg + Inhaled placebo<br>Drug: Oral alprazolam 4 m<br>* Oral alprazolam 4 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg qualifying session<br>* Qualifying session (2 mg oral alprazolam)<br>Drug: Oral placebo qualifying session<br>* Qualifying control session (oral placebo)<br>|
| Other: Treatment sequence 9<br>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 | Drug: Inhaled placebo + oral placebo<br>* Inhaled Staccato placebo + oral placebo<br>Drug: Inhaled alprazolam 0.5 mg<br>* Inhaled Staccato alprazolam 0.5 mg + oral placebo<br>Drug: Inhaled alprazolam 1 mg<br>* Inhaled Staccato alprazolam 1 mg + oral placebo<br>Drug: Inhaled alprazolam 2 mg<br>* Inhaled Staccato alprazolam 2 mg + oral placebo<br>Drug: Oral alprazolam 1 mg<br>* Oral alprazolam 1 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg<br>* Oral alprazolam 2 mg + Inhaled placebo<br>Drug: Oral alprazolam 4 m<br>* Oral alprazolam 4 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg qualifying session<br>* Qualifying session (2 mg oral alprazolam)<br>Drug: Oral placebo qualifying session<br>* Qualifying control session (oral placebo)<br>|
| Other: Treatment sequence 10<br>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 | Drug: Inhaled placebo + oral placebo<br>* Inhaled Staccato placebo + oral placebo<br>Drug: Inhaled alprazolam 0.5 mg<br>* Inhaled Staccato alprazolam 0.5 mg + oral placebo<br>Drug: Inhaled alprazolam 1 mg<br>* Inhaled Staccato alprazolam 1 mg + oral placebo<br>Drug: Inhaled alprazolam 2 mg<br>* Inhaled Staccato alprazolam 2 mg + oral placebo<br>Drug: Oral alprazolam 1 mg<br>* Oral alprazolam 1 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg<br>* Oral alprazolam 2 mg + Inhaled placebo<br>Drug: Oral alprazolam 4 m<br>* Oral alprazolam 4 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg qualifying session<br>* Qualifying session (2 mg oral alprazolam)<br>Drug: Oral placebo qualifying session<br>* Qualifying control session (oral placebo)<br>|
| Other: Treatment sequence 11<br>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 | Drug: Inhaled placebo + oral placebo<br>* Inhaled Staccato placebo + oral placebo<br>Drug: Inhaled alprazolam 0.5 mg<br>* Inhaled Staccato alprazolam 0.5 mg + oral placebo<br>Drug: Inhaled alprazolam 1 mg<br>* Inhaled Staccato alprazolam 1 mg + oral placebo<br>Drug: Inhaled alprazolam 2 mg<br>* Inhaled Staccato alprazolam 2 mg + oral placebo<br>Drug: Oral alprazolam 1 mg<br>* Oral alprazolam 1 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg<br>* Oral alprazolam 2 mg + Inhaled placebo<br>Drug: Oral alprazolam 4 m<br>* Oral alprazolam 4 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg qualifying session<br>* Qualifying session (2 mg oral alprazolam)<br>Drug: Oral placebo qualifying session<br>* Qualifying control session (oral placebo)<br>|
| Other: Treatment sequence 12<br>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 | Drug: Inhaled placebo + oral placebo<br>* Inhaled Staccato placebo + oral placebo<br>Drug: Inhaled alprazolam 0.5 mg<br>* Inhaled Staccato alprazolam 0.5 mg + oral placebo<br>Drug: Inhaled alprazolam 1 mg<br>* Inhaled Staccato alprazolam 1 mg + oral placebo<br>Drug: Inhaled alprazolam 2 mg<br>* Inhaled Staccato alprazolam 2 mg + oral placebo<br>Drug: Oral alprazolam 1 mg<br>* Oral alprazolam 1 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg<br>* Oral alprazolam 2 mg + Inhaled placebo<br>Drug: Oral alprazolam 4 m<br>* Oral alprazolam 4 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg qualifying session<br>* Qualifying session (2 mg oral alprazolam)<br>Drug: Oral placebo qualifying session<br>* Qualifying control session (oral placebo)<br>|
| Other: Treatment sequence 13<br>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 | Drug: Inhaled placebo + oral placebo<br>* Inhaled Staccato placebo + oral placebo<br>Drug: Inhaled alprazolam 0.5 mg<br>* Inhaled Staccato alprazolam 0.5 mg + oral placebo<br>Drug: Inhaled alprazolam 1 mg<br>* Inhaled Staccato alprazolam 1 mg + oral placebo<br>Drug: Inhaled alprazolam 2 mg<br>* Inhaled Staccato alprazolam 2 mg + oral placebo<br>Drug: Oral alprazolam 1 mg<br>* Oral alprazolam 1 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg<br>* Oral alprazolam 2 mg + Inhaled placebo<br>Drug: Oral alprazolam 4 m<br>* Oral alprazolam 4 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg qualifying session<br>* Qualifying session (2 mg oral alprazolam)<br>Drug: Oral placebo qualifying session<br>* Qualifying control session (oral placebo)<br>|
| Other: Treatment sequence 14<br>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 | Drug: Inhaled placebo + oral placebo<br>* Inhaled Staccato placebo + oral placebo<br>Drug: Inhaled alprazolam 0.5 mg<br>* Inhaled Staccato alprazolam 0.5 mg + oral placebo<br>Drug: Inhaled alprazolam 1 mg<br>* Inhaled Staccato alprazolam 1 mg + oral placebo<br>Drug: Inhaled alprazolam 2 mg<br>* Inhaled Staccato alprazolam 2 mg + oral placebo<br>Drug: Oral alprazolam 1 mg<br>* Oral alprazolam 1 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg<br>* Oral alprazolam 2 mg + Inhaled placebo<br>Drug: Oral alprazolam 4 m<br>* Oral alprazolam 4 mg + Inhaled placebo<br>Drug: Oral alprazolam 2 mg qualifying session<br>* Qualifying session (2 mg oral alprazolam)<br>Drug: Oral placebo qualifying session<br>* Qualifying control session (oral placebo)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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: 4=Dislike very much 3=Dislike quite a bit 2=Dislike somewhat 1=Dislike, but not very much 0=NEUTRAL OR NO EFFECT 1=Like, but not very much 2=Like somewhat 3=Like quite a bit 4=Like very much Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | 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 Possible mild effect, but not sure Definite mild effect Moderate strong drug effect Very strong drug effect Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect | 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) |