Study to Evaluate the Abuse Liability, Pharmacokinetics, Safety and Tolerability of an Abuse-Deterrent d-Amphetamine Sulfate Immediate Release Formulation (ADAIR)

Study Overview
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Brief Summary
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This is a randomized, double-blind, double-dummy, placebo- and active-controlled 4 period, 4 way crossover study to assess the intranasal abuse potential of manipulated ADAIR formulation in nondependent, recreational stimulant users. The study will consist of an outpatient Screening Visit, an in clinic Qualification Phase, an in-clinic Treatment Phase, and an outpatient Follow-Up visit.

Detailed Description
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VAL-104 is a phase 1, randomized, double-blind, double-dummy, placebo- and active-controlled 4 period, 4 way crossover study to assess the intranasal abuse potential of manipulated ADAIR formulation in nondependent, recreational stimulant users. The study objectives include assessing the pharmacodynamics (PD), pharmacokinetics (PK), safety and tolerability of manipulated ADAIR 30mg when compared to crushed d-amphetamine sulfate and placebo. The primary PD endpoint is mean maximum drug liking (Emax) on a bipolar 100mm visual analog scale. A total of 64 subjects demonstrating a confirmed positive response to stimulants will enter the treatment phase. Safety will be assess via adverse events, vital signs, ECGs, clinical laboratory tests and Columbia Suicide Severity Rating Scale (C-SSRS).

Official Title
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A Randomized, Double-Blind, Double-Dummy, Placebo-, Active-Controlled, 4 Period, 4 Way Crossover Study to Evaluate the Abuse Potential of Manipulated Abuse-Deterrent Dextroamphetamine Sulfate Immediate Release (ADAIR) Formulation Compared to Dextroamphetamine Sulfate Immediate Release When Administered Intranasally to Nondependent, Recreational Stimulant Users

Conditions
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Narcolepsy, ADHD

Intervention / Treatment
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* Drug: ADAIR 10 mg IR tablets
* Drug: d-amphetamine sulfate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female volunteers, 18 to 55 years of age inclusive Recreational drug abuse experience (>/= 10 times lifetime abuse of a CNS stimulant, >/= 1 abuse of CNS stimulant in the previous 3 months) Prior intranasal recreational drug abuse experience Body mass index (BMI) 18 to 33 kg/m2 inclusive Exclusion Criteria: History of any significant disease or disorder History or current diagnosis of substance dependence (excluding caffeine and nicotine) Any confirmed significant allergic reactions against any drug, or multiple allergies in the judgement of the investigator Positive for hepatitis B, hepatitis C or HIV infection Pregnant or lactating women Participation in an investigational drug or device study within the last 30 days prior to Day 1 of the study Confirmed positive drug screening Positive alcohol breath test at screening / any Day -1 Heavy smoker (> 20 cigarettes, > 8 pipefuls or > 8 cigars per day)

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral Placebo + Intranasal manipulated ADAIR<br>Oral Placebo + Intranasal manipulated ADAIR 30 mg | Drug: ADAIR 10 mg IR tablets<br>* manipulated ADAIR 3x10mg<br>* Other names: ADAIR;Drug: Placebo<br>* placebo for oral and intranasal administration<br>|
| Active Comparator: Oral Placebo + Intranasal crushed dextroamphetamine sulfate<br>Oral Placebo + Intranasal crushed dextroamphetamine sulfate IR 30 mg | Drug: d-amphetamine sulfate<br>* crushed d-amphetamine sulfate 3x10mg<br>* Other names: dextroamphetamine sulfate;Drug: Placebo<br>* placebo for oral and intranasal administration<br>|
| Experimental: Oral ADAIR + Intranasal Placebo<br>Oral ADAIR 30 mg + Intranasal Placebo | Drug: Placebo<br>* placebo for oral and intranasal administration<br>|
| Placebo Comparator: Oral Placebo + Intranasal Placebo<br>Oral Placebo + Intranasal Placebo | Drug: Placebo<br>* placebo for oral and intranasal administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Liking Emax Visual Analog Scale (VAS) | Peak effect for drug liking based on bipolar VAS from 0-100 scale | Up to 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Take Drug Again Emax VAS | Peak effect for take drug again based on bipolar VAS from 0-100 scale | Up to 24 hours post dose | 
| Overall Drug Liking Emax VAS | Peak effect for overall drug liking based on bipolar VAS from 0-100 scale | Up to 24 hours post dose | 
| Plasma concentrations (PK parameters) | plasma concentrations of ADAIR and dextroamphetamine sulfate | Up to 36 hours post dose | 
| Safety (adverse events) | Incidence of adverse events | Day 1 to Day 18 |