A Study to Determine the Abuse Potential of Tozadenant Relative to D-Amphetamine and Placebo When Administered Orally in Healthy, Non-Dependent, Recreational Polydrug Users

Study Overview
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Brief Summary
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This will be a single-dose, randomized, double-blind, active- and placebo-controlled, double dummy, 6-way crossover study to determine the abuse potential of tozadenant relative to d-amphetamine and placebo, when administered orally in healthy non-dependent, recreational polydrug users with stimulant experience, under fed conditions. Each subject will participate in a medical Screening visit, a 4-day (3-night) qualification (drug discrimination) visit, six 3-day (2-night) treatment periods, and a follow-up visit.

Detailed Description
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The Qualification Phase will be conducted as a single, 4-day visit. Doses will be administered in a randomized, double-blind crossover manner following administration of a standard low-fat meal. Subjects will be dosed with 20 mg of d-amphetamine or matching placebo d-amphetamine on Day 1 and Day 2, approximately 24 hours apart. PD assessments will be conducted before dosing and at time points for up to 8 hours post dosing. Safety assessments will be conducted before dosing and for at least 24 hours following dosing. Data will be reviewed to determine subject eligibility. The last drug administration in the Qualification Phase and the first drug administration in the Treatment Phase will be separated by a washout interval of at least 7 days and not to exceed 28 days. During the Treatment Phase, there will be 6 treatment periods; subjects will receive a single oral dose of each of the following treatments with applicable matching oral placebos in a randomized, double-blind, double-dummy fashion following the administration of a standard, low-fat meal. The following treatments will be administered: Treatment A: placebo (matched to tozadenant and d-amphetamine) Treatment B: tozadenant 120 mg Treatment C: tozadenant 240 mg Treatment D: tozadenant 480 mg Treatment E: d-amphetamine 20 mg Treatment F: d-amphetamine 40 mg Drug administration will occur on Day 1 of each of the 6 treatment periods. PD and PK assessments will be collected during the 24 hours post-dose and safety assessments will be collected during the 36 hours post-dose. Subjects will be discharged on Day 2, after approximately 36 hours post-dose, or remain at the clinical research unit longer (e.g., 48 hours or until the following morning) if there are safety concerns, at the discretion of the investigator or designee. Drug administration in each treatment period will be separated by a washout interval of at least 7 days after the last dose of study drug. Subjects will return for an end-of-study safety Follow-up visit approximately 7 to 14 days after the subject's last study drug dose in the Treatment Phase or following early withdrawal.

Official Title
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A Randomized, Double-Blind, 6-Way Crossover Study to Determine the Abuse Potential of Tozadenant Relative to D-Amphetamine and Placebo When Administered Orally in Healthy, Non-Dependent, Recreational Polydrug Users With Stimulant Experience, Under Fed Conditions

Conditions
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Abuse Potential

Intervention / Treatment
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* Drug: Tozadenant
* Drug: Placebo oral tablet
* Drug: d-amphetamine
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subjects 18 to 55 years of age, inclusive. Have a body mass index (BMI) within the range of 18.0 to 30.0 kg/m2 and a minimum weight of at least 50.0 kg Current recreational polydrug users who self-report to: Have used stimulants (e.g., amphetamines, cocaine, methylphenidate) for non-therapeutic purposes (i.e., for psychoactive effects) at least 10 times in the past year and at least 1 time in the 8 weeks before Screening. Have at least 10 lifetime uses of drugs (e.g., opioids, sedatives) from at least 1 other class other than alcohol. Agree to use an approved method of contraception Be willing and able to abide by all study requirements and restrictions Additional criteria may apply Exclusion Criteria: Substance or alcohol dependence within the past 2 years, Clinically significant medical history or illness Female subjects who have a positive pregnancy test, are currently pregnant or lactating, or who are planning to become pregnant within 30 days of last study drug administration. Donation or loss of more than 500 mL whole blood within 30 days preceding the Screening visit. Additional criteria may apply.

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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Treatment A<br>Placebo oral tablet and Placebo oral capsule | Drug: Placebo oral tablet<br>* 2, 4, 6 or 8 Tozadenant matching placebo tablets<br>Drug: Placebo oral capsule<br>* 2 or 4 capsules, each containing d-amphetamine matching over-encapsulated PLACEBO 200 mg lactose tablet<br>|
| Experimental: Treatment B<br>Tozadenant 120 mg | Drug: Tozadenant<br>* 2, 4, 6 or 8 Tozadenant 60 mg tablets<br>* Other names: SYN115;Drug: Placebo oral capsule<br>* 2 or 4 capsules, each containing d-amphetamine matching over-encapsulated PLACEBO 200 mg lactose tablet<br>|
| Experimental: Treatment C<br>Tozadenant 240 mg | Drug: Tozadenant<br>* 2, 4, 6 or 8 Tozadenant 60 mg tablets<br>* Other names: SYN115;Drug: Placebo oral capsule<br>* 2 or 4 capsules, each containing d-amphetamine matching over-encapsulated PLACEBO 200 mg lactose tablet<br>|
| Experimental: Treatment D<br>Tozadenant 480 mg | Drug: Tozadenant<br>* 2, 4, 6 or 8 Tozadenant 60 mg tablets<br>* Other names: SYN115;Drug: Placebo oral capsule<br>* 2 or 4 capsules, each containing d-amphetamine matching over-encapsulated PLACEBO 200 mg lactose tablet<br>|
| Active Comparator: Treatment E<br>d-amphetamine 20 mg | Drug: Placebo oral tablet<br>* 2, 4, 6 or 8 Tozadenant matching placebo tablets<br>Drug: d-amphetamine<br>* 2 or 4 capsules, each containing 2 over-encapsulated d-amphetamine 5 mg tablets<br>|
| Active Comparator: Treatment F<br>d-amphetamine 40 mg | Drug: Placebo oral tablet<br>* 2, 4, 6 or 8 Tozadenant matching placebo tablets<br>Drug: d-amphetamine<br>* 2 or 4 capsules, each containing 2 over-encapsulated d-amphetamine 5 mg tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Liking | Drug Liking Visual Analog Scale (VAS) (at this moment), assessed on a bipolar, 0- to 100-point visual analog scale. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Balance of effects | Based on Drug Liking VAS | 24 hours | 
| Global effects | Overall Drug Liking VAS | 24 hours | 
| Positive drug effects | High VAS | 24 hours | 
| Positive drug effects | Good Drug Effects VAS | 24 hours | 
| Negative drug effects | Bad Drug Effects VAS | 24 hours | 
| Stimulant effects | Alertness/Drowsiness VAS | 24 hours | 
| Stimulant effects | Agitation/Relaxation VAS | 24 hours | 
| Other drug effects: | Hallucinations VAS | 24 hours | 
| Other drug effects: | Detached VAS | 24 hours | 
| Other drug effects: | Addiction Research Center Inventory (ARCI) | 24 hours | 
| Other drug effects: | Drug Similarity VAS | 12 hours | 
| Other drug effects: | Bowdle VAS | 24 hours | 
| Cognitive and psychomotor effects | Divided Attention Test | 24 hours | 
| Cognitive and psychomotor effects | Choice Reaction Time | 24 hours |