A Study to Evaluate Abuse Potential of Istradefylline

Study Overview
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Brief Summary
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This study is to evaluate the abuse potential of single-doses of istradefylline compared to placebo and phentermine in recreational stimulant users. Subjects will participate in an outpatient medical Screening visit, a 5-day Qualification (Drug Discrimination) Phase, a 6-period Treatment Phase, and an outpatient safety Follow-Up visit. Study will be approximately 25 weeks total. Within 28 days of the Screening visit, eligible subjects will be admitted to the CRU (Day -1) for the Qualification Phase. During the Qualification Phase, subjects will receive single oral doses of phentermine 60 mg and matching placebo in a randomized, double blind, crossover manner, with each drug administration separated by approximately 48 hours (Day 1 and Day 3), to ensure that they can discriminate and show positive subjective effects of the active controls. Following evaluation of eligibility, subjects may be discharged (those who fail Qualification criteria) or remain in the CRU (those who pass criteria and are eligible) and then proceed directly to the Treatment Phase. The washout interval between last drug administration in the Qualification Phase and first drug administration in the Treatment Phase will be at least 96 hours (4 days). Following confirmation of eligibility from the Qualification Phase, subjects will be randomized to one of 6 treatment sequences according to a 6x6 Williams square. Subjects will receive single oral doses of each of the 6 treatments in a randomized, double-blind, crossover manner, Istradefylline 40 mg, Istradefylline 80 mg, Istradefylline 160 mg, Phentermine 45 mg, Phentermine 90 mg, Placebo. Each drug administration will be separated by at least 21 days. Serial pharmacodynamic evaluations will be conducted up to 24 hours after each study drug administration to confirm exposure to istradefylline.

Official Title
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A Double-Blind, Randomized, Placebo- and Active-Controlled Crossover Study to Evaluate the Abuse Potential of Istradefylline in Recreational Drug Users

Conditions
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Drug Abuse

Intervention / Treatment
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* Drug: Istradefylline
* Drug: Phentermine 45 mg
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who will provide written informed consent Healthy volunteer, male and female between 18 and 55 years of age, inclusive Subjects with a body mass index (BMI) within 18.0 to 33.0 kg/m2, inclusive Subjects who are recreational drug user Exclusion Criteria: Subjects who have an alcohol or substance dependence within the 12 months Subjects who have ever been in treatment for substance use disorder Subjects who consume on average more than 5 servings of caffeinated beverages per day Subjects with a history of or presence of any clinically significant cardiovascular disease Subject with hyperthyroidism or glaucoma.

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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Istradefylline 40 mg<br>40 mg istradefylline (1 × 40 mg tablet + 3 × placebo tablets + 3 × placebo capsules) | Drug: Istradefylline<br>* Istradefylline 40, 80, 160 mg<br>* Other names: 6002;Other: Placebo<br>* Placebo<br>|
| Experimental: Istradefylline 80 mg<br>80 mg istradefylline (2 × 40 mg tablets + 2 × placebo tablets + 3 × placebo capsules) | Drug: Istradefylline<br>* Istradefylline 40, 80, 160 mg<br>* Other names: 6002;Other: Placebo<br>* Placebo<br>|
| Experimental: Istradefylline 160 mg<br>160 mg istradefylline (4 × 40 mg tablets + 3 × placebo capsules) | Drug: Istradefylline<br>* Istradefylline 40, 80, 160 mg<br>* Other names: 6002;Other: Placebo<br>* Placebo<br>|
| Active Comparator: Phentermine 45 mg<br>45 mg phentermine (4 x placebo tablets + 3 × 15 mg phentermine hydrochloride capsules) | Drug: Phentermine 45 mg<br>* Phentermine 45 or 90 mg<br>Other: Placebo<br>* Placebo<br>|
| Active Comparator: Phentermine 90 mg<br>90 mg phentermine (4 × placebo tablets + 3 × 30 mg phentermine hydrochloride capsules) | Drug: Phentermine 45 mg<br>* Phentermine 45 or 90 mg<br>Other: Placebo<br>* Placebo<br>|
| Placebo Comparator: Placebo<br>Placebo (4 × placebo tablets + 3 × placebo capsules) | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Liking VAS | To evaluate the abuse potential of istradefylline compared to phentermine and placebo. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-SSRS (Columbia Suicide Severity Rating Scale) | To evaluate the safety and tolerability of istradefylline. | 24 hours | 
| Alerness/Drowsiness, Agitation/Relaxation VAS | To evaluate the safety and tolerability of istradefylline. | 24 hours | 
| Caffine Withdrawal/Symptom Questionnaire | To evaluate the safety and tolerability of istradefylline. | 24 hours | 
| Overall Drug Liking, Take Drug Again VAS | To evaluate the safety and tolerability of istradefylline. | 24 hours | 
| Drug Similarity VAS | To evaluate the safety and tolerability of istradefylline. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recreational stimulant users, Recreational Drug Users