A Study to Evaluate Abuse Potential of Istradefylline

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

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.

Study Overview

• Status: Completed
• Conditions: Drug Abuse
• Intervention / Treatment: Other: Placebo; Drug: Istradefylline; Drug: Phentermine 45 mg

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Pharmaceutical Research Associates, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kyowa Hakko Kirin Pharma, Inc.
• Collaborators: Kyowa Kirin Co., Ltd.
• Investigators: Study Chair: Kyowa Hakko Kirin Pharma, Inc., Kyowa Hakko Kirin Pharma, Inc.

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: November 13, 2015
• First Submitted That Met QC Criteria: November 18, 2015
• First Posted (Estimate): November 20, 2015

Study Record Updates

• Last Update Posted (Estimate): August 18, 2016
• Last Update Submitted That Met QC Criteria: August 17, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Recreational stimulant users; Recreational Drug Users
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Purinergic Antagonists; Purinergic Agents; Appetite Depressants; Anti-Obesity Agents; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Sympathomimetics; Adenosine A2 Receptor Antagonists; Phentermine; Istradefylline
• Other Study ID Numbers: 6002-017