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

Abuse Potential Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03200080
• Other study ID #: TOZ-CL09
• Status: Terminated
• Phase: Phase 1
• Start date: September 18, 2017
• Est. completion date: November 28, 2017

Study information

• Verified date: June 2017
• Source: Biotie Therapies Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 26
• Est. completion date: November 28, 2017
• Est. primary completion date: November 28, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Abuse Potential

Intervention

Drug:
• Tozadenant
2, 4, 6 or 8 Tozadenant 60 mg tablets
• Placebo oral tablet
2, 4, 6 or 8 Tozadenant matching placebo tablets
• d-amphetamine
2 or 4 capsules, each containing 2 over-encapsulated d-amphetamine 5 mg tablets
• Placebo oral capsule
2 or 4 capsules, each containing d-amphetamine matching over-encapsulated PLACEBO 200 mg lactose tablet

Locations

Country	Name	City	State
Canada	INC Research Toronto, Inc.	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Biotie Therapies Inc.	Acorda Therapeutics

Country where clinical trial is conducted

Canada, 

Outcome

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