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

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

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.

Study Overview

• Status: Terminated
• Conditions: Abuse Potential
• Intervention / Treatment: Drug: Placebo oral tablet; Drug: Placebo oral capsule; Drug: Tozadenant; Drug: d-amphetamine

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5V 2T3
      • INC Research Toronto, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Biotie Therapies Inc.
• Collaborators: Acorda Therapeutics
• Investigators: Principal Investigator: Michael McDonnell, MD, INC Research Toronto

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2017
• Primary Completion (Actual): November 28, 2017
• Study Completion (Actual): November 28, 2017

Study Registration Dates

• First Submitted: March 14, 2017
• First Submitted That Met QC Criteria: June 23, 2017
• First Posted (Actual): June 27, 2017

Study Record Updates

• Last Update Posted (Actual): August 13, 2018
• Last Update Submitted That Met QC Criteria: August 9, 2018
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Sympathomimetics; Adrenergic Uptake Inhibitors; Amphetamine; Dextroamphetamine
• Other Study ID Numbers: TOZ-CL09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No