Abuse PotentialPhase 1NCT03200080
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 Phase 1 study testing Tozadenant and d-amphetamine in people with Abuse Potential, run by Biotie Therapies Inc. at 1 site in Canada.
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… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Abuse Potential
- What is being tested?
- Tozadenant and d-amphetamine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteCanada
- Study dates
- 18 Sep 2017to 28 Nov 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Abuse Potential
- Being tested
- Tozadenant, Placebo oral tablet, d-amphetamine, Placebo oral capsule
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TozadenantDrug
Also called SYN115
2, 4, 6 or 8 Tozadenant 60 mg tablets
Placebo oral tabletDrug
2, 4, 6 or 8 Tozadenant matching placebo tablets
d-amphetamineDrug
2 or 4 capsules, each containing 2 over-encapsulated d-amphetamine 5 mg tablets
Placebo oral capsuleDrug
2 or 4 capsules, each containing d-amphetamine matching over-encapsulated PLACEBO 200 mg lactose tablet
| Study group | Role | What they receive |
|---|---|---|
| Treatment A | Placebo comparator | Placebo oral tablet and Placebo oral capsule Receives: Drug: Placebo oral tablet; Drug: Placebo oral capsule |
| Treatment B | Experimental | Tozadenant 120 mg Receives: Drug: Tozadenant; Drug: Placebo oral capsule |
| Treatment C | Experimental | Tozadenant 240 mg Receives: Drug: Tozadenant; Drug: Placebo oral capsule |
| Treatment D | Experimental | Tozadenant 480 mg Receives: Drug: Tozadenant; Drug: Placebo oral capsule |
| Treatment E | Active comparator | d-amphetamine 20 mg Receives: Drug: Placebo oral tablet; Drug: d-amphetamine |
| Treatment F | Active comparator | d-amphetamine 40 mg Receives: Drug: Placebo oral tablet; Drug: d-amphetamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Drug Liking
Drug Liking Visual Analog Scale (VAS) ("at this moment"), assessed on a bipolar, 0- to 100-point visual analog scale.
Measured: 24 hours
Secondary outcomes (14)
Balance of effects
Based on Drug Liking VAS
Measured: 24 hours
Global effects
Overall Drug Liking VAS
Measured: 24 hours
Positive drug effects
High VAS
Measured: 24 hours
Positive drug effects
Good Drug Effects VAS
Measured: 24 hours
Negative drug effects
Bad Drug Effects VAS
Measured: 24 hours
Stimulant effects
Alertness/Drowsiness VAS
Measured: 24 hours
Stimulant effects
Agitation/Relaxation VAS
Measured: 24 hours
Other drug effects:
Hallucinations VAS
Measured: 24 hours
Other drug effects:
Detached VAS
Measured: 24 hours
Other drug effects:
Addiction Research Center Inventory (ARCI)
Measured: 24 hours
Other drug effects:
Drug Similarity VAS
Measured: 12 hours
Other drug effects:
Bowdle VAS
Measured: 24 hours
Cognitive and psychomotor effects
Divided Attention Test
Measured: 24 hours
Cognitive and psychomotor effects
Choice Reaction Time
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2017
- Study start18 Sep 2017
- Primary completion28 Nov 2017
- Study completion28 Nov 2017
Why it stopped: New Safety Information
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Abuse PotentialStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biotie Therapies Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Acorda Therapeutics
- Responsible party
- Sponsor
- Investigators
- Michael McDonnell, MD, Principal investigator, INC Research Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03200080
- Sponsor's protocol ID
- TOZ-CL09
- Status last verified
- Jun 2017
- First submitted
- 14 Mar 2017
- Last updated
- 13 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03200080
- Acronym / sponsor ID
- TOZ-CL09
- Conditions
- Abuse Potential
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: New Safety Information
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Biotie Therapies Inc.Industry (pharma, biotech, devices)
- Collaborators
- Acorda Therapeutics
- Study start
- 18 Sep 2017 (actual)
- Primary completion
- 28 Nov 2017 (actual)
- Study completion
- 28 Nov 2017 (actual)
- First posted
- 27 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Treatment A | Placebo comparator | Drug: Placebo oral tablet, Drug: Placebo oral capsulePlacebo oral tablet and Placebo oral capsule |
| Treatment B | Experimental | Drug: Tozadenant, Drug: Placebo oral capsuleTozadenant 120 mg |
| Treatment C | Experimental | Drug: Tozadenant, Drug: Placebo oral capsuleTozadenant 240 mg |
| Treatment D | Experimental | Drug: Tozadenant, Drug: Placebo oral capsuleTozadenant 480 mg |
| Treatment E | Active comparator | Drug: Placebo oral tablet, Drug: d-amphetamined-amphetamine 20 mg |
| Treatment F | Active comparator | Drug: Placebo oral tablet, Drug: d-amphetamined-amphetamine 40 mg |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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:
- Agree to use an approved method of contraception
- Be willing and able to abide by all study requirements and restrictions
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TozadenantAlso: SYN1152, 4, 6 or 8 Tozadenant 60 mg tablets | Drug | Treatment B, Treatment C, Treatment D |
| Placebo oral tablet2, 4, 6 or 8 Tozadenant matching placebo tablets | Drug | Treatment A, Treatment E, Treatment F |
| d-amphetamine2 or 4 capsules, each containing 2 over-encapsulated d-amphetamine 5 mg tablets | Drug | Treatment E, Treatment F |
| Placebo oral capsule2 or 4 capsules, each containing d-amphetamine matching over-encapsulated PLACEBO 200 mg lactose tablet | Drug | Treatment A, Treatment B, Treatment C, Treatment D |
Primary outcome
Drug Liking
Time frame: 24 hours
Drug Liking Visual Analog Scale (VAS) ("at this moment"), assessed on a bipolar, 0- to 100-point visual analog scale.
14 secondary outcomes
Balance of effects
Time frame: 24 hours
Global effects
Time frame: 24 hours
Positive drug effects
Time frame: 24 hours
Positive drug effects
Time frame: 24 hours
Negative drug effects
Time frame: 24 hours
Stimulant effects
Time frame: 24 hours
Stimulant effects
Time frame: 24 hours
Other drug effects:
Time frame: 24 hours
Other drug effects:
Time frame: 24 hours
Other drug effects:
Time frame: 24 hours
Other drug effects:
Time frame: 12 hours
Other drug effects:
Time frame: 24 hours
Cognitive and psychomotor effects
Time frame: 24 hours
Cognitive and psychomotor effects
Time frame: 24 hours
Results and safety
The study was stopped early (reason given: New Safety Information). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2018.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael McDonnell, MD principal investigator
INC Research Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tozadenant and d-amphetamine in people with Abuse Potential, run by Biotie Therapies Inc. at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: New Safety Information). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Drug Liking (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2018.