Clinical trial NCT03152123: Determination the Abuse Potential of Pitolisant in Healthy, Non-Dependent Recreational Stimulant Users
Official title: A Randomized, Double-Blind, Active- and Placebo-Controlled, Single-Dummy, 4-Way Crossover Study to Determine the Abuse Potential of Pitolisant Compared to Phentermine and Placebo, in Healthy, Non-Dependent Recreational Stimulant Users
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Drug Abuse
Lead sponsor: Bioprojet
Sponsor class: OTHER
First posted: 2017-05-12
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the abuse potential of single doses of pitolisant relative to phentermine HCl and placebo, when administered to healthy, non-dependent, recreational stimulant users.


Eligibility criteria: Inclusion Criteria:

* Healthy male or female subjects 18 to 55 years of age, inclusive.
* Must understand and provide written informed consent, prior to the initiation of any protocol-specific procedures.
* Current stimulant users who have used stimulants for recreational (non-therapeutic) purposes, (ie, for psychoactive effects) at least 10 times in the past year and used stimulants at least 1 time in the 8 weeks before Screening.
* Female subjects of childbearing potential with male sexual partners must be using and willing to continue using medically acceptable contraception for at least 1 month prior to Screening (at least 3 months for oral and transdermal contraceptives) and for at least 1 month after last study drug administration.
* Male subjects with female sexual partners of childbearing potential must be using and willing to continue using medically acceptable contraception from Screening and for at least 1 month after the last study drug administration.
* Able to speak, read, and understand English sufficiently to allow completion of all study assessments.

Exclusion Criteria:

* Substance or alcohol dependence (excluding nicotine and caffeine) within the past 2 years, as defined by the Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition - Text Revision (DSM IV-TR), and/or has ever participated or plans to participate in a substance or alcohol rehabilitation program to treat their substance or alcohol dependence.
* History or presence of clinically significant abnormality as assessed by physical examination, medical history, vital signs, or laboratory values, which in the opinion of the investigator would jeopardize the safety of the subject or the validity of the study results.
* History or presence of motor tics, Tourette's syndrome, or significant anxiety, tension, or agitation.
* Presence of thyrotoxicosis, advanced arteriosclerosis, glaucoma, pheochromocytoma, acid related gastric disorders, or peripheral vasculopathy (including Raynaud's phenomenon).
* History or presence of cardiovascular disorder (eg, moderate to severe hypertension, angina, arterial occlusive disease, heart failure, hemodynamically significant congenital heart disease, cardiomyopathies, myocardial infarction, potentially life-threatening arrhythmias and channelopathies \[disorders caused by the dysfunction of ion channels\]), or other serious cardia problems.
* History or presence of CNS abnormalities (eg, cerebral aneurysm, vascular abnormalities, stroke), seizures, convulsions, or epilepsy.
* History or presence of clinically significant abnormality as assessed by ECG, long QTc syndrome (eg, syncope or arrhythmia), or presence QTcF interval \>450 msec.
* Evidence of clinically significant hepatic or renal impairment including alanine aminotransferase or aspartate aminotransferase \> 1.5 × the upper limit of normal (ULN) or bilirubin \> 1 × ULN.
* Positive for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
* History of allergy or hypersensitivity to pitolisant, phentermine HCl, or related drugs (eg, sympathomimetic amines) or known excipients of any of the drug products in this study (eg, lactose).
* History of severe allergic reaction (including anaphylaxis) to any substance or previous status asthmaticus.
* Subjects with any history of suicidal ideation or suicidal behavior, as assessed by the C SSRS (baseline version).
* Treatment with an investigational drug within 5 times the elimination half-life, if known (eg, a marketed product), or within 30 days (if the elimination half-life is unknown) prior to the first study drug administration or is concurrently enrolled in any research, judged not to be scientifically or medically compatible with this study.

Primary outcomes:
measure: Maximum effect (Emax) on Drug Liking visual analog scale (VAS)
timeFrame: Within 24 hours post-dose
Secondary outcomes:
measure: Drug Liking VAS (minimum effect [Emin] and time-averaged area under the effect curve to 24 hours after study drug administration [TA_AUE])
timeFrame: Within 24 hours post-dose
measure: Overall Drug Liking VAS (Emax/Emin)
timeFrame: Within 24 hours post-dose
measure: Take Drug Again VAS (Emax)
timeFrame: Within 24 hours post-dose
measure: Good Effects VAS (Emax and TA_AUE)
timeFrame: Within 24 hours post-dose
measure: Bad Effects VAS (Emax and TA_AUE)
timeFrame: Within 24 hours post-dose
measure: ARCI-A scale (Emax and TA_AUE)
timeFrame: Within 24 hours post-dose
measure: ARCI-BG scale (Emax and TA_AUE)
timeFrame: Within 24 hours post-dose
measure: Agitation/Relaxation VAS (Emax and TA_AUE)
timeFrame: Within 24 hours post-dose
measure: Drug Similarity VAS (score at 24 hours after study drug administration)
timeFrame: Within 24 hours post-dose
measure: Safety and tolerability of Pitolisan HCl as assessed by AEs
timeFrame: Up to 6 weeks
measure: Safety and tolerability of Pitolisan HCl by laboratory assessments
timeFrame: Up to 6 weeks
measure: Safety and tolerability of Pitolisan HCl as assessed by 12-lead ECGs
timeFrame: Up to 6 weeks
measure: Safety and tolerability of Pitolisan HCl as assessed by vital signs
timeFrame: Up to 6 weeks
measure: Safety and tolerability of Pitolisan HCl as assessed by physical examination
timeFrame: Up to 6 weeks
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: INC Research
state: Ontario
Study officials:
affiliation: Syneos Health
name: Michael B. McDonnell, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Setnik B, McDonnell M, Mills C, Scart-Gres C, Robert P, Dayno JM, Schwartz JC. Evaluation of the abuse potential of pitolisant, a selective H3-receptor antagonist/inverse agonist, for the treatment of adult patients with narcolepsy with or without cataplexy. Sleep. 2020 Apr 15;43(4):zsz252. doi: 10.1093/sleep/zsz252.