Determination the Abuse Potential of Pitolisant in Healthy, Non-Dependent Recreational Stimulant Users

NCT03152123 | Completed Phase 1

• 1 other identifier: P16-02 / BF2.649
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy; Drug Abuse

Outcome Measures

Primary Outcomes (1)

• Maximum effect (Emax) on Drug Liking visual analog scale (VAS)

  Drug liking VAS is one of the measures of balance of effects that assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar visual analogue scale (VAS) anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the left with "strong disliking" (score of 0 mm) and on the right with "strong liking" (score of 100 mm).

  Within 24 hours post-dose

Secondary Outcomes (14)

• Drug Liking VAS (minimum effect [Emin] and time-averaged area under the effect curve to 24 hours after study drug administration [TA_AUE])

  Within 24 hours post-dose

• Overall Drug Liking VAS (Emax/Emin)

  Within 24 hours post-dose

• Take Drug Again VAS (Emax)

  Within 24 hours post-dose

• Good Effects VAS (Emax and TA_AUE)

  Within 24 hours post-dose

• Bad Effects VAS (Emax and TA_AUE)

  Within 24 hours post-dose

Study Arms (4)

Pitolisant HCl, 40 mg

EXPERIMENTAL

Pitolisant HCl, 40 mg administered as 2 capsules, each containing 1 × 20 mg pitolisant HCl tablet (over-encapsulated), and 2 capsules, each containing 1 × 100 mg lactose tablet (over-encapsulated)

Drug: Pitolisant

Pitolisant HCl, 240 mg

EXPERIMENTAL

Pitolisant HCl, 240 mg administered as 4 capsules, each containing 60 mg pitolisant HCl (3 x 20 mg pitolisant HCl tablets, encapsulated in 1 capsule)

Drug: Pitolisant

Phentermine HCl, 60 mg

ACTIVE COMPARATOR

Phentermine HCl, 60 mg administered as 2 capsules, each containing 1 × 30 mg phentermine HCl capsule (over- encapsulated), and 2 capsules, each containing 1 × 100 mg lactose tablet (over-encapsulated)

Drug: Phentermine

Placebo

PLACEBO COMPARATOR

Placebo administered as 4 capsules, each containing 1 × 100 mg lactose tablet (over-encapsulated)

Drug: Placebos

Interventions

Pitolisant DRUG

Pitolisant 40 mg or 240 mg (tablets over-capsuled)

Also known as: BF2.649

Pitolisant HCl, 240 mg; Pitolisant HCl, 40 mg

Placebos DRUG

tablets over-capsuled

Placebo

Phentermine DRUG

Phentermine 60 mg (capsule over-capsuled)

Phentermine HCl, 60 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bioprojet: lead

Study Sites (1)

INC Research

Toronto, Ontario, M5V 2T3, Canada

Location

Related Publications (1)

• 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.

  PMID: 31626696 DERIVED

MeSH Terms

Conditions

Substance-Related Disorders

Interventions

pitolisant; Phentermine

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Michael B. McDonnell, MD

  Syneos Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2017
• First Posted: May 12, 2017
• Study Start: March 15, 2017
• Primary Completion: October 23, 2017
• Study Completion: October 23, 2017
• Last Updated: November 13, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)