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

Bioprojet

Status and phase: Completed; Phase 1

Conditions: Healthy; Drug Abuse

Treatments: Drug: Placebos; Drug: Phentermine; Drug: Pitolisant

Study type: Interventional

Funder types: Other

Identifiers

NCT03152123

P16-02 / BF2.649

Details and patient eligibility

About

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.

Enrollment: 43 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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43 participants in 4 patient groups, including a placebo group

Pitolisant HCl, 40 mg

Experimental group

Description:

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)

Treatment:

Drug: Pitolisant

Pitolisant HCl, 240 mg

Experimental group

Description:

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)

Treatment:

Drug: Pitolisant

Phentermine HCl, 60 mg

Active Comparator group

Description:

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)

Treatment:

Drug: Phentermine

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebos