Study to Assess the Absorption, Distribution, Metabolism and Excretion (ADME) of [14C]-Pitolisant in Healthy Male Volunteers

An Open Label, Single-Period Repeated Dose Study Designed to Assess the Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-Pitolisant, at Steady-State Conditions, in Healthy CYP2D6 Genotyped Male Subjects

The purpose of this study is to better define the absorption and elimination pathways, and circulating metabolites of Pitolisant at steady state using Pitolisant radiolabelled, in healthy CYP2D6 genotyped male subject.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Pitolisant; Radiation: [14C]-Pitolisant

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 26 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy males aged 30 to 65 years.
• Body mass index 18.0 to 35.0 kg/m2.
• Genotyped with regard to their CYP2D6 status.

Exclusion Criteria:

• Participation in a clinical research study within the previous 3 months
• Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 1999, shall participate in the study.
• Regular alcohol consumption in males >21 units per week.
• Current smokers and those who have smoked within the last 12 months.
• Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of <90 mL/min using the Cockcroft-Gault equation.
• Use of CYP2D6 inhibitors or inducers in the 28 days prior to IMP administration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pitolisant; Pitolisant, oral single dose administration, from Day1 to Day7.	Drug: Pitolisant
Experimental: [14C]-Pitolisant; [14C]-Pitolisant, oral single dose administration at Day8.	Radiation: [14C]-Pitolisant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mass balance recovery of total radioactivity (Ae) in urine, faeces and expired air.	from Day 8 (pre-dose) to 120 h post 14C-radioactivity dose
Peak Plasma Concentration (Cmax), pitolisant and major metabolites.	From Day 1 (pre-dose) until 168hours post last dose
Area under the plasma concentration versus time curve [AUC(0-tau), AUC(0-inf), %AUCextrap], pitolisant and major metabolites.	From Day 1 (pre-dose) until 168hours post last dose
Volume of distribution (Vz/F), pitolisant and major metabolites.	From Day 1 (pre-dose) until 168hours post last dose
Apparent clearance (Clss/F), pitolisant and major metabolites.	From Day 1 (pre-dose) until 168hours post last dose
The slope of the apparent elimination phase (lambda-z), pitolisant and major metabolites.	From Day 1 (pre-dose) until 168hours post last dose
The apparent elimination half-life (T½), pitolisant and major metabolites.	From Day 1 (pre-dose) until 168hours post last dose
Time to reach Cmax (Tmax), pitolisant and major metabolites.	From Day 1 (pre-dose) until 168hours post last dose

Collaborators and Investigators

• Sponsor: Bioprojet
• Investigators: Principal Investigator: Litza McKenzie, MD, Quotient Clinical; Study Director: Thierry Duvauchelle, MD, Bioprojet Pharma

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: October 6, 2016
• First Submitted That Met QC Criteria: October 7, 2016
• First Posted (Estimate): October 11, 2016

Study Record Updates

• Last Update Posted (Estimate): October 11, 2016
• Last Update Submitted That Met QC Criteria: October 7, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: P15-02 / Pitolisant; 2016-000748-32 (EudraCT Number)