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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Pitolisant
* Radiation: [14C]-Pitolisant


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |