A Study in Healthy Male Subjects to Investigate Whether Administration of Rifampicin Can Affect the Fate of Clazosentan in the Body of Clazosentan

Study Overview
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Brief Summary
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A study in healthy male subjects to investigate whether administration of rifampicin can affect the fate in the body (amount and time of presence in the blood) of clazosentan

Official Title
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A Single-center, Randomized, Double-blind, Two-period Cross-over Study to Investigate the Effect of Rifampicin on the Pharmacokinetics of Clazosentan in Healthy Male Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Clazosentan
* Drug: Rifampicin
* Other: Saline (0.9% sodium chloride)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent in a language understandable to the subject prior to any study-mandated procedure. Healthy male subjects aged between 18 and 65 years (inclusive) at Screening. Body mass index (BMI) of 18.0 to 30.0 kg/m2 (inclusive) at Screening. Systolic blood pressure (SBP) 100-145 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and pulse rate 45-90 bpm (inclusive), measured on the same arm, after 5 min in the supine position at Screening and on Day -1 of the first Period. Healthy on the basis of physical examination, cardiovascular assessments and laboratory tests. Study-specific criteria - Acceptance for the duration of the study and for 3 months thereafter to use a condom and not to procreate. Exclusion Criteria: Previous exposure to clazosentan. Previous exposure to rifampicin within 3 months prior to Screening. Known hypersensitivity to clazosentan or rifampicin or treatments of the same class, or any of their excipients. Known hypersensitivity or allergy to natural rubber latex. Participation in a clinical study involving study treatment administration within 3 months prior to Screening or in more than 4 clinical studies within 1 year prior to Screening. History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to Screening. Positive results for hepatitis B surface antigen or hepatitis C virus antibody at Screening. Positive results from the HIV serology at Screening. Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

Ages Eligible for Study
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Minimum Age: 18 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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, double-blind, two-period, cross-over Phase 1 study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment sequence AB<br>Period A: Saline + clazosentan Period B: Rifampicin + clazosentan | Drug: Clazosentan<br>* Continuous i.v. infusion of 15 mg/h of clazosentan for 3 h<br>Drug: Rifampicin<br>* Single i.v. dose of 600 mg rifampicin for 30 min<br>Other: Saline (0.9% sodium chloride)<br>* Single i.v infusion of 500 mL saline for 30 min<br>|
| Experimental: Treatment sequence BA<br>Period B: Rifampicin + clazosentan Period A: Saline + clazosentan | Drug: Clazosentan<br>* Continuous i.v. infusion of 15 mg/h of clazosentan for 3 h<br>Drug: Rifampicin<br>* Single i.v. dose of 600 mg rifampicin for 30 min<br>Other: Saline (0.9% sodium chloride)<br>* Single i.v infusion of 500 mL saline for 30 min<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC from zero to time t of the last measured concentration above the limit of quantification | The plasma PK parameters of clazosentan will be derived by non-compartmental analysis of the plasma concentration-time profiles | 24 hours post treatment infusion initiation | 
| AUC from zero to infinity (AUC0-inf) | The plasma PK parameters of clazosentan will be derived by non-compartmental analysis of the plasma concentration-time profiles | 24 hours post treatment infusion initiation | 
| AUC from zero to 3 h (AUC0-3) | The plasma PK parameters of clazosentan will be derived by non-compartmental analysis of the plasma concentration-time profiles | 24 hours post treatment infusion initiation | 
| The maximum plasma concentration (Cmax) | The plasma PK parameters of clazosentan will be derived by non-compartmental analysis of the plasma concentration-time profiles | 24 hours post treatment infusion initiation | 
| Terminal half-life (t½) | The plasma PK parameters of clazosentan will be derived by non-compartmental analysis of the plasma concentration-time profiles | 24 hours post treatment infusion initiation | 
| Total body clearance (CL) | The plasma PK parameters of clazosentan will be derived by non-compartmental analysis of the plasma concentration-time profiles | 24 hours post treatment infusion initiation | 
| Volume of distribution at steady state (Vss) | The plasma PK parameters of clazosentan will be derived by non-compartmental analysis of the plasma concentration-time profiles | 24 hours post treatment infusion initiation |