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

NCT03596294 | Completed Phase 1 FDA Drug

• 2 other identifiers: ID-054-1062018-001607-36
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (7)

• 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

Study Arms (2)

Treatment sequence AB

EXPERIMENTAL

Period A: Saline + clazosentan Period B: Rifampicin + clazosentan

Drug: Clazosentan; Drug: Rifampicin; Other: Saline (0.9% sodium chloride)

Treatment sequence BA

EXPERIMENTAL

Period B: Rifampicin + clazosentan Period A: Saline + clazosentan

Drug: Clazosentan; Drug: Rifampicin; Other: Saline (0.9% sodium chloride)

Interventions

Clazosentan DRUG

Continuous i.v. infusion of 15 mg/h of clazosentan for 3 h

Treatment sequence AB; Treatment sequence BA

Rifampicin DRUG

Single i.v. dose of 600 mg rifampicin for 30 min

Treatment sequence AB; Treatment sequence BA

Saline (0.9% sodium chloride) OTHER

Single i.v infusion of 500 mL saline for 30 min

Treatment sequence AB; Treatment sequence BA

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (1)

QPS Netherlands B.V.

Groningen, 9713 GZ, Netherlands

Location

MeSH Terms

Interventions

clazosentan; Rifampin; Sodium Chloride

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Clinical Trials

  Idorsia Pharmaceuticals Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, two-period, cross-over Phase 1 study

Study Record Dates

• First Submitted: July 5, 2018
• First Posted: July 23, 2018
• Study Start: July 19, 2018
• Primary Completion: August 3, 2018
• Study Completion: August 3, 2018
• Last Updated: October 23, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)