Evaluation of the Effect of Rifampin and Rabeprazole on the Pharmacokinetics of Camlipixant

A Phase 1, 2-part, Open-label, Fixed-sequence Study Evaluating the Effect of Rifampin (Part 1) and Rabeprazole (Part 2) on the Pharmacokinetics of a Single Dose of Camlipixant (BLU-5937) 50 mg Tablet in Healthy Participants Under Fasting Conditions

This is a phase 1, 2-part, open-label, fixed-sequence study evaluating the effect of rifampin (part 1) and rabeprazole (part 2) on the pharmacokinetics of a single dose of camlipixant (BLU-5937) 50 mg tablet in healthy participants under fasting conditions.

Study Overview

• Status: Completed
• Conditions: Healthy; Cough
• Intervention / Treatment: Drug: Camlipixant; Drug: Rifampin; Drug: Rabeprazole

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Quebec City, Quebec, Canada, G1P 0A2
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy males or non-pregnant, non-lactating healthy females

Exclusion Criteria:

• History of clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disorder, as judged by the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Camlipixant 50 mg + Rifampin 600 mg; Participants will receive a single oral dose of camlipixant 50 milligram (mg) tablet on Day 1, followed by repeat oral doses (2*300 mg) of rifampin 600 mg capsules, once daily (QD) from Days 4 to 12, with co-administration of a single oral dose of 50 mg camlipixant tablet with rifampin capsules on Day 11. There will be a washout of at least 3 days between the dose of camlipixant on Day 1 and the dose of rifampin on Day 4.	Drug: Camlipixant; Camlipixant will be administered; Drug: Rifampin; Rifampin will be administered.
Experimental: Part 2: Camlipixant 50 mg + Rabeprazole 20 mg; Participants will receive a single oral dose of camlipixant 50 mg tablet on Day 1, followed by repeat oral doses of 20 mg rabeprazole enteric-coated tablets, once daily (QD) from Days 4 to 11, with co-administration of a single oral dose of 50 mg camlipixant tablet with rabeprazole enteric-coated tablet on Day 10. There will be a washout of at least 3 days between the dose of camlipixant on Day 1 and the dose of rabeprazole on Day 4	Drug: Camlipixant; Camlipixant will be administered; Drug: Rabeprazole; Rabeprazole will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-Infinity]) of Camlipixant	Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.	Pre-dose, 0.16, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 36, and 48 hours post-dose on Day 1 and Day 11
Part 2: AUC(0-Infinity) of Camlipixant	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.	Pre-dose, 0.16, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 36, and 48 hours post-dose on Day 1 and Day 10
Part 1: Area Under the Plasma Concentration-time Curve From Time Zero Until the Last Observed Concentration (AUC[0-t]) of Camlipixant	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.	Pre-dose, 0.16, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 36, and 48 hours post-dose on Day 1 and Day 11
Part 2: AUC(0-t) of Camlipixant	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.	Pre-dose, 0.16, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 36, and 48 hours post-dose on Day 1 and Day 10
Part 1: Maximum Observed Concentration (Cmax) of Camlipixant	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.	Pre-dose, 0.16, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 36, and 48 hours post-dose on Day 1 and Day 11
Part 2: Cmax of Camlipixant	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.	Pre-dose, 0.16, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 36, and 48 hours post-dose on Day 1 and Day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Time to Reach Maximum Observed Concentration (Tmax) of Camlipixant	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.	Pre-dose, 0.16, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 36, and 48 hours post-dose on Day 1 and Day 11
Part 2: Tmax of Camlipixant	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.	Pre-dose, 0.16, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 36, and 48 hours post-dose on Day 1 and Day 10
Part 1: Terminal Elimination Half-Life (T1/2) Following Administration of Camlipixant	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.	Pre-dose, 0.16, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 36, and 48 hours post-dose on Day 1 and Day 11
Part 2: T1/2 Following Administration of Camlipixant	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.	Pre-dose, 0.16, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 36, and 48 hours post-dose on Day 1 and Day 10
Part 1: Percentage of AUC0-Infinity Due to Extrapolation From the Time of the Last Observed Concentration to Infinity (% AUC Extrapolation) of Camlipixant	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods. Percentage of AUC extrapolation was calculated as [1 - (AUC0-t/AUC0-inf)] * 100.	Pre-dose, 0.16, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 36, and 48 hours post-dose on Day 1 and Day 11
Part 2: % AUC Extrapolation of Camlipixant	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods. Percentage of AUC extrapolation was calculated as [1 - (AUC0-t/AUC0-inf)] * 100.	Pre-dose, 0.16, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 36, and 48 hours post-dose on Day 1 and Day 10
Part 1: Terminal Elimination Rate Constant of Camlipixant	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.	Pre-dose, 0.16, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 36, and 48 hours post-dose on Day 1 and Day 11
Part 2: Terminal Elimination Rate Constant of Camlipixant	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.	Pre-dose, 0.16, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 36, and 48 hours post-dose on Day 1 and Day 10
Part 1: Apparent Clearance (CL/F) of Camlipixant	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.	Pre-dose, 0.16, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 36, and 48 hours post-dose on Day 1 and Day 11
Part 2: CL/F of Camlipixant	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.	Pre-dose, 0.16, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 36, and 48 hours post-dose on Day 1 and Day 10
Part 1: Apparent Oral Volume of Distribution (Vz/F) of Camlipixant	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.	Pre-dose, 0.16, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 36, and 48 hours post-dose on Day 1 and Day 11
Part 2: Vz/F of Camlipixant	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.	Pre-dose, 0.16, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 36, and 48 hours post-dose on Day 1 and Day 10
Part 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs) and Treatment-emergent Adverse Events of Medical Interest (TEAEMIs)	An adverse event (AE) is defined as any untoward medical occurrence in a participant who is administered a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. Serious adverse events (SAEs) are defined as any untoward medical occurrence that; at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function. Adverse events of medical interest (AEMIs) are AEs of scientific interest specific to the drug class. Treatment-emergent events (i.e., TEAEs, TESAEs and TEAEMIs) were defined as events that commence on or after the time of first study drug administration.	Up to Day 22 for Part1 (Day1 post-dose until Day4 pre-dose of rifampin [Camlipixant 50mg];From Day4 dosing until Day11 pre-dose of camlipixant [Rifampin 600mg];From camlipixant dosing on Day11 until end of study [Day 22] [Camlipixant 50mg+Rifampin 600mg]
Part 2: Number of Participants With TEAEs, TESAEs and TEAEMIs	An adverse event (AE) is defined as any untoward medical occurrence in a participant who is administered a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. Serious adverse events (SAEs) are defined as any untoward medical occurrence that; at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function. Adverse events of medical interest (AEMIs) are AEs of scientific interest specific to the drug class. Treatment-emergent events (i.e., TEAEs, TESAEs and TEAEMIs) were defined as events that commence on or after the time of first study drug administration.	Upto Day21 for Part2(Day1 postdose until Day4 predose of rabeprazole [Camlipixant 50mg];From Day4 dosing until Day10 predose of camlipixant [Rabeprazole 20mg];From camlipixant dosing on Day10 until end of study[Day21] [Camlipixant 50mg+Rabeprazole 20mg]
Part 1: Number of Participants With Abnormal Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) Findings	A 12-lead ECG was recorded with the participant in a semi-recumbent or supine position, after 5 minutes of rest using an ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for the number of participants with abnormal clinically significant 12-Lead ECG findings have been presented.	Day 4, Day 11, and Day 13
Part 2: Number of Participants With Abnormal Clinically Significant Changes in 12-Lead ECG Findings	A 12-lead ECG was recorded with the participant in a semi-recumbent or supine position, after 5 minutes of rest using an ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for the number of participants with abnormal clinically significant 12-Lead ECG findings have been presented.	Day 4, Day 10, and Day 12
Part 1: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP), and Heart Rate	Vital signs including diastolic blood pressure (DBP), systolic Blood Pressure (SBP), and heart rate were measured in a sitting position after resting for at least 5 minutes. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for the number of participants with abnormal clinically significant changes for vital signs have been presented.	Day 11 and Day 13
Part 2: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: DBP, SBP, and Heart Rate	Vital signs including DBP, SBP, and heart rate were measured in a sitting position after resting for at least 5 minutes. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for the number of participants with abnormal clinically significant changes for vital signs have been presented.	Day 10 and Day 12
Part 1: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: Respiratory Rate and Oral Temperature	Vital signs including respiratory rate and oral temperature were measured after resting for at least 5 minutes in a sitting position. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for the number of participants with abnormal clinically significant changes for vital signs have been presented.	Day 13
Part 2: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: Respiratory Rate and Oral Temperature	Vital signs including respiratory rate and oral temperature were measured after resting for at least 5 minutes in a sitting position. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for the number of participants with abnormal clinically significant changes for vital signs have been presented.	Day 12
Part 1: Number of Participants With Abnormal Clinically Significant Changes in Physical Examination	Physical examination included assessment of the head, eyes, ears, nose, throat, neck, chest, lungs, abdomen, musculoskeletal, dermatological, cardiovascular/peripheral vascular, and general neurological examination. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for the number of participants with abnormal clinically significant changes in physical examination has been presented.	Up to Day 13
Part 2: Number of Participants With Abnormal Clinically Significant Changes in Physical Examination	Physical examination included assessment of the head, eyes, ears, nose, throat, neck, chest, lungs, abdomen, musculoskeletal, dermatological, cardiovascular/peripheral vascular, and general neurological examination. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for the number of participants with abnormal clinically significant changes in physical examination has been presented.	Up to Day 12
Part 1: Number of Participants With Abnormal Clinically Significant Changes in Hematology Parameters	Blood samples were collected to analyze hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Hematocrit, Hemoglobin, Platelets, and Erythrocytes. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with abnormal clinically significant changes in hematology parameters were reported.	Up to Day 13
Part 2: Number of Participants With Abnormal Clinically Significant Changes in Hematology Parameters	Blood samples were collected to analyze hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Hematocrit, Hemoglobin, Platelets, and Erythrocytes. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with abnormal clinically significant changes in hematology parameters were reported.	Up to Day 12
Part 1: Number of Participants With Abnormal Clinically Significant Changes in Clinical Chemistry Parameters	Blood samples were collected to analyze clinical chemical parameters: albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, calcium, chloride, creatinine kinase, creatinine, gamma glutamyl transferase, glucose, phosphate, potassium, sodium, total, direct, and indirect bilirubin, protein, urea, and urate. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of Participants with abnormal clinically significant changes in clinical chemistry parameters were reported.	Up to Day 13
Part 2: Number of Participants With Abnormal Clinically Significant Changes in Clinical Chemistry Parameters	Blood samples were collected to analyze clinical chemical parameters: albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, calcium, chloride, creatinine kinase, creatinine, gamma glutamyl transferase, glucose, phosphate, potassium, sodium, total, direct, and indirect bilirubin, protein, urea, and urate. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of Participants with abnormal clinically significant changes in clinical chemistry parameters were reported.	Up to Day 12
Part 1: Number of Participants With Abnormal Clinically Significant Changes in Coagulation Parameters	Blood samples were collected to analyze coagulation parameters: activated partial thromboplastin time, prothrombin time international (Intl.) normalized ratio, and prothrombin time. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of Participants with abnormal clinically significant changes in coagulation parameters were reported.	Up to Day 13
Part 2: Number of Participants With Abnormal Clinically Significant Changes in Coagulation Parameters	Blood samples were collected to analyze coagulation parameters: activated partial thromboplastin time, prothrombin time international (Intl.) normalized ratio, and prothrombin time. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of Participants with abnormal clinically significant changes in coagulation parameters were reported.	Up to Day 12
Part 1: Number of Participants With Abnormal Clinically Significant Changes in Urinalysis	Urine samples were collected to analyze urinalysis parameters: specific gravity and potential of hydrogen (pH). Bilirubin, blood (occult), glucose, ketones, leukocyte esterase, nitrite, protein, urobilinogen were analyzed by dipstick. The dipstick test gives results in a semi-quantitative manner, and results can be read as Negative, Trace, 1+, 2+ indicating proportional concentrations in the urine sample. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of Participants with abnormal clinically significant changes in urinalysis parameters were reported.	Up to Day 13
Part 2: Number of Participants With Abnormal Clinically Significant Changes in Urinalysis	Urine samples were collected to analyze urinalysis parameters: specific gravity and potential of hydrogen (pH). Bilirubin, blood (occult), glucose, ketones, leukocyte esterase, nitrite, protein, urobilinogen were analyzed by dipstick. The dipstick test gives results in a semi-quantitative manner, and results can be read as Negative, Trace, 1+, 2+ indicating proportional concentrations in the urine sample. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of Participants with abnormal clinically significant changes in urinalysis parameters were reported.	Up to Day 12

Collaborators and Investigators

• Sponsor: Bellus Health Inc. - a GSK company

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2023
• Primary Completion (Actual): August 8, 2023
• Study Completion (Actual): August 8, 2023

Study Registration Dates

• First Submitted: June 2, 2023
• First Submitted That Met QC Criteria: June 2, 2023
• First Posted (Actual): June 12, 2023

Study Record Updates

• Last Update Posted (Estimated): December 4, 2024
• Last Update Submitted That Met QC Criteria: November 26, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Bacterial Agents; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antibiotics, Antitubercular; Antitubercular Agents; Leprostatic Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Cytochrome P-450 CYP3A Inducers; Rifampin; Rabeprazole
• Other Study ID Numbers: 221853; BUS-P1-11 (Other Identifier: Bellus Health Inc)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No