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

Phase 1

Completed

Conditions: Cough
Healthy

Interventions: Drug: Camlipixant
Drug: Rifampin
Drug: Rabeprazole

Registration Number: NCT05899829

Lead Sponsor: Bellus Health Inc. - a GSK company

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 42

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part 1: Camlipixant 50 mg + Rifampin 600 mg	Camlipixant	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.
Part 2: Camlipixant 50 mg + Rabeprazole 20 mg	Camlipixant	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
Part 1: Camlipixant 50 mg + Rifampin 600 mg	Rifampin	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.
Part 2: Camlipixant 50 mg + Rabeprazole 20 mg	Rabeprazole	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

Primary Outcome Measures

Name	Time	Method
Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-Infinity]) of Camlipixant	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	Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.
Part 2: AUC(0-Infinity) of Camlipixant	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	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.
Part 1: Area Under the Plasma Concentration-time Curve From Time Zero Until the Last Observed Concentration (AUC[0-t]) of Camlipixant	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	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.
Part 2: AUC(0-t) of Camlipixant	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	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.
Part 1: Maximum Observed Concentration (Cmax) of Camlipixant	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	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.
Part 2: Cmax of Camlipixant	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	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.

Secondary Outcome Measures

Name	Time	Method
Part 1: Time to Reach Maximum Observed Concentration (Tmax) of Camlipixant	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	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.
Part 2: Tmax of Camlipixant	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	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.
Part 1: Terminal Elimination Half-Life (T1/2) Following Administration of Camlipixant	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	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.
Part 2: T1/2 Following Administration of Camlipixant	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	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.
Part 1: Percentage of AUC0-Infinity Due to Extrapolation From the Time of the Last Observed Concentration to Infinity (% AUC Extrapolation) of Camlipixant	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	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.
Part 2: % AUC Extrapolation of Camlipixant	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	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.
Part 1: Terminal Elimination Rate Constant of Camlipixant	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	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.
Part 2: Terminal Elimination Rate Constant of Camlipixant	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	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.
Part 1: Apparent Clearance (CL/F) of Camlipixant	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	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.
Part 2: CL/F of Camlipixant	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	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.
Part 1: Apparent Oral Volume of Distribution (Vz/F) of Camlipixant	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	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.
Part 2: Vz/F of Camlipixant	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	Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods.
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)	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]	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.
Part 2: Number of Participants With TEAEs, TESAEs and TEAEMIs	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]	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.
Part 1: Number of Participants With Abnormal Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) Findings	Day 4, Day 11, and Day 13	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.
Part 2: Number of Participants With Abnormal Clinically Significant Changes in 12-Lead ECG Findings	Day 4, Day 10, and Day 12	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.
Part 1: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP), and Heart Rate	Day 11 and Day 13	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.
Part 2: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: DBP, SBP, and Heart Rate	Day 10 and Day 12	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.
Part 1: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: Respiratory Rate and Oral Temperature	Day 13	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.
Part 2: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: Respiratory Rate and Oral Temperature	Day 12	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.
Part 1: Number of Participants With Abnormal Clinically Significant Changes in Physical Examination	Up to Day 13	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.
Part 2: Number of Participants With Abnormal Clinically Significant Changes in Physical Examination	Up to Day 12	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.
Part 1: Number of Participants With Abnormal Clinically Significant Changes in Hematology Parameters	Up to Day 13	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.
Part 2: Number of Participants With Abnormal Clinically Significant Changes in Hematology Parameters	Up to Day 12	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.
Part 1: Number of Participants With Abnormal Clinically Significant Changes in Clinical Chemistry Parameters	Up to Day 13	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.
Part 2: Number of Participants With Abnormal Clinically Significant Changes in Clinical Chemistry Parameters	Up to Day 12	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.
Part 1: Number of Participants With Abnormal Clinically Significant Changes in Coagulation Parameters	Up to Day 13	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.
Part 2: Number of Participants With Abnormal Clinically Significant Changes in Coagulation Parameters	Up to Day 12	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.
Part 1: Number of Participants With Abnormal Clinically Significant Changes in Urinalysis	Up to Day 13	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.
Part 2: Number of Participants With Abnormal Clinically Significant Changes in Urinalysis	Up to Day 12	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.