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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Camlipixant will be administered
Rabeprazole will be administered
Rifampin will be administered.
GSK Investigational Site
Québec, Quebec, Canada
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
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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.
Time frame: 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: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to Day 12