Evaluation of the Effect of Rifampin and Rabeprazole on the Pharmacokinetics 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

Population: Pharmacokinetic Parameter Population comprised of all participants for whom the Day 1 and Day 11 (Part 1) PK profiles of Camlipixant were adequately characterized, specifically, when administered alone and in combination with Rifampin (Part 1).

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

Population: Pharmacokinetic Parameter Population comprised of all participants for whom the Day 1 and Day 11 (Part 1) PK profiles of Camlipixant were adequately characterized, specifically, when administered alone and in combination with Rifampin (Part 1).

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

Population: Pharmacokinetic Parameter Population comprised of all participants for whom the Day 1 and Day 11 (Part 1) PK profiles of Camlipixant were adequately characterized, specifically, when administered alone and in combination with Rifampin (Part 1).

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

Population: Pharmacokinetic Parameter Population comprised of all participants for whom the Day 1 and Day 10 (Part 2) PK profiles of Camlipixant, were adequately characterized, specifically, when administered alone and in combination with Rabeprazole (Part 2).

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

Population: Pharmacokinetic Parameter Population comprised of all participants for whom the Day 1 and Day 10 (Part 2) PK profiles of Camlipixant, were adequately characterized, specifically, when administered alone and in combination with Rabeprazole (Part 2).

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

Population: Pharmacokinetic Parameter Population comprised of all participants for whom the Day 1 and Day 10 (Part 2) PK profiles of Camlipixant, were adequately characterized, specifically, when administered alone and in combination with Rabeprazole (Part 2).

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

Population: Pharmacokinetic Parameter Population comprised of all participants for whom the Day 1 and Day 11 (Part 1) PK profiles of Camlipixant were adequately characterized, specifically, when administered alone and in combination with Rifampin (Part 1).

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

Population: Pharmacokinetic Parameter Population comprised of all participants for whom the Day 1 and Day 11 (Part 1) PK profiles of Camlipixant were adequately characterized, specifically, when administered alone and in combination with Rifampin (Part 1).

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

Population: Safety population consisted of all participants who received at least one dose of any study drug.

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

Population: Safety population consisted of all participants who received at least one dose of any study drug.

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

Population: Safety population consisted of all participants who received at least one dose of any study drug.

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

Population: Safety population consisted of all participants who received at least one dose of any study drug.

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

Population: Safety population consisted of all participants who received at least one dose of any study drug.

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

Population: Safety population consisted of all participants who received at least one dose of any study drug.

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

Population: Safety population consisted of all participants who received at least one dose of any study drug.

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

Population: Safety population consisted of all participants who received at least one dose of any study drug.

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]

Population: Safety population consisted of all participants who received at least one dose of any study drug.

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

Population: Pharmacokinetic Parameter Population comprised of all participants for whom the Day 1 and Day 11 (Part 1) PK profiles of Camlipixant were adequately characterized, specifically, when administered alone and in combination with Rifampin (Part 1).

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

Population: Pharmacokinetic Parameter Population comprised of all participants for whom the Day 1 and Day 11 (Part 1) PK profiles of Camlipixant were adequately characterized, specifically, when administered alone and in combination with Rifampin (Part 1).

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

Population: Pharmacokinetic Parameter Population comprised of all participants for whom the Day 1 and Day 11 (Part 1) PK profiles of Camlipixant were adequately characterized, specifically, when administered alone and in combination with Rifampin (Part 1).

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

Population: Pharmacokinetic Parameter Population comprised of all participants for whom the Day 1 and Day 11 (Part 1) PK profiles of Camlipixant were adequately characterized, specifically, when administered alone and in combination with Rifampin (Part 1).

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

Population: Pharmacokinetic Parameter Population comprised of all participants for whom the Day 1 and Day 10 (Part 2) PK profiles of Camlipixant, were adequately characterized, specifically, when administered alone and in combination with Rabeprazole (Part 2).

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

Population: Pharmacokinetic Parameter Population comprised of all participants for whom the Day 1 and Day 10 (Part 2) PK profiles of Camlipixant, were adequately characterized, specifically, when administered alone and in combination with Rabeprazole (Part 2).

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

Population: Safety population consisted of all participants who received at least one dose of any study drug.

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

Population: Safety population consisted of all participants who received at least one dose of any study drug.

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

Population: Safety population consisted of all participants who received at least one dose of any study drug.

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

Population: Safety population consisted of all participants who received at least one dose of any study drug.

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

Population: Safety population consisted of all participants who received at least one dose of any study drug.

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

Population: Safety population consisted of all participants who received at least one dose of any study drug.

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

Population: Safety population consisted of all participants who received at least one dose of any study drug.

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

Population: Safety population consisted of all participants who received at least one dose of any study drug.

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]

Population: Safety population consisted of all participants who received at least one dose of any study drug.

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

Population: Pharmacokinetic Parameter Population comprised of all participants for whom the Day 1 and Day 10 (Part 2) PK profiles of Camlipixant, were adequately characterized, specifically, when administered alone and in combination with Rabeprazole (Part 2).

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

Population: Pharmacokinetic Parameter Population comprised of all participants for whom the Day 1 and Day 10 (Part 2) PK profiles of Camlipixant, were adequately characterized, specifically, when administered alone and in combination with Rabeprazole (Part 2).

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

Population: Pharmacokinetic Parameter Population comprised of all participants for whom the Day 1 and Day 10 (Part 2) PK profiles of Camlipixant, were adequately characterized, specifically, when administered alone and in combination with Rabeprazole (Part 2).

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

Population: Pharmacokinetic Parameter Population comprised of all participants for whom the Day 1 and Day 10 (Part 2) PK profiles of Camlipixant, were adequately characterized, specifically, when administered alone and in combination with Rabeprazole (Part 2).