Cough, Healthy
Conditions
Brief summary
This is a phase 1, 2-part, open-label, fixed-sequence study evaluating potential drug-drug interactions between gemfibrozil (part 1) or dabigatran etexilate (part 2) and camlipixant (BLU-5937) 50 mg tablet in healthy participants under fasting conditions.
Interventions
DRUGCamlipixant
Camlipixant will be administered
DRUGDabigatran etexilate
Dabigatran etexilate will be administered
DRUGGemfibrozil
Gemfibrozil will be administered.
Sponsors
Bellus Health Inc. - a GSK company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC-inf) of Camlipixant | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9 | 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 Concentration-time Curve From Time Zero Until the Last Observed Concentration (AUC[0-t]) of Camlipixant | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9 | Blood samples were collected at indicated time points for PK analysis of Camlipixant. PK analysis was conducted using standard non-compartmental methods. |
| Part 1: Maximal Observed Concentration (Cmax) of Camlipixant | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9 | 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-Infinity) of Free Dabigatran | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10 | Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods. |
| Part 2: AUC(0-t) of Free Dabigatran | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10 | Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods. |
| Part 2: Cmax of Free Dabigatran | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10 | Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods. |
| Part 2: AUC(0-Infinity) of Total Dabigatran | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10 | Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods. |
| Part 2: AUC(0-t) of Total Dabigatran | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10 | Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods. |
| Part 2: Cmax of Total Dabigatran | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10 | Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Kel Free Dabigatran | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10 | Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods. |
| Part 2: CL/F Free Dabigatran | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10 | Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods. |
| Part 2: Vz/F Free Dabigatran | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10 | Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods. |
| Part 2: Tmax of Total Dabigatran | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10 | Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods. |
| Part 2: T1/2 Following Administration of Total Dabigatran | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10 | Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods. |
| Part 2: Percentage of AUC0-Infinity Due to Extrapolation From the Time of the Last Observed Concentration to Infinity (%AUC Extrapolation) of Total Dabigatran | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10 | Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods. Percentage of AUC extrapolation was calculated as \[1 - (AUC0-t/AUC0-inf)\] \* 100. |
| Part 2: Kel of Total Dabigatran | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10 | Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods. |
| Part 2: CL/F of Total Dabigatran | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10 | Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods. |
| Part 2: Vz/F of Total Dabigatran | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10 | Blood samples were collected at indicated time points for PK analysis of Dabigatran. 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) | Day 1 post-dose until Day 5 pre-dose of gemfibrozil [camlipixant 50mg]; from Day 5 dosing until Day 9 pre-dose of camlipixant [gemfibrozil 600mg]; from camlipixant dosing on Day 9 until end of study [Day 21] [camlipixant 50mg+gemfibrozil 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 inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per medical and scientific judgement. Adverse events of medical interest (AEMIs) are AEs of scientific interest specific to the drug class. AEMIs for this study includes the following, but not limited to taste disturbances (dysgeusia, hypogeusia, ageusia), oral paresthesia and oral hypoesthesia 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 | Day1 postdose until Day5 predose of camlipixant [dabigatran etexilate 150mg];from Day5 dosing until Day10 predose of dabigatran [camlipixant 50mg];from dabigatran dosing on Day10 until end of study [Day 22][dabigatran etexilate 150mg+camlipixant 50mg] | 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 inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per medical and scientific judgement. Adverse events of medical interest (AEMIs) are AEs of scientific interest specific to the drug class. AEMIs for this study includes the following, but not limited to: taste disturbances (dysgeusia, hypogeusia, ageusia), oral paresthesia and oral hypoesthesia 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 5, Day 9 pre-dose and 1 hour post-dose, 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 2: Number of Participants With Abnormal Clinically Significant Changes in 12-Lead ECG Findings | Day 5, Day 10 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 1: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP), and Heart Rate | Day 9 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 2: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: DBP, SBP, and Heart Rate | Day 10 and Day 13 | 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 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 2: 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 1: Number of Participants With Abnormal Clinically Significant Changes During 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: Time to Reach Maximum Observed Concentration (Tmax) of Camlipixant | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9 | 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 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 2: 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 1: 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 2: 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 1: 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 normalized ratio (INR), 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 13 | Blood samples were collected to analyze coagulation parameters: activated partial thromboplastin time, prothrombin time international normalized ratio (INR), 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 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. |
| Part 2: 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 During 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 1: Terminal Elimination Half-Life (T1/2) Following Administration of Camlipixant | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9 | 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, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9 | 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 (Kel) | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9 | 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, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9 | 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 Volume of Distribution (Vz/F) of Camlipixant | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9 | 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 Free Dabigatran | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10 | Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods. |
| Part 2: T1/2 Following Administration Free Dabigatran | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10 | Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods. |
| Part 2: Percentage of AUC0-Infinity Due to Extrapolation From the Time of the Last Observed Concentration to Infinity (%AUC Extrapolation) of Free Dabigatran | Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10 | Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods. Percentage of AUC extrapolation was calculated as \[1 - (AUC0-t/AUC0-inf)\] \* 100. |
Countries
Canada
Participant flow
Pre-assignment details
A total of 45 participants were enrolled in the study (25 participants in Part 1 and 20 participants in Part 2). Only 32 participants (13 participants were never dosed) were dosed into the study to receive either camlipixant + gemfibrozil or dabigatran etexilate+ camlipixant creating the Safety Population. (The safety population included all participants who received at least one dose of any study drug).
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg Participants received a single oral dose of camlipixant 50 milligram (mg) tablet on Day 1, followed by repeat oral doses of gemfibrozil 600 mg tablet twice daily (BID), every 12 hours, (total daily dose of 1200 mg) on Days 5 to 11, with co-administration of a single oral dose of camlipixant 50 mg tablet with the gemfibrozil on Day 9. There was a washout of at least 4 days between the dose of camlipixant on Day 1 and the dose of gemfibrozil on Day 5. | 16 |
| Part 2: Dabigatran Etexilate 150 mg + Camlipixant 50 mg Participants received single oral dose of dabigatran etexilate 150 mg capsule on Day 1, followed by repeated oral doses of camlipixant 50 mg tablet twice daily (BID) (total daily dose of 100 mg) from Days 5 to 9, with co-administration of a single oral dose of dabigatran etexilate 150 mg capsule with the morning dose of camlipixant on Day 10. There was a washout of at least 4 days between the dose of dabigatran etexilate on Day 1 and the dose of camlipixant on Day 5. | 16 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Part 1 (Up to Day 21) | Adverse Event | 1 | 0 |
| Part 1 (Up to Day 21) | Enrolled but did not receive study treatment | 9 | 0 |
| Part 2 (Up to Day 22) | Adverse Event | 0 | 2 |
| Part 2 (Up to Day 22) | Enrolled but did not receive study treatment | 0 | 4 |
Baseline characteristics
| Characteristic | Part 2: Dabigatran Etexilate 150 mg + Camlipixant 50 mg | Total | Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg |
|---|---|---|---|
| Age, Customized 23 to 54 years | 16 Participants | 32 Participants | 16 Participants |
| Race/Ethnicity, Customized All Other Races | 2 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 14 Participants | 28 Participants | 14 Participants |
| Sex: Female, Male Female | 7 Participants | 14 Participants | 7 Participants |
| Sex: Female, Male Male | 9 Participants | 18 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 15 | 0 / 14 |
| other Total, other adverse events | 1 / 16 | 6 / 16 | 5 / 16 | 4 / 16 | 6 / 15 | 0 / 14 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 1 / 16 | 0 / 16 | 0 / 15 | 0 / 14 |
Outcome results
Primary
Part 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC-inf) 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, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9
Population: The PK parameter Population included all participants for whom the Day 1 and Day 9 PK profiles of the camlipixant could be adequately characterized, specifically, when administered alone and in combination with gemfibrozil (Part 1)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC-inf) of Camlipixant | Day 1 | 4886.66 Hours*nanograms per milliliter | Geometric Coefficient of Variation 28.69 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC-inf) of Camlipixant | Day 9 | 10642.07 Hours*nanograms per milliliter | Geometric Coefficient of Variation 24.17 |
Primary
Part 1: Area Under the 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, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9
Population: The PK parameter Population included all participants for whom the Day 1 and Day 9 PK profiles of the camlipixant could be adequately characterized, specifically, when administered alone and in combination with gemfibrozil (Part 1)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Area Under the Concentration-time Curve From Time Zero Until the Last Observed Concentration (AUC[0-t]) of Camlipixant | Day 1 | 4846.83 Hours*nanograms per milliliter | Geometric Coefficient of Variation 28.84 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Area Under the Concentration-time Curve From Time Zero Until the Last Observed Concentration (AUC[0-t]) of Camlipixant | Day 9 | 10541.57 Hours*nanograms per milliliter | Geometric Coefficient of Variation 24.44 |
Primary
Part 1: Maximal 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, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9
Population: The PK parameter Population included all participants for whom the Day 1 and Day 9 PK profiles of the camlipixant could be adequately characterized, specifically, when administered alone and in combination with gemfibrozil (Part 1)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Maximal Observed Concentration (Cmax) of Camlipixant | Day 1 | 1078 Nanograms per milliliter | Geometric Coefficient of Variation 25.02 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Maximal Observed Concentration (Cmax) of Camlipixant | Day 9 | 1303 Nanograms per milliliter | Geometric Coefficient of Variation 25.65 |
Primary
Part 2: AUC(0-Infinity) of Free Dabigatran
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Population: The PK parameter Population included all participants for whom the Day 1 and Day 10 PK profiles of the dabigatran could be adequately characterized, specifically, when administered alone and in combination with camlipixant (Part 2). Only those participants who were measured and analyzed (i.e., contributed data reported in table) were included in 'Overall Number of Participants Analyzed' field.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: AUC(0-Infinity) of Free Dabigatran | Day 1 | 943.49 Hours*nanograms per milliliter | Geometric Coefficient of Variation 52.12 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: AUC(0-Infinity) of Free Dabigatran | Day 10 | 1055.20 Hours*nanograms per milliliter | Geometric Coefficient of Variation 43.81 |
Primary
Part 2: AUC(0-Infinity) of Total Dabigatran
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Population: The PK parameter Population included all participants for whom the Day 1 and Day 10 PK profiles of the dabigatran could be adequately characterized, specifically, when administered alone and in combination with camlipixant (Part 2). Only those participants who were measured and analyzed (i.e., contributed data reported in table) were included in 'Overall Number of Participants Analyzed' field.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: AUC(0-Infinity) of Total Dabigatran | Day 1 | 1165.82 Hours*nanograms per milliliter | Geometric Coefficient of Variation 52.34 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: AUC(0-Infinity) of Total Dabigatran | Day 10 | 1339.35 Hours*nanograms per milliliter | Geometric Coefficient of Variation 41.21 |
Primary
Part 2: AUC(0-t) of Free Dabigatran
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Population: The PK parameter Population included all participants for whom the Day 1 and Day 10 PK profiles of the dabigatran could be adequately characterized, specifically, when administered alone and in combination with camlipixant (Part 2). Only those participants who were measured and analyzed (i.e., contributed data reported in table) were included in 'Overall Number of Participants Analyzed' field.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: AUC(0-t) of Free Dabigatran | Day 1 | 920.18 Hours*nanograms per milliliter | Geometric Coefficient of Variation 53.11 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: AUC(0-t) of Free Dabigatran | Day 10 | 1031.89 Hours*nanograms per milliliter | Geometric Coefficient of Variation 45.03 |
Primary
Part 2: AUC(0-t) of Total Dabigatran
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Population: The PK parameter Population included all participants for whom the Day 1 and Day 10 PK profiles of the dabigatran could be adequately characterized, specifically, when administered alone and in combination with camlipixant (Part 2). Only those participants who were measured and analyzed (i.e., contributed data reported in table) were included in 'Overall Number of Participants Analyzed' field.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: AUC(0-t) of Total Dabigatran | Day 1 | 1139.80 Hours*nanograms per milliliter | Geometric Coefficient of Variation 53.51 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: AUC(0-t) of Total Dabigatran | Day 10 | 1316.80 Hours*nanograms per milliliter | Geometric Coefficient of Variation 41.83 |
Primary
Part 2: Cmax of Free Dabigatran
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Population: The PK parameter Population included all participants for whom the Day 1 and Day 10 PK profiles of the dabigatran could be adequately characterized, specifically, when administered alone and in combination with camlipixant (Part 2). Only those participants who were measured and analyzed (i.e., contributed data reported in table) were included in 'Overall Number of Participants Analyzed' field.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Cmax of Free Dabigatran | Day 1 | 110 Nanograms per milliliter | Geometric Coefficient of Variation 53.53 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Cmax of Free Dabigatran | Day 10 | 125 Nanograms per milliliter | Geometric Coefficient of Variation 47.75 |
Primary
Part 2: Cmax of Total Dabigatran
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Population: The PK parameter Population included all participants for whom the Day 1 and Day 10 PK profiles of the dabigatran could be adequately characterized, specifically, when administered alone and in combination with camlipixant (Part 2). Only those participants who were measured and analyzed (i.e., contributed data reported in table) were included in 'Overall Number of Participants Analyzed' field.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Cmax of Total Dabigatran | Day 1 | 135 Nanograms per milliliter | Geometric Coefficient of Variation 54.2 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Cmax of Total Dabigatran | Day 10 | 160 Nanograms per milliliter | Geometric Coefficient of Variation 42.42 |
Secondary
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, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9
Population: The PK parameter Population included all participants for whom the Day 1 and Day 9 PK profiles of the camlipixant could be adequately characterized, specifically, when administered alone and in combination with gemfibrozil (Part 1)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Apparent Clearance (CL/F) of Camlipixant | Day 1 | 10.23 Liters per hour | Geometric Coefficient of Variation 28.69 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Apparent Clearance (CL/F) of Camlipixant | Day 9 | 4.70 Liters per hour | Geometric Coefficient of Variation 24.17 |
Secondary
Part 1: Apparent 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, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9
Population: The PK parameter Population included all participants for whom the Day 1 and Day 9 PK profiles of the camlipixant could be adequately characterized, specifically, when administered alone and in combination with gemfibrozil (Part 1)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Apparent Volume of Distribution (Vz/F) of Camlipixant | Day 9 | 64.80 Liters | Geometric Coefficient of Variation 23.69 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Apparent Volume of Distribution (Vz/F) of Camlipixant | Day 1 | 82.06 Liters | Geometric Coefficient of Variation 22.57 |
Secondary
Part 1: Number of Participants With Abnormal Clinically Significant Changes During 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
Population: Safety population consisted of all participants who received at least one dose of any study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Number of Participants With Abnormal Clinically Significant Changes During Physical Examination | 1 Participants |
Secondary
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 5, Day 9 pre-dose and 1 hour post-dose, Day 12
Population: Safety population consisted of all participants who received at least one dose of any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Number of Participants With Abnormal Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) Findings | Day 5 | 0 Participants |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Number of Participants With Abnormal Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) Findings | Day 9, Pre-dose | 0 Participants |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Number of Participants With Abnormal Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) Findings | Day 9,1-Hour Post-dose | 0 Participants |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Number of Participants With Abnormal Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) Findings | Day 12 | 0 Participants |
Secondary
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 12
Population: Safety population consisted of all participants who received at least one dose of any study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Number of Participants With Abnormal Clinically Significant Changes in Clinical Chemistry Parameters | 3 Participants |
Secondary
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 normalized ratio (INR), 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Number of Participants With Abnormal Clinically Significant Changes in Coagulation Parameters | 0 Participants |
Secondary
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 12
Population: Safety population consisted of all participants who received at least one dose of any study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Number of Participants With Abnormal Clinically Significant Changes in Hematology Parameters | 0 Participants |
Secondary
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 12
Population: Safety population consisted of all participants who received at least one dose of any study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Number of Participants With Abnormal Clinically Significant Changes in Urinalysis | 0 Participants |
Secondary
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 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 9 and Day 12
Population: Safety population consisted of all participants who received at least one dose of any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | 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 9 | 0 Participants |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | 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 12 | 0 Participants |
Secondary
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 12
Population: Safety population consisted of all participants who received at least one dose of any study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: Respiratory Rate and Oral Temperature | 0 Participants |
Secondary
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 inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per medical and scientific judgement. Adverse events of medical interest (AEMIs) are AEs of scientific interest specific to the drug class. AEMIs for this study includes the following, but not limited to taste disturbances (dysgeusia, hypogeusia, ageusia), oral paresthesia and oral hypoesthesia 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: Day 1 post-dose until Day 5 pre-dose of gemfibrozil [camlipixant 50mg]; from Day 5 dosing until Day 9 pre-dose of camlipixant [gemfibrozil 600mg]; from camlipixant dosing on Day 9 until end of study [Day 21] [camlipixant 50mg+gemfibrozil 600mg]
Population: Safety Population consisted of all participants who received at least one dose of any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | 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) | TESAEs | 0 Participants |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | 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) | TEAEs | 1 Participants |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | 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) | TEAEMIs | 0 Participants |
| Part 1: Gemfibrozil 600 mg | 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) | TESAEs | 0 Participants |
| Part 1: Gemfibrozil 600 mg | 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) | TEAEs | 6 Participants |
| Part 1: Gemfibrozil 600 mg | 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) | TEAEMIs | 0 Participants |
| Part 1: Camlipixant 50 mg+ Gemfibrozil 600 mg | 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) | TEAEs | 5 Participants |
| Part 1: Camlipixant 50 mg+ Gemfibrozil 600 mg | 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) | TEAEMIs | 1 Participants |
| Part 1: Camlipixant 50 mg+ Gemfibrozil 600 mg | 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) | TESAEs | 1 Participants |
Secondary
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, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9
Population: The PK parameter Population included all participants for whom the Day 1 and Day 9 PK profiles of the camlipixant could be adequately characterized, specifically, when administered alone and in combination with gemfibrozil (Part 1)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Percentage of AUC0-Infinity Due to Extrapolation From the Time of the Last Observed Concentration to Infinity (%AUC Extrapolation) of Camlipixant | Day 1 | 0.58 Percentage of AUC extrapolation | Geometric Coefficient of Variation 104.04 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Percentage of AUC0-Infinity Due to Extrapolation From the Time of the Last Observed Concentration to Infinity (%AUC Extrapolation) of Camlipixant | Day 9 | 0.59 Percentage of AUC extrapolation | Geometric Coefficient of Variation 109.24 |
Secondary
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, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9
Population: The PK parameter Population included all participants for whom the Day 1 and Day 9 PK profiles of the camlipixant could be adequately characterized, specifically, when administered alone and in combination with gemfibrozil (Part 1)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Terminal Elimination Half-Life (T1/2) Following Administration of Camlipixant | Day 1 | 5.56 Hours | Geometric Coefficient of Variation 31.8 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Terminal Elimination Half-Life (T1/2) Following Administration of Camlipixant | Day 9 | 9.56 Hours | Geometric Coefficient of Variation 18.6 |
Secondary
Part 1: Terminal Elimination Rate Constant of Camlipixant (Kel)
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, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9
Population: The PK parameter Population included all participants for whom the Day 1 and Day 9 PK profiles of the camlipixant could be adequately characterized, specifically, when administered alone and in combination with gemfibrozil (Part 1)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Terminal Elimination Rate Constant of Camlipixant (Kel) | Day 1 | 0.1247 h^-1 | Geometric Coefficient of Variation 31.8 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Terminal Elimination Rate Constant of Camlipixant (Kel) | Day 9 | 0.0725 h^-1 | Geometric Coefficient of Variation 18.6 |
Secondary
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, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 15, 18, 24, 48, 72 hours post-dose on Day 1 and Day 9
Population: The PK parameter Population included all participants for whom the Day 1 and Day 9 PK profiles of the camlipixant could be adequately characterized, specifically, when administered alone and in combination with gemfibrozil (Part 1)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Time to Reach Maximum Observed Concentration (Tmax) of Camlipixant | Day 1 | 0.750 Hours |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 1: Time to Reach Maximum Observed Concentration (Tmax) of Camlipixant | Day 9 | 0.750 Hours |
Secondary
Part 2: CL/F Free Dabigatran
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Population: The PK parameter Population included all participants for whom the Day 1 and Day 10 PK profiles of the dabigatran could be adequately characterized, specifically, when administered alone and in combination with camlipixant (Part 2). Only those participants who were measured and analyzed (i.e., contributed data reported in table) were included in 'Overall Number of Participants Analyzed' field.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: CL/F Free Dabigatran | Day 1 | 158.98 Liters per hour | Geometric Coefficient of Variation 52.12 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: CL/F Free Dabigatran | Day 10 | 142.15 Liters per hour | Geometric Coefficient of Variation 43.81 |
Secondary
Part 2: CL/F of Total Dabigatran
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Population: The PK parameter Population included all participants for whom the Day 1 and Day 10 PK profiles of the dabigatran could be adequately characterized, specifically, when administered alone and in combination with camlipixant (Part 2). Only those participants who were measured and analyzed (i.e., contributed data reported in table) were included in 'Overall Number of Participants Analyzed' field.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: CL/F of Total Dabigatran | Day 1 | 128.66 Liters per hour | Geometric Coefficient of Variation 52.34 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: CL/F of Total Dabigatran | Day 10 | 111.99 Liters per hour | Geometric Coefficient of Variation 41.21 |
Secondary
Part 2: Kel Free Dabigatran
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Population: The PK parameter Population included all participants for whom the Day 1 and Day 10 PK profiles of the dabigatran could be adequately characterized, specifically, when administered alone and in combination with camlipixant (Part 2). Only those participants who were measured and analyzed (i.e., contributed data reported in table) were included in 'Overall Number of Participants Analyzed' field.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Kel Free Dabigatran | Day 1 | 0.0660 h^-1 | Geometric Coefficient of Variation 18.23 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Kel Free Dabigatran | Day 10 | 0.0755 h^-1 | Geometric Coefficient of Variation 9.16 |
Secondary
Part 2: Kel of Total Dabigatran
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Population: The PK parameter Population included all participants for whom the Day 1 and Day 10 PK profiles of the dabigatran could be adequately characterized, specifically, when administered alone and in combination with camlipixant (Part 2). Only those participants who were measured and analyzed (i.e., contributed data reported in table) were included in 'Overall Number of Participants Analyzed' field.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Kel of Total Dabigatran | Day 1 | 0.0628 h^-1 | Geometric Coefficient of Variation 30.01 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Kel of Total Dabigatran | Day 10 | 0.0679 h^-1 | Geometric Coefficient of Variation 16.9 |
Secondary
Part 2: Number of Participants With Abnormal Clinically Significant Changes During 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
Population: Safety population consisted of all participants who received at least one dose of any study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Number of Participants With Abnormal Clinically Significant Changes During Physical Examination | 0 Participants |
Secondary
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 5, Day 10 and Day 13
Population: Safety population consisted of all participants who received at least one dose of any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Number of Participants With Abnormal Clinically Significant Changes in 12-Lead ECG Findings | Day 5 | 0 Participants |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Number of Participants With Abnormal Clinically Significant Changes in 12-Lead ECG Findings | Day 10 | 0 Participants |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Number of Participants With Abnormal Clinically Significant Changes in 12-Lead ECG Findings | Day 13 | 0 Participants |
Secondary
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 13
Population: Safety population consisted of all participants who received at least one dose of any study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Number of Participants With Abnormal Clinically Significant Changes in Clinical Chemistry Parameters | 1 Participants |
Secondary
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 normalized ratio (INR), 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Number of Participants With Abnormal Clinically Significant Changes in Coagulation Parameters | 0 Participants |
Secondary
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 13
Population: Safety population consisted of all participants who received at least one dose of any study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Number of Participants With Abnormal Clinically Significant Changes in Hematology Parameters | 0 Participants |
Secondary
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 13
Population: Safety population consisted of all participants who received at least one dose of any study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Number of Participants With Abnormal Clinically Significant Changes in Urinalysis | 0 Participants |
Secondary
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 13
Population: Safety population consisted of all participants who received at least one dose of any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: DBP, SBP, and Heart Rate | Day 10 | 0 Participants |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: DBP, SBP, and Heart Rate | Day 13 | 0 Participants |
Secondary
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 13
Population: Safety population consisted of all participants who received at least one dose of any study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: Respiratory Rate and Oral Temperature | 0 Participants |
Secondary
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 inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per medical and scientific judgement. Adverse events of medical interest (AEMIs) are AEs of scientific interest specific to the drug class. AEMIs for this study includes the following, but not limited to: taste disturbances (dysgeusia, hypogeusia, ageusia), oral paresthesia and oral hypoesthesia 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: Day1 postdose until Day5 predose of camlipixant [dabigatran etexilate 150mg];from Day5 dosing until Day10 predose of dabigatran [camlipixant 50mg];from dabigatran dosing on Day10 until end of study [Day 22][dabigatran etexilate 150mg+camlipixant 50mg]
Population: Safety population consisted of all participants who received at least one dose of any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Number of Participants With TEAEs, TESAEs and TEAEMIs | TESAEs | 0 Participants |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Number of Participants With TEAEs, TESAEs and TEAEMIs | TEAEs | 4 Participants |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Number of Participants With TEAEs, TESAEs and TEAEMIs | TEAEMIs | 0 Participants |
| Part 1: Gemfibrozil 600 mg | Part 2: Number of Participants With TEAEs, TESAEs and TEAEMIs | TESAEs | 0 Participants |
| Part 1: Gemfibrozil 600 mg | Part 2: Number of Participants With TEAEs, TESAEs and TEAEMIs | TEAEs | 6 Participants |
| Part 1: Gemfibrozil 600 mg | Part 2: Number of Participants With TEAEs, TESAEs and TEAEMIs | TEAEMIs | 0 Participants |
| Part 1: Camlipixant 50 mg+ Gemfibrozil 600 mg | Part 2: Number of Participants With TEAEs, TESAEs and TEAEMIs | TEAEs | 0 Participants |
| Part 1: Camlipixant 50 mg+ Gemfibrozil 600 mg | Part 2: Number of Participants With TEAEs, TESAEs and TEAEMIs | TEAEMIs | 0 Participants |
| Part 1: Camlipixant 50 mg+ Gemfibrozil 600 mg | Part 2: Number of Participants With TEAEs, TESAEs and TEAEMIs | TESAEs | 0 Participants |
Secondary
Part 2: Percentage of AUC0-Infinity Due to Extrapolation From the Time of the Last Observed Concentration to Infinity (%AUC Extrapolation) of Free Dabigatran
Blood samples were collected at indicated time points for PK analysis of Dabigatran. 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, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Population: The PK parameter Population included all participants for whom the Day 1 and Day 10 PK profiles of the dabigatran could be adequately characterized, specifically, when administered alone and in combination with camlipixant (Part 2). Only those participants who were measured and analyzed (i.e., contributed data reported in table) were included in 'Overall Number of Participants Analyzed' field.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Percentage of AUC0-Infinity Due to Extrapolation From the Time of the Last Observed Concentration to Infinity (%AUC Extrapolation) of Free Dabigatran | Day 1 | 2.22 Percentage of AUC extrapolation | Geometric Coefficient of Variation 49.87 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Percentage of AUC0-Infinity Due to Extrapolation From the Time of the Last Observed Concentration to Infinity (%AUC Extrapolation) of Free Dabigatran | Day 10 | 1.95 Percentage of AUC extrapolation | Geometric Coefficient of Variation 52.63 |
Secondary
Part 2: Percentage of AUC0-Infinity Due to Extrapolation From the Time of the Last Observed Concentration to Infinity (%AUC Extrapolation) of Total Dabigatran
Blood samples were collected at indicated time points for PK analysis of Dabigatran. 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, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Population: The PK parameter Population included all participants for whom the Day 1 and Day 10 PK profiles of the dabigatran could be adequately characterized, specifically, when administered alone and in combination with camlipixant (Part 2). Only those participants who were measured and analyzed (i.e., contributed data reported in table) were included in 'Overall Number of Participants Analyzed' field.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Percentage of AUC0-Infinity Due to Extrapolation From the Time of the Last Observed Concentration to Infinity (%AUC Extrapolation) of Total Dabigatran | Day 1 | 1.93 Percentage of AUC extrapolation | Geometric Coefficient of Variation 59.97 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Percentage of AUC0-Infinity Due to Extrapolation From the Time of the Last Observed Concentration to Infinity (%AUC Extrapolation) of Total Dabigatran | Day 10 | 1.58 Percentage of AUC extrapolation | Geometric Coefficient of Variation 37.14 |
Secondary
Part 2: T1/2 Following Administration Free Dabigatran
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Population: The PK parameter Population included all participants for whom the Day 1 and Day 10 PK profiles of the dabigatran could be adequately characterized, specifically, when administered alone and in combination with camlipixant (Part 2). Only those participants who were measured and analyzed (i.e., contributed data reported in table) were included in 'Overall Number of Participants Analyzed' field.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: T1/2 Following Administration Free Dabigatran | Day 1 | 10.49 Hours | Geometric Coefficient of Variation 18.23 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: T1/2 Following Administration Free Dabigatran | Day 10 | 9.18 Hours | Geometric Coefficient of Variation 9.16 |
Secondary
Part 2: T1/2 Following Administration of Total Dabigatran
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Population: The PK parameter Population included all participants for whom the Day 1 and Day 10 PK profiles of the dabigatran could be adequately characterized, specifically, when administered alone and in combination with camlipixant (Part 2). Only those participants who were measured and analyzed (i.e., contributed data reported in table) were included in 'Overall Number of Participants Analyzed' field.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: T1/2 Following Administration of Total Dabigatran | Day 1 | 11.04 Hours | Geometric Coefficient of Variation 30.01 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: T1/2 Following Administration of Total Dabigatran | Day 10 | 10.21 Hours | Geometric Coefficient of Variation 16.9 |
Secondary
Part 2: Tmax of Free Dabigatran
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Population: The PK parameter Population included all participants for whom the Day 1 and Day 10 PK profiles of the dabigatran could be adequately characterized, specifically, when administered alone and in combination with camlipixant (Part 2). Only those participants who were measured and analyzed (i.e., contributed data reported in table) were included in 'Overall Number of Participants Analyzed' field.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Tmax of Free Dabigatran | Day 1 | 2.000 Hours |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Tmax of Free Dabigatran | Day 10 | 2.000 Hours |
Secondary
Part 2: Tmax of Total Dabigatran
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Population: The PK parameter Population included all participants for whom the Day 1 and Day 10 PK profiles of the dabigatran could be adequately characterized, specifically, when administered alone and in combination with camlipixant (Part 2). Only those participants who were measured and analyzed (i.e., contributed data reported in table) were included in 'Overall Number of Participants Analyzed' field.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Tmax of Total Dabigatran | Day 1 | 2.000 Hours |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Tmax of Total Dabigatran | Day 10 | 2.000 Hours |
Secondary
Part 2: Vz/F Free Dabigatran
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Population: The PK parameter Population included all participants for whom the Day 1 and Day 10 PK profiles of the dabigatran could be adequately characterized, specifically, when administered alone and in combination with camlipixant (Part 2). Only those participants who were measured and analyzed (i.e., contributed data reported in table) were included in 'Overall Number of Participants Analyzed' field.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Vz/F Free Dabigatran | Day 1 | 2407.03 Liters | Geometric Coefficient of Variation 54.73 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Vz/F Free Dabigatran | Day 10 | 1883.56 Liters | Geometric Coefficient of Variation 43.72 |
Secondary
Part 2: Vz/F of Total Dabigatran
Blood samples were collected at indicated time points for PK analysis of Dabigatran. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 0.25 , 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, 16, 24, 36, 48, 60, 72 hours post-dose on Day 1 and Day 10
Population: The PK parameter Population included all participants for whom the Day 1 and Day 10 PK profiles of the dabigatran could be adequately characterized, specifically, when administered alone and in combination with camlipixant (Part 2). Only those participants who were measured and analyzed (i.e., contributed data reported in table) were included in 'Overall Number of Participants Analyzed' field.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Vz/F of Total Dabigatran | Day 10 | 1649.21 Liters | Geometric Coefficient of Variation 37.35 |
| Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg | Part 2: Vz/F of Total Dabigatran | Day 1 | 2048.49 Liters | Geometric Coefficient of Variation 61.16 |