Evaluation of the Potential Drug-drug Interactions Between Gemfibrozil or Dabigatran Etexilate and Camlipixant

Phase 1

Completed

Conditions: Cough
Healthy

Interventions: Drug: Camlipixant
Drug: Gemfibrozil
Drug: Dabigatran etexilate

Registration Number: NCT05959447

Lead Sponsor: Bellus Health Inc. - a GSK company

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 45

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg	Camlipixant	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.
Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg	Gemfibrozil	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.
Part 2: Dabigatran etexilate 150 mg + camlipixant 50 mg	Camlipixant	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.
Part 2: Dabigatran etexilate 150 mg + camlipixant 50 mg	Dabigatran etexilate	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.

Primary Outcome Measures

Name	Time	Method
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-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: 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: 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 Outcome Measures

Name	Time	Method
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: 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: 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.
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 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: 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.