Clinical trial NCT05959447: Evaluation of the Potential Drug-drug Interactions Between Gemfibrozil or Dabigatran Etexilate and Camlipixant
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cough
Healthy
Lead sponsor: Bellus Health Inc. - a GSK company
Sponsor class: INDUSTRY
First posted: 2023-07-25
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC-inf) of Camlipixant
timeFrame: 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
measure: Part 1: Area Under the Concentration-time Curve From Time Zero Until the Last Observed Concentration (AUC[0-t]) of Camlipixant
timeFrame: 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
measure: Part 1: Maximal Observed Concentration (Cmax) of Camlipixant
timeFrame: 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
measure: Part 2: AUC(0-Infinity) of Free Dabigatran
timeFrame: 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
measure: Part 2: AUC(0-t) of Free Dabigatran
timeFrame: 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
measure: Part 2: Cmax of Free Dabigatran
timeFrame: 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
measure: Part 2: AUC(0-Infinity) of Total Dabigatran
timeFrame: 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
measure: Part 2: AUC(0-t) of Total Dabigatran
timeFrame: 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
measure: Part 2: Cmax of Total Dabigatran
timeFrame: 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
Secondary outcomes:
measure: Part 1: Time to Reach Maximum Observed Concentration (Tmax) of Camlipixant
timeFrame: 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
measure: Part 1: Terminal Elimination Half-Life (T1/2) Following Administration of Camlipixant
timeFrame: 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
measure: Part 1: Percentage of AUC0-Infinity Due to Extrapolation From the Time of the Last Observed Concentration to Infinity (%AUC Extrapolation) of Camlipixant
timeFrame: 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
measure: Part 1: Terminal Elimination Rate Constant of Camlipixant (Kel)
timeFrame: 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
measure: Part 1: Apparent Clearance (CL/F) of Camlipixant
timeFrame: 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
measure: Part 1: Apparent Volume of Distribution (Vz/F) of Camlipixant
timeFrame: 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
measure: Part 2: Tmax of Free Dabigatran
timeFrame: 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
measure: Part 2: T1/2 Following Administration Free Dabigatran
timeFrame: 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
measure: Part 2: Percentage of AUC0-Infinity Due to Extrapolation From the Time of the Last Observed Concentration to Infinity (%AUC Extrapolation) of Free Dabigatran
timeFrame: 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
measure: Part 2: Kel Free Dabigatran
timeFrame: 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
measure: Part 2: CL/F Free Dabigatran
timeFrame: 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
measure: Part 2: Vz/F Free Dabigatran
timeFrame: 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
measure: Part 2: Tmax of Total Dabigatran
timeFrame: 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
measure: Part 2: T1/2 Following Administration of Total Dabigatran
timeFrame: 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
measure: Part 2: Percentage of AUC0-Infinity Due to Extrapolation From the Time of the Last Observed Concentration to Infinity (%AUC Extrapolation) of Total Dabigatran
timeFrame: 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
measure: Part 2: Kel of Total Dabigatran
timeFrame: 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
measure: Part 2: CL/F of Total Dabigatran
timeFrame: 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
measure: Part 2: Vz/F of Total Dabigatran
timeFrame: 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
measure: 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)
timeFrame: 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]
measure: Part 2: Number of Participants With TEAEs, TESAEs and TEAEMIs
timeFrame: 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]
measure: Part 1: Number of Participants With Abnormal Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) Findings
timeFrame: Day 5, Day 9 pre-dose and 1 hour post-dose, Day 12
measure: Part 2: Number of Participants With Abnormal Clinically Significant Changes in 12-Lead ECG Findings
timeFrame: Day 5, Day 10 and Day 13
measure: Part 1: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP), and Heart Rate
timeFrame: Day 9 and Day 12
measure: Part 2: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: DBP, SBP, and Heart Rate
timeFrame: Day 10 and Day 13
measure: Part 1: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: Respiratory Rate and Oral Temperature
timeFrame: Day 12
measure: Part 2: Number of Participants With Abnormal Clinically Significant Changes in Vital Signs: Respiratory Rate and Oral Temperature
timeFrame: Day 13
measure: Part 1: Number of Participants With Abnormal Clinically Significant Changes During Physical Examination
timeFrame: Up to Day 12
measure: Part 2: Number of Participants With Abnormal Clinically Significant Changes During Physical Examination
timeFrame: Up to Day 13
measure: Part 1: Number of Participants With Abnormal Clinically Significant Changes in Hematology Parameters
timeFrame: Up to Day 12
measure: Part 2: Number of Participants With Abnormal Clinically Significant Changes in Hematology Parameters
timeFrame: Up to Day 13
measure: Part 1: Number of Participants With Abnormal Clinically Significant Changes in Clinical Chemistry Parameters
timeFrame: Up to Day 12
measure: Part 2: Number of Participants With Abnormal Clinically Significant Changes in Clinical Chemistry Parameters
timeFrame: Up to Day 13
measure: Part 1: Number of Participants With Abnormal Clinically Significant Changes in Coagulation Parameters
timeFrame: Up to Day 12
measure: Part 2: Number of Participants With Abnormal Clinically Significant Changes in Coagulation Parameters
timeFrame: Up to Day 13
measure: Part 1: Number of Participants With Abnormal Clinically Significant Changes in Urinalysis
timeFrame: Up to Day 12
measure: Part 2: Number of Participants With Abnormal Clinically Significant Changes in Urinalysis
timeFrame: Up to Day 13
Other outcomes:
Locations:
city: Quebec City
country: Canada
facility: GSK Investigational Site
state: Quebec
Study officials:
References: