Clinical trial NCT04965389: A Study of Milvexian Using an IV Microtracer With Additional Formulation and Food Effect Comparison in Healthy Participants
Official title: A Study to Assess the Absolute Oral Bioavailability of Milvexian Using a 14C-Microtracer and Oral Solution in Healthy Participants With Additional Food Effect Comparison of a Spray-Dried Dispersion Formulation of Milvexian in Capsules
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Bioavailability
BMS-986177
14C-Microtracer
Milvexian
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2021-07-16
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the absolute oral bioavailability (amount of drug entering the bloodstream) of spray-dried dispersion (SDD) milvexian capsules in the fed and fasted states, and to bridge the exposures seen using only the oral solution.


Eligibility criteria: Inclusion Criteria:

* Healthy, as determined by no clinically significant deviation from normal in medical history, physical examination, electrocardiograms (ECGs), and clinical laboratory determinations
* Body mass index (BMI) of 18.0 to 32.0 kg/m², inclusive. BMI = weight (kg)/ (height \[m\])²

Exclusion Criteria:

* History of gastrointestinal (GI) disease, upper or lower GI bleeding within 6 months, intracranial bleeding, tumor, aneurysms
* History or evidence of abnormal bleeding or coagulation disorder and/or evidence of coagulopathy, prolonged or unexplained clinically significant bleeding, or frequent unexplained bruising or thrombus formation, or a history of spontaneous bleeding, such as epistaxis, or family history of coagulopathies
* Any acute or chronic medical illness considered clinically significant by the investigator
* History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory, neurological or psychiatric disorder, as judged by the investigator

Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Absolute Bioavailability (F)
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
Secondary outcomes:
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 11 weeks)
measure: Number of Participants Experiencing Serious Adverse Events (SAE)
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 11 weeks)
measure: Number of Participants Experiencing Abnormal Vital Sign Measurements
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
measure: Number of Participants With Abnormal Electrocardiograms (ECGs)
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
measure: Number of Participants With Abnormal Physical Examinations
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
measure: Number of Participants With Clinical Laboratory Test Abnormalities
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
measure: Time of Maximum Observed Plasma Concentration (Tmax)
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-T)]
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
measure: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity [AUC(INF)]
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
measure: Apparent Clearance of Drug After Extravascular Administration (CLT/F)
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
measure: Renal Clearance (CLR)
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
measure: Apparent Volume of Distribution at Terminal Phase After Extravascular Administration (Vz/F)
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
measure: Total Amount of Unchanged Drug Excreted Into the Urine (Ae)
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
measure: Total Percent Urinary Recovery (%UR)
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
measure: Half-life (T-HALF)
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
measure: Mean Residence Time (MRT) Following an IV Dose in Treatment A
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
measure: Volume of Distribution at Steady State (Vss) Following an IV Dose in Treatment A
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
measure: Relative Bioavailability (Frel) Based on Ratios of Cmax
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
measure: Relative Bioavailability (Frel) Based on Ratios of AUC(0-T) and AUC(INF)
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
measure: Food Effect Based on Ratios of Cmax Following an SDD Capsule Dose in Treatment B, C, D, and E
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
measure: Food Effect Based on Ratios of AUC(0-T) and AUC(INF) Following an SDD Capsule Dose in Treatment B, C, D, and E
timeFrame: Day 1 of Treatment Periods 1-5 (up to approximately 7 weeks)
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: