Phase 1
Completed N=17
A Study of Milvexian Using an IV Microtracer With Additional Formulation and Food Effect Comparison in Healthy Participants
Healthy Volunteers
Source: ClinicalTrials.gov NCT04965389 ↗
Enrolled (actual)
17
Serious AEs
0.0%
Results posted
Aug 2023
Primary outcomePrimary: Absolute Bioavailability (F) — 105; 54.2; 44.3; 58.2 Percentage of drug
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Absolute Bioavailability (F) |
105; 54.2; 44.3; 58.2; 75.6 | — |
| SECONDARY Number of Participants Experiencing Adverse Events (AEs) |
8; 2; 2; 0; 2; 0 | — |
| SECONDARY Number of Participants Experiencing Serious Adverse Events (SAE) |
0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants Experiencing Abnormal Vital Sign Measurements |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Abnormal Electrocardiograms (ECGs) |
2; 2; 1; 0; 1 | — |
| SECONDARY Number of Participants With Abnormal Physical Examinations |
0; 2; 0; 1; 0 | — |
| SECONDARY Number of Participants With Clinical Laboratory Test Abnormalities |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) |
2929; 1200; 130; 185; 1696 | — |
| SECONDARY Time of Maximum Observed Plasma Concentration (Tmax) |
1.27; 4.00; 4.00; 4.00; 5.00 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-T)] |
30844; 15855; 1603; 2183; 21972 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity [AUC(INF)] |
31435; 16464; 1569; 2061; 22496 | — |
| SECONDARY Apparent Clearance of Drug After Extravascular Administration (CLT/F) |
6.36; 12.1; 15.9; 12.1; 8.89 | — |
| SECONDARY Renal Clearance (CLR) |
1.63; 1.68; 1.91; 1.84; 1.70 | — |
| SECONDARY Apparent Volume of Distribution at Terminal Phase After Extravascular Administration (Vz/F) |
121; 243; 344; 245; 159 | — |
| SECONDARY Total Amount of Unchanged Drug Excreted Into the Urine (Ae) |
50.2; 26.7; 3.06; 4.01; 37.3 | — |
| SECONDARY Total Percent Urinary Recovery (%UR) |
25.1; 13.3; 12.2; 16.0; 18.6 | — |
| SECONDARY Half-life (T-HALF) |
13.3; 14.3; 15.8; 14.5; 12.8 | — |
| SECONDARY Mean Residence Time (MRT) Following an IV Dose in Treatment A |
14.8 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) Following an IV Dose in Treatment A |
99.1 | — |
| SECONDARY Relative Bioavailability (Frel) Based on Ratios of Cmax |
NA; 0.403; 0.358; 0.510; 0.574 | — |
| SECONDARY Relative Bioavailability (Frel) Based on Ratios of AUC(0-T) and AUC(INF) |
NA; 0.513; 0.425; 0.570; 0.716; NA | — |
| SECONDARY Food Effect Based on Ratios of Cmax Following an SDD Capsule Dose in Treatment B, C, D, and E |
1197; 128; 185; 1709 | — |
| SECONDARY Food Effect Based on Ratios of AUC(0-T) and AUC(INF) Following an SDD Capsule Dose in Treatment B, C, D, and E |
15871; 1592; 2170; 22171; 16480; 1545 | — |
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
Data sourced from ClinicalTrials.gov (NCT04965389). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.