Study to Compare Pharmacokinetics & Pharmacodynamics of Warfarin & Esmolol in the Absence & Presence of MEDI0382

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Biological: MEDI0382; Drug: Warfarin; Drug: Esmolol

• Registration Number: NCT03347968
• Lead Sponsor: MedImmune LLC

Brief Summary

A Phase 1 study to evaluate the effect of MEDI0382 on PK and PD of warfarin and esmolol in healthy subjects.

Detailed Description

This is a Phase 1 open label, one-sequence, crossover study to evaluate the effect of MEDI0382 on PK and PD of warfarin and esmolol in healthy subjects. The safety and tolerability of MEDI0382 in combination with warfarin and esmolol will also be evaluated. Following screening, the study consists of 2 5-day inpatient stays followed by outpatient visits.

Study Timeline

• Study First Submitted: 2017-10-16
• Study First Submitted QC: 2017-11-17
• Study First Posted: 2017-11-20
• Study Start: 2017-11-27
• Status Verified: 2018-04
• Primary Completion: 2018-04-09
• Study Completion: 2018-04-09
• Last Update Submitted: 2018-04-24
• Last Update Posted: 2018-04-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

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• Healthy volunteers aged ≥ 18 to 45 years
• BMI between 18 -30 kg/m2
• Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception

Exclusion Criteria

• Any concurrent condition that in the opinion of the investigator would interfere with the evaluation of the investigational product
• Receipt of investigational product as part of a clinical study or a GLP-1 analogue containing preparation within the last 30 days or 5 half-lives of the drug (whichever is longer) at the time of screening.
• Concurrent participation in another study of any kind
• Severe allergy/hypersensitivity to any of the proposed study treatments or excipients.
• History or presence of gastrointestinal (GI), hepatic, or renal disease or any other conditions known to interfere with absorption, distribution, metabolism or excretion of drugs.
• Impaired renal function is defined as estimated glomerular filtration rate (eGFR) < 60 mL/minute/1.73 m2 at screening.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of screening.
• History of hemophilia, von Willebrand's disease, lupus anticoagulant, or other diseases/syndromes that can either alter or increase the propensity for bleeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
MEDI0382	MEDI0382	All participants will receive MEDI0382.
Warfarin	Warfarin	All participants will receive Warfarin
Esmolol	Esmolol	All participants will receive Esmolol

Primary Outcome Measures

Name	Time	Method
Maximum international normalized ratio (INRmax)	Days 2-8 and Days 27-33	To assess the AUC INR in the absence and presence of Warfarin on a steady state MEDI0382
Change in heart rate from resting after a 9-minute excercise treadmill test (Bruce Protocol, first 3 stages)	Days 1 and 26	To assess the effects of MEDI0382 on the hear rate-lowering effect of esmolol during treadmill test.

Secondary Outcome Measures

Name	Time	Method
PK(AUC) of R-Warfarin and S-Warfarin	Days 2 and 27	To assess AUC of R-warfarin and S-warfarin in the presence and absence of steady state MEDI0382
12 lead electrocardiogram including RR, PR, QRS, QT and QTc intervals	Day 1, Day 8, Day 13, and Day 18	To assess the cardiovascular system functioning as a criteria of safety and tolerability variables.
Vital signs (systolic and diastolic blood pressure)	Days 1-8, Days 12 and 13, Days 25-33	To assess the vital signs as a criteria of safety and tolerability variables
Clinical laboratory assessments (serum chemistry)	Day -1, Day 8, Day 17, Day 25 and Day 33	To assess clinical chemistry as a criteria of safety and tolerability variables.
PK (Cmax) of R-Warfarin and S-Warfarin	Days 2 and 27	To assess Cmax of R-warfarin and S-warfarin in the presence and absence of steady state MEDI0382
Anti-drug antibody titer incidence	Days 1 and 33	To evaluate the safety and tolerability of multiple doses of MEDI0382 in conjunction with Warfarin and Esmolol.
Clinical laboratory assessments (hematology)	Days 1 and 33	To assess hematology as a criteria of safety and tolerability variables..
Clinical laboratory assessment (urinalysis)	Day -1	To assess urinalysis as a criteria of safety and tolerability variables.
Number of patients with Adverse Events (AEs)	33 Days	To assess the adverse events as a criteria of safety and tolerability variables.
Vital signs (pulse rate and respiratory rate	Days 1-8, Days 12 and 13, Days 25-33	To assess the vital signs as a criteria of safety and tolerability variables

Trial Locations

Locations (1)

Research Site; 🇺🇸 Daytona Beach, Florida, United States