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

A Phase 1, Open-label Study to Compare the Pharmacokinetics and Pharmacodynamics of Warfarin and Esmolol in the Absence and Presence of MEDI0382 in Healthy Subjects

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Biological: MEDI0382; Drug: Warfarin; Drug: Esmolol

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 Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:.

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MEDI0382; All participants will receive MEDI0382.	Biological: MEDI0382; All participants will receive MEDI0382
Active Comparator: Warfarin; All participants will receive Warfarin	Drug: Warfarin; All participants will receive Warfarin
Active Comparator: Esmolol; All participants will receive Esmolol	Drug: Esmolol; All participants will receive Esmolol

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Investigators: Study Director: Armando Flor, MedImmune LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2017
• Primary Completion (Actual): April 9, 2018
• Study Completion (Actual): April 9, 2018

Study Registration Dates

• First Submitted: October 16, 2017
• First Submitted That Met QC Criteria: November 17, 2017
• First Posted (Actual): November 20, 2017

Study Record Updates

• Last Update Posted (Actual): April 25, 2018
• Last Update Submitted That Met QC Criteria: April 24, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: type 2 Diabetes Mellitus, MEDI0382
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anticoagulants; Adrenergic beta-1 Receptor Antagonists; Warfarin; Esmolol
• Other Study ID Numbers: D5670C00009

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No