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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03347968
• Other study ID #: D5670C00009
• Status: Completed
• Phase: Phase 1
• First received: October 16, 2017
• Last updated: April 24, 2018
• Start date: November 27, 2017
• Est. completion date: April 9, 2018

Study information

• Verified date: April 2018
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: April 9, 2018
• Est. primary completion date: April 9, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Biological:
• MEDI0382
All participants will receive MEDI0382

Drug:
• Warfarin
All participants will receive Warfarin
• Esmolol
All participants will receive Esmolol

Locations

Country	Name	City	State
United States	Research Site	Daytona Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	Number of patients with Adverse Events (AEs)	To assess the adverse events as a criteria of safety and tolerability variables.	33 Days
Secondary	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
Secondary	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
Secondary	Clinical laboratory assessments (hematology)	To assess hematology as a criteria of safety and tolerability variables..	Days 1 and 33
Secondary	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
Secondary	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
Secondary	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
Secondary	Clinical laboratory assessment (urinalysis)	To assess urinalysis as a criteria of safety and tolerability variables.	Day -1