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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Biological: MEDI0382
* Drug: Warfarin
* Drug: Esmolol


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI0382<br>All participants will receive MEDI0382. | Biological: MEDI0382<br>* All participants will receive MEDI0382<br>|
| Active Comparator: Warfarin<br>All participants will receive Warfarin | Drug: Warfarin<br>* All participants will receive Warfarin<br>|
| Active Comparator: Esmolol<br>All participants will receive Esmolol | Drug: Esmolol<br>* All participants will receive Esmolol<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 2 Diabetes Mellitus, MEDI0382