Clinical trial NCT03347968: Study to Compare Pharmacokinetics & Pharmacodynamics of Warfarin & Esmolol in the Absence & Presence of MEDI0382
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: type 2 Diabetes Mellitus, MEDI0382
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2017-11-20
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum international normalized ratio (INRmax)
timeFrame: Days 2-8 and Days 27-33
measure: Change in heart rate from resting after a 9-minute excercise treadmill test (Bruce Protocol, first 3 stages)
timeFrame: Days 1 and 26
measure: Maximum international normalized ratio (INRmax)
timeFrame: Days 2-8 and Days 27-33
Secondary outcomes:
measure: PK(AUC) of R-Warfarin and S-Warfarin
timeFrame: Days 2 and 27
measure: PK (Cmax) of R-Warfarin and S-Warfarin
timeFrame: Days 2 and 27
measure: Number of patients with Adverse Events (AEs)
timeFrame: 33 Days
measure: 12 lead electrocardiogram including RR, PR, QRS, QT and QTc intervals
timeFrame: Day 1, Day 8, Day 13, and Day 18
measure: Anti-drug antibody titer incidence
timeFrame: Days 1 and 33
measure: Clinical laboratory assessments (hematology)
timeFrame: Days 1 and 33
measure: Vital signs (systolic and diastolic blood pressure)
timeFrame: Days 1-8, Days 12 and 13, Days 25-33
measure: Vital signs (pulse rate and respiratory rate
timeFrame: Days 1-8, Days 12 and 13, Days 25-33
measure: Clinical laboratory assessments (serum chemistry)
timeFrame: Day -1, Day 8, Day 17, Day 25 and Day 33
measure: Clinical laboratory assessment (urinalysis)
timeFrame: Day -1
Other outcomes:
Locations:
city: Daytona Beach
country: United States
facility: Research Site
state: Florida
Study officials:
affiliation: MedImmune LLC
name: Armando Flor
role: STUDY_DIRECTOR
References: