Healthy Volunteers
Conditions
Keywords
type 2 Diabetes Mellitus, MEDI0382
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.
Interventions
BIOLOGICALMEDI0382
All participants will receive MEDI0382
DRUGWarfarin
All participants will receive Warfarin
DRUGEsmolol
All participants will receive Esmolol
Sponsors
MedImmune LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum international normalized ratio (INRmax) | Days 2-8 and Days 27-33 | To assess the INR max 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Number of patients with Adverse Events (AEs) | 33 Days | To assess the adverse events as a criteria of safety and tolerability variables. |
| 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. |
| 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. |
| Clinical laboratory assessments (hematology) | Days 1 and 33 | To assess hematology 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 |
| 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 |
| 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 assessment (urinalysis) | Day -1 | To assess urinalysis as a criteria of safety and tolerability variables. |
Countries
United States
Outcome results
None listed