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CompletedNCT03341013Updated Feb 14, 2018

A Pilot Study Investigating Bioequivalence Between a Single Dose of Formulation 2 and Formulation 3 of MEDI0382

A Phase 1 interventional study of MEDI0382 Formulation 2 and MEDI0382 Formulation 3 in Type 2 Diabetes Mellitus, sponsored by MedImmune LLC. Completed at 1 site in United States. Open to participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-02-14.

Sponsored by MedImmune LLC · Phase 1, Interventional, and Other

Phase
Phase 1
Study type
Interventional
Enrollment
24
Allocation
Randomized
Ages
18 Years to 45 Years
Sex
All
01

Study summary

This is a randomized, open label, cross-over, two-period, pilot study in healthy adult subjects to evaluate the bioequivalence between formulation 2 and formulation 3 of MEDI0382 after a single subcutaneous (SC) dose. The study will be conducted at a single US center. Each subject will be randomized to receive a single 100 μg (or equimolar equivalent) SC dose of both formulation 2 and 3 of MEDI0382 on two different in-house periods separated by a washout period of 7 days. Formulation 3 of MEDI0382 has not been administered to humans previously. Blood samples for PK analyses of MEDI0382 concentrations will be taken predose and at 11 time points up to 48 hours after dosing (Days 3 and 12). Bedside plasma glucose levels will be monitored before meals and at bedtime during Days 1 and 10 and will be measured prior to breakfast on Days 2 and 11.

Read the detailed description

This is a randomized, open label, cross-over, two-period, pilot study in healthy adult subjects to evaluate the bioequivalence between formulation 2 and formulation 3 of MEDI0382 after a single subcutaneous (SC) dose. The study will be conducted at a single US center. Each subject will be randomized to receive a single 100 μg (or equimolar equivalent) SC dose of both formulation 2 and 3 of MEDI0382 on two different in-house periods separated by a washout period of 7 days. Formulation 3 of MEDI0382 has not been administered to humans previously.

Subjects will receive the same absolute amount of MEDI0382, when dosed with either formulation 2 or formulation 3. Formulations of MEDI0382 will be administered via SC injection in the abdomen of subjects. Subjects will be in the study for a maximum of 59 days, which includes a screening period of up to 21 days. On Day 1, subjects will admitted to the clinic and will be randomized to receive formulation 2 and formulation 3 in one of two sequences; subjects randomized to sequence 1 will receive formulation 2 on Day 1 and formulation 3 on Day 10 and subjects randomized to sequence 2 will receive formulation 3 on Day 1 and formulation 2 on Day 10.

On Day 3, subjects will be discharged from the clinic and a 7-day washout period will follow. Subjects will return to the clinic on Day 10 to receive the second dose of investigational product and will remain in-house for 3 days. After discharge on Day 12, subjects will return on Day 38 for the end of study visit. Blood samples for PK analyses of MEDI0382 concentrations will be taken predose and at 11 time points up to 48 hours after dosing (Days 3 and 12). Bedside plasma glucose levels will be monitored before meals and at bedtime during Days 1 and 10 and will be measured prior to breakfast on Days 2 and 11.

02

Conditions studied

  • Type 2 Diabetes Mellitus

Keywords

  • Type 2 Diabetes Mellitus
  • GLP-1 receptor agonists
03

Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  1. Healthy subjects age 18 through 45 years at the time of screening.
  2. Provision of signed and dated written informed consent prior to study-specific procedures.
  3. Body mass index between 19 and 30 kg/m2 (inclusive) at screening
  4. Good general health as judged by the investigator, based on medical history, physical examination including 12-lead ECG, vital signs, and blood and urinary laboratory assessments.
  5. Female subjects of childbearing potential must have a negative pregnancy test at screening and randomization and must not be lactating.
  6. Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception (see Section 10.2 for definition of females of childbearing potential and for a description of highly effective methods of contraception) from screening and must agree to continue using such precautions through to the end of the study. It is strongly recommended for the male partner of a female subject to also use a male condom plus spermicide throughout this period. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.

Exclusion criteria

Exclusion Criteria:

  1. History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product, put the subject at risk, influence the subject's ability to participate, or affect the interpretation of the results of the study
  2. Impaired renal function, defined as s-creatinine ≥ 130 µmol/L
  3. Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m2
  4. Blood pressure and heart rate in supine position outside the ranges of 90-140 mmHg systolic, 50-90 mmHg diastolic and heart rate 40-100 beats/min following a 10-minute rest period.
  5. Any clinically significant abnormal ECG, as judged by the investigator
  6. Active hepatitis B, measured by positive tests of surface antigen HBsAg and/or active hepatitis C, measured by positive hepatitis C virus antibody tests
  7. Positive human immunodeficiency virus antibodies
  8. Known or suspected allergy to MEDI0382, any component of the formulation, or related products
  9. Use of any prescription or nonprescription medication, except for paracetamol, hormonal contraceptives, and vitamins within the last 72 hours prior to check-in
  10. History of alcoholism or drug abuse during the last 12 months
  11. Smoking of cigarettes or other tobacco products
  12. Habitual excessive consumption of methylxanthine-containing (theophylline, caffeine or theobromine) beverages and foods (coffee, tea, soft drinks such as red bull, cola, chocolate) as judged by the investigator
  13. Blood donation within the last 3 months
  14. Participation in any other trial investigating other products or involving blood sampling within the past 30 days
  15. Potentially noncompliant or uncooperative, as judged by the investigator
  16. Substance dependence likely to impact subject safety or compliance with study procedures
  17. Psychiatric illness such that subjects have been committed to an institution by way of official or judicial order
  18. Involvement of any AstraZeneca, MedImmune, the contract research organization, or the study site employee or their close relatives
04

Study design

Phase
Phase 1
Primary purpose
Other
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
24 participants (actual)

Study arms

  • Experimental
    Sequence 1

    formulation 2 on Day 1 and formulation 3 on Day 10

    Drug: MEDI0382 Formulation 2 · Drug: MEDI0382 Formulation 3

  • Experimental
    Sequence 2

    formulation 3 on Day 1 and formulation 2 on Day 10

    Drug: MEDI0382 Formulation 2 · Drug: MEDI0382 Formulation 3

Interventions

  • DrugMEDI0382 Formulation 2

    Sequence 1 Period 1 and Sequence 2 Period 2.

  • DrugMEDI0382 Formulation 3

    Sequence 1 Period 2 and Sequence 2 Period 1

05

What researchers measure

Primary outcomes

  1. Area under the drug concentration curve

    To evaluate bioequivalence between formulation 2 and formulation 3 of MEDI0382

    Time frame: 48 hours

  2. Maximum observed plasma concentration of MEDI0382

    To evaluate bioequivalence between formulation 2 and formulation 3 of MEDI0382.

    Time frame: 48 hours

Secondary outcomes

  1. Area under the plasma drug concentration versus time curve from zero to infinity and to last observation

    To compare the pharmacokinetic (PK) profiles of MEDI0382 formulation 2 versus formulation 3.

    Time frame: 48 hours

  2. Time to maximum observed plasma drug concentration

    To compare the pharmacokinetic (PK) profiles of MEDI0382 formulation 2 versus formulation 3.

    Time frame: 48 hours

  3. Terminal phase elimination half-life

    To compare the pharmacokinetic (PK) profiles of MEDI0382 formulation 2 versus formulation 3.

    Time frame: 48 hours

  4. Apparent clearance

    To compare the pharmacokinetic (PK) profiles of MEDI0382 formulation 2 versus formulation 3.

    Time frame: 48 hours

  5. Adverse Events

    To evaluate the safety and tolerability of a single dose of MEDI0382 in formulation 2 and 3.

    Time frame: 38 days

  6. 12 lead electrocardiogram including RR, PR, QRS, QT, and QTc intervals

    To evaluate the safety and tolerability of a single dose of MEDI0382 in formulation 2 and 3.

    Time frame: 38 days

  7. Anti-drug antibody titer

    To evaluate the immunogenicity of a single dose of MEDI0382 in formulation 2 and 3.

    Time frame: 38 days

  8. Vital signs (temperature)

    To evaluate the safety and tolerability of a single dose of MEDI0382 in formulation 2 and 3

    Time frame: 38 days

  9. Anti-drug antibody incidence

    To evaluate the immunogenicity of a single dose of MEDI0382 in formulation 2 and 3.

    Time frame: 38 days

  10. Clinical laboratory assessments (hematology)

    To evaluate the safety and tolerability of a single dose of MEDI0382 in formulation 2 and 3

    Time frame: 38 days

  11. Vital signs (systolic and diastolic blood pressure)

    To evaluate the safety and tolerability of a single dose of MEDI0382 in formulation 2 and 3.

    Time frame: 38 days

  12. Vital signs (pulse rate and respiratory rate)

    To evaluate the safety and tolerability of a single dose of MEDI0382 in formulation 2 and 3

    Time frame: 38 days

  13. Clinical laboratory assessments (serum chemistry)

    To evaluate the safety and tolerability of a single dose of MEDI0382 in formulation 2 and 3

    Time frame: 38 days

  14. Clinical laboratory assessments (urinalysis)

    To evaluate the safety and tolerability of a single dose of MEDI0382 in formulation 2 and 3

    Time frame: 38 days

06

Study locations

1 site
  • Research Site
    Dallas, Texas 75247, United States
07

Registry details

Key details

Study ID
NCT03341013
Lead sponsor
MedImmune LLC
Responsible party
Sponsor
First posted
Nov 14, 2017
Start date
Nov 30, 2017
Primary completion
Jan 29, 2018
Completion
Jan 29, 2018
Last update
Feb 14, 2018

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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