A Phase 1, Single- and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MEDI4166 in Subjects With Type 2 Diabetes

A Phase 1, Combined Single- and Multiple-ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of MEDI4166 in Subjects With Type 2 Diabetes Mellitus (T2D)

A Phase 1, combined Single Ascending Dose (SAD) and Multiple-ascending Dose (MAD) study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of MEDI4166 in Subjects with Type 2 Diabetes Mellitus (T2D).

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Biological: MEDI-4166; Biological: Placebo

Detailed Description

This study is a first time in human (FTIH), Phase 1, randomized, double-blind study to evaluate the safety, tolerability, PK, and PD of MEDI4166 administered as both single and multiple ascending doses to subjects with T2D.

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Research Site
  • California
    • Chula Vista, California, United States, 91911
      • Research Site
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Research Site
    • Miami, Florida, United States, 33014
      • Research Site
    • South Miami, Florida, United States, 33143
      • Research Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Research Site
    • Raleigh, North Carolina, United States, 27612
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • Research Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Research Site
  • Texas
    • San Antonio, Texas, United States, 78229
      • Research Site
    • San Antonio, Texas, United States, 78209
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 2 Diabetes, ages 18-65
• Must provide written informed consent
• BMI>=25 and =<42
• Venous access suitable for multiple cannulations
• Vital signs within normal specified ranges
• Females must be non-lactating and non-childbearing potential
• Males must practice 2 effective contraceptive measures if sexually active

Exclusion Criteria:

• Any concurrent condition that in the opinion of the investigator would interfere with the evaluation of the investigational product
• History or presence of gastrointestinal, renal, or hepatic disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
• History of cancer, with the exception of basal cell carcinoma or carcinoma of the cervix
• Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks prior to dosing
• Positive Hepatitis B, Hepatitis C or HIV test or use of antiretroviral medications at screening
• Current or previous use of systemic corticosteroids within the past 28 days prior to screening
• Use of any medicinal products or herbal preparations licensed for weight loss is prohibited.
• Positive drug screen
• Type 1 diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo administered subcutaneously	Biological: Placebo; Placebo administered subcutaneously
Experimental: MEDI-4166; MEDI-4166 administered subcutaneously	Biological: MEDI-4166; MEDI-4166 administered subcutaneously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166	Treatment emergent adverse events (TEAEs) and serious adverse events (TESAEs)	43 days post dosing
Part A: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166	12 lead electrocardiogram including RR, PR, QRS, QT and QTc intervals	43 days post dosing
Part A: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166	Vital signs (systolic and diastolic blood pressure, pulse rate, temperature, and respiratory rate)	43 days post dosing
Part A: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166	Clinical laboratory assessments (serum chemistry, hematology, urinalysis)	43 days post dosing
Part A: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166	Physical examination	43 days post dosing
Part B: Change in glucose AUC measured up to 240 minutes after mixed meal tolerance test (MMTT) from baseline to Day 36	Part B: Change in glucose AUC measured up to 240 minutes after mixed meal tolerance test (MMTT) from baseline to Day 36	36 days post dosing
Part B: Change in LDL-C from baseline to Day 36	Part B: Change in LDL-C from baseline to Day 36	36 days post dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Pharmacokinetics of MEDI4166, maximum plasma concentration (Cmax)	Part A: Pharmacokinetics of MEDI4166, maximum plasma concentration (Cmax)	43 days post dosing
Part A: Pharmacokinetics of MEDI4166, area under the curve concentration (AUC)	Part A: Pharmacokinetics of MEDI4166, area under the curve concentration (AUC)	43 days post dosing
Part A: Change from baseline in LDL-C	Part A: Change from baseline in LDL-C	43 days post dosing
Part A: Proportion of subjects with Anti-drug Antibodies (ADA) to MEDI4166	Part A: Proportion of subjects with ADA to MEDI4166	43 days post dosing
Part B: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166	Treatment emergent adverse events (TEAEs) and serious adverse events (TESAEs)	71 days post dosing
Part B: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166	12 lead electrocardiogram including RR, PR, QRS, QT and QTc intervals	71 days post dosing
Part B: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166	Vital signs (systolic and diastolic blood pressure, pulse rate, temperature, and respiratory rate)	71 days post dosing
Part B: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166	Clinical laboratory assessments (serum chemistry, hematology, urinalysis)	71 days post dosing
Part B: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166	Physical examination	71 days post dosing
Part B: Pharmacokinetics of MEDI4166, maximum plasma concentration (Cmax)	Part B: Pharmacokinetics of MEDI4166, maximum plasma concentration (Cmax)	71 days post dosing
Part B: Pharmacokinetics of MEDI4166, area under the curve concentration (AUC)	Part B: Pharmacokinetics of MEDI4166, area under the curve concentration (AUC)	71 days post dosing
Part B: Change from baseline in fructosamine levels	Part B: Change from baseline in fructosamine levels	36 days post dosing
Part B: Proportion of subjects with ADA to MEDI4166	Part B: Proportion of subjects with ADA to MEDI4166	71 days post dosing
Part A: Pharmacokinetics of MEDI4166, time to maximum observed plasma drug concentration (Tmax)	Part A: Pharmacokinetics of MEDI4166, time to maximum observed plasma drug concentration (Tmax)	43 days post dosing
Part A: Change from baseline in glucose AUC up to 240 minutes	Part A: Change from baseline in glucose AUC up to 240 minutes	43 days post dosing
Part B: Pharmacokinetics of MEDI4166, time to maximum observed plasma drug concentration (Tmax)	Part B: Pharmacokinetics of MEDI4166, time to maximum observed plasma drug concentration (Tmax)	71 days post dosing

Collaborators and Investigators

• Sponsor: MedImmune LLC

Publications and helpful links

General Publications

• Jain M, Carlson G, Cook W, Morrow L, Petrone M, White NE, Wang T, Naylor J, Ambery P, Lee C, Hirshberg B. Randomised, phase 1, dose-finding study of MEDI4166, a PCSK9 antibody and GLP-1 analogue fusion molecule, in overweight or obese patients with type 2 diabetes mellitus. Diabetologia. 2019 Mar;62(3):373-386. doi: 10.1007/s00125-018-4789-6. Epub 2018 Dec 28.

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2015
• Primary Completion (Actual): April 14, 2017
• Study Completion (Actual): April 14, 2017

Study Registration Dates

• First Submitted: August 13, 2015
• First Submitted That Met QC Criteria: August 13, 2015
• First Posted (Estimate): August 17, 2015

Study Record Updates

• Last Update Posted (Actual): March 13, 2019
• Last Update Submitted That Met QC Criteria: March 12, 2019
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: MEDI-4166, diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: D6240C00001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No