Clinical trial NCT03235050: A Study to Evaluate the Efficacy and Safety of MEDI0382 in the Treatment of Overweight and Obese Subjects With Type 2 Diabetes
Official title: A Phase IIb, Randomised, Parallel, Double-Blind Placebo-Controlled and Open-Label Active Comparator Study to Evaluate the Efficacy and Safety of MEDI0382 in the Treatment of Overweight and Obese Subjects With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: MedImmune LLC
First posted: 2017-08-01
Enrollment: 834
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised, parallel, double-blind, placebo-controlled study with an open-label active comparator.
Primary purpose: TREATMENT

Brief summary: This study is designed to evaluate the dose range for MEDI0382 with respect to blood glucose control and weight loss effects, as well as to further explore the safety profile of MEDI0382


Eligibility criteria: Inclusion Criteria:

* Provision of informed consent
* Male and female subjects aged ≥ 18 years at screening
* Body mass index ≥ 25 kg/m2 at screening
* HbA1c range of 7.0% to 10.5% (inclusive) at screening
* Diagnosed with type-2 diabetes mellitus (T2DM) and treated with metformin (stable dose of ≥1500 mg/day or maximal tolerated dose) for at least 2 months prior to screening. Use of another glucose-lowering medication for up to 2 weeks in the 2 months prior to screening is acceptable
* Women of childbearing potential (WOCBP), not breastfeeding and using appropriate birth control to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of investigational product (IP), with a negative pregnancy test within 72 hours prior to the start of IP

Exclusion Criteria:

* History of, or any existing condition that, in the opinion of the Investigator, would interfere with evaluation of the IP, put the subject at risk, influence the subject's ability to participate or affect the interpretation of the results of the study and/or any subject unable or unwilling to follow study procedures
* Any subject who has received another IP as part of a clinical study or a GLP-1 receptor agonist containing preparation within the last 30 days or 5 half lives of the drug (whichever is longer) at the time of screening
* Severe allergy/hypersensitivity to any of the proposed study treatments or excipients
* Symptoms of acutely decompensated blood glucose control, a history of type 1 diabetes mellitus or diabetic ketoacidosis, or if the subject has been treated with daily subcutaneous (SC) insulin for a period longer than 2 weeks within 90 days prior to screening
* Acute or chronic pancreatitis. Subjects with serum triglyceride concentrations above 1000 mg/dL (11 mmol/L) at screening
* Significant inflammatory bowel disease or other severe disease or surgery affecting the upper Gastrointestinal (GI) tract
* Significant hepatic disease
* Impaired renal function defined as estimated glomerular filtration rate (eGFR) ≤30 mL/minute/1.73m2 at screening
* Severely uncontrolled hypertension
* Unstable angina pectoris, myocardial infarction (MI), transient ischaemic attack (TIA), or stroke within 3 months prior to screening
* Severe congestive heart failure

Primary outcomes:
measure: Change in HbA1c
timeFrame: From baseline to 14 weeks
measure: Percent Change in Body Weight
timeFrame: From baseline to 14 weeks
Secondary outcomes:
measure: Change in HbA1c
timeFrame: from baseline to 26 weeks and 54 weeks
measure: Percentage of Participants Achieving an HbA1c Target < 7.0%
timeFrame: after 14, 26, and 54 weeks
measure: Percent Change in Body Weight
timeFrame: from baseline to 26 weeks and 54 weeks
measure: Absolute Change in Body Weight
timeFrame: from baseline to 14 weeks, 26 weeks and 54 weeks
measure: Percent Change in Body Weight Versus Active Comparator
timeFrame: from baseline to 14 weeks, 26 weeks and 54 weeks
measure: Absolute Change in Body Weight Versus Active Comparator
timeFrame: from baseline to 14 weeks, 26 weeks and 54 weeks
measure: Percentage of Participants Achieving Weight Loss of ≥5% and ≥10%
timeFrame: after 14 weeks, 26 weeks and 54 weeks
measure: Percentage of Participants Rescued or Discontinued for Lack of Glycaemic Control
timeFrame: at 14 weeks, 26 weeks and 54 weeks
measure: Pharmacokinetic (PK) Endpoint: Trough Plasma Concentration (Cmin)
timeFrame: Time points at which outcome measure were assessed for plasma concentration were Weeks 1,2,6,10,14,18,22,26, and 54
measure: Immunogenicity Endpoint: Overall Antidrug Antibody (ADA) Incidence (Number and Percentage of Positive Partipants)
timeFrame: Baseline through 54-week treatment period and 28-day follow-up
measure: Immunogenicity Endpoint: Median Titer of the Anti-Drug Antibodies (ADA) to MEDI0382 in the Positive Participants
timeFrame: Baseline through 54-week treatment period and 28-day follow-up
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Chandler
country: United States
facility: Research Site
state: Arizona
city: Glendale
country: United States
facility: Research Site
state: Arizona
city: Glendale
country: United States
facility: Research Site
state: Arizona
city: Mesa
country: United States
facility: Research Site
state: Arizona
city: Marietta
country: United States
facility: Research Site
state: Georgia
city: Evansville
country: United States
facility: Research Site
state: Indiana
city: Baton Rouge
country: United States
facility: Research Site
state: Louisiana
city: Metairie
country: United States
facility: Research Site
state: Louisiana
city: Elkridge
country: United States
facility: Research Site
state: Maryland
city: Bridgeton
country: United States
facility: Research Site
state: Missouri
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Brooklyn
country: United States
facility: Research Site
state: New York
city: Morehead City
country: United States
facility: Research Site
state: North Carolina
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Greer
country: United States
facility: Research Site
state: South Carolina
city: Houston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Plano
country: United States
facility: Research Site
state: Texas
city: Layton
country: United States
facility: Research Site
state: Utah
city: Arlington
country: United States
facility: Research Site
state: Virginia
city: Manassas
country: United States
facility: Research Site
state: Virginia
city: Botevgrad
country: Bulgaria
facility: Research Site
city: Kozloduy
country: Bulgaria
facility: Research Site
city: Kyustendil
country: Bulgaria
facility: Research Site
city: Lukovit
country: Bulgaria
facility: Research Site
city: Petrich
country: Bulgaria
facility: Research Site
city: Pleven
country: Bulgaria
facility: Research Site
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Russe
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Stara Zagora
country: Bulgaria
facility: Research Site
city: Red Deer
country: Canada
facility: Research Site
state: Alberta
city: Sherwood Park
country: Canada
facility: Research Site
state: Alberta
city: Burlington
country: Canada
facility: Research Site
state: Ontario
city: Etobicoke
country: Canada
facility: Research Site
state: Ontario
city: Guelph
country: Canada
facility: Research Site
state: Ontario
city: London
country: Canada
facility: Research Site
state: Ontario
city: London
country: Canada
facility: Research Site
state: Ontario
city: Newmarket
country: Canada
facility: Research Site
state: Ontario
city: Sarnia
country: Canada
facility: Research Site
state: Ontario
city: Thornhill
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Levis
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Saint-Marc-des-Carrieres
country: Canada
facility: Research Site
state: Quebec
city: Beroun
country: Czechia
facility: Research Site
city: Jilove u Prahy
country: Czechia
facility: Research Site
city: Pardubice
country: Czechia
facility: Research Site
city: Plzen - Severni Predmesti
country: Czechia
facility: Research Site
city: Plzen
country: Czechia
facility: Research Site
city: Praha - Klanovice
country: Czechia
facility: Research Site
city: Praha 10
country: Czechia
facility: Research Site
city: Praha 4
country: Czechia
facility: Research Site
city: Praha 4
country: Czechia
facility: Research Site
city: Praha
country: Czechia
facility: Research Site
city: Uherske Hradiste
country: Czechia
facility: Research Site
city: Aschaffenburg
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Eschweiler
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Gelnhausen
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Hof
country: Germany
facility: Research Site
city: Löhne
country: Germany
facility: Research Site
city: Lübeck
country: Germany
facility: Research Site
city: Magdeburg
country: Germany
facility: Research Site
city: Mannheim
country: Germany
facility: Research Site
city: Munster
country: Germany
facility: Research Site
city: Oldenburg
country: Germany
facility: Research Site
city: Pirna
country: Germany
facility: Research Site
city: Rhaunen
country: Germany
facility: Research Site
city: Villingen-Schwenningen
country: Germany
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: México
country: Mexico
facility: Research Site
city: México
country: Mexico
facility: Research Site
city: Veracruz
country: Mexico
facility: Research Site
city: Veracruz
country: Mexico
facility: Research Site
city: Chelyabinsk
country: Russian Federation
facility: Research Site
city: Ekaterinburg
country: Russian Federation
facility: Research Site
city: Izhevsk
country: Russian Federation
facility: Research Site
city: Kemerovo
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Perm
country: Russian Federation
facility: Research Site
city: Perm
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: St.Petersburg
country: Russian Federation
facility: Research Site
city: Vladikavkaz
country: Russian Federation
facility: Research Site
city: Volgograd
country: Russian Federation
facility: Research Site
city: Banska Bystrica
country: Slovakia
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Dolny Kubin
country: Slovakia
facility: Research Site
city: Levice
country: Slovakia
facility: Research Site
city: Lucenec
country: Slovakia
facility: Research Site
city: Malacky
country: Slovakia
facility: Research Site
city: Namestovo
country: Slovakia
facility: Research Site
city: Nitra
country: Slovakia
facility: Research Site
city: Nove Mesto nad Vahom
country: Slovakia
facility: Research Site
city: Prievidza
country: Slovakia
facility: Research Site
city: Rimavska Sobota
country: Slovakia
facility: Research Site
city: Roznava
country: Slovakia
facility: Research Site
city: Sabinov
country: Slovakia
facility: Research Site
city: Trebisov
country: Slovakia
facility: Research Site
city: Trencin
country: Slovakia
facility: Research Site
city: Trnava
country: Slovakia
facility: Research Site
city: Zilina
country: Slovakia
facility: Research Site
Study officials:
References:
citation: Nahra R, Wang T, Gadde KM, Oscarsson J, Stumvoll M, Jermutus L, Hirshberg B, Ambery P. Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults With Overweight or Obesity and Type 2 Diabetes: A 54-Week Randomized Phase 2b Study. Diabetes Care. 2021 Jun;44(6):1433-1442. doi: 10.2337/dc20-2151. Epub 2021 May 20.