A Study to Evaluate the Efficacy and Safety of MEDI0382 in the Treatment of Overweight and Obese Subjects With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03235050
• Other study ID #: D5670C00004
• Status: Completed
• Phase: Phase 2
• Start date: August 2, 2017
• Est. completion date: June 14, 2019

Study information

• Verified date: July 2020
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 834
• Est. completion date: June 14, 2019
• Est. primary completion date: May 3, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Overweight

Intervention

Drug:
• MEDI0382 low dose
Pharmaceutical form: solution Route of administration: subcutaneous
• MEDI0382 mid dose
Pharmaceutical form: solution Route of administration: subcutaneous
• MEDI0382 high dose
Pharmaceutical form: solution Route of administration: subcutaneous
• Placebo
Pharmaceutical form: solution Route of administration: subcutaneous
• Liraglutide
Pharmaceutical form: solution Route of administration: subcutaneous

Locations

Country	Name	City	State
Bulgaria	Research Site	Botevgrad
Bulgaria	Research Site	Kozloduy
Bulgaria	Research Site	Kyustendil
Bulgaria	Research Site	Lukovit
Bulgaria	Research Site	Petrich
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Russe
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Stara Zagora
Canada	Research Site	Burlington	Ontario
Canada	Research Site	Etobicoke	Ontario
Canada	Research Site	Guelph	Ontario
Canada	Research Site	Levis	Quebec
Canada	Research Site	London	Ontario
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Newmarket	Ontario
Canada	Research Site	Red Deer	Alberta
Canada	Research Site	Saint-Marc-des-Carrieres	Quebec
Canada	Research Site	Sarnia	Ontario
Canada	Research Site	Sherwood Park	Alberta
Canada	Research Site	Thornhill	Ontario
Canada	Research Site	Toronto	Ontario
Czechia	Research Site	Beroun
Czechia	Research Site	Jilove u Prahy
Czechia	Research Site	Pardubice
Czechia	Research Site	Plzen
Czechia	Research Site	Plzen - Severni Predmesti
Czechia	Research Site	Praha
Czechia	Research Site	Praha - Klanovice
Czechia	Research Site	Praha 10
Czechia	Research Site	Praha 4
Czechia	Research Site	Praha 4
Czechia	Research Site	Uherske Hradiste
Germany	Research Site	Aschaffenburg
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Eschweiler
Germany	Research Site	Essen
Germany	Research Site	Essen
Germany	Research Site	Gelnhausen
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Hof
Germany	Research Site	Löhne
Germany	Research Site	Lübeck
Germany	Research Site	Magdeburg
Germany	Research Site	Mannheim
Germany	Research Site	Munster
Germany	Research Site	Oldenburg
Germany	Research Site	Pirna
Germany	Research Site	Rhaunen
Germany	Research Site	Villingen-Schwenningen
Mexico	Research Site	Guadalajara
Mexico	Research Site	México
Mexico	Research Site	México
Mexico	Research Site	Monterrey
Mexico	Research Site	Veracruz
Mexico	Research Site	Veracruz
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Izhevsk
Russian Federation	Research Site	Kemerovo
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Perm
Russian Federation	Research Site	Perm
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St.Petersburg
Russian Federation	Research Site	Vladikavkaz
Russian Federation	Research Site	Volgograd
Slovakia	Research Site	Banska Bystrica
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Dolny Kubin
Slovakia	Research Site	Levice
Slovakia	Research Site	Lucenec
Slovakia	Research Site	Malacky
Slovakia	Research Site	Namestovo
Slovakia	Research Site	Nitra
Slovakia	Research Site	Nove Mesto nad Vahom
Slovakia	Research Site	Prievidza
Slovakia	Research Site	Rimavska Sobota
Slovakia	Research Site	Roznava
Slovakia	Research Site	Sabinov
Slovakia	Research Site	Trebisov
Slovakia	Research Site	Trencin
Slovakia	Research Site	Trnava
Slovakia	Research Site	Zilina
United States	Research Site	Arlington	Virginia
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Birmingham	Alabama
United States	Research Site	Bridgeton	Missouri
United States	Research Site	Brooklyn	New York
United States	Research Site	Chandler	Arizona
United States	Research Site	Elkridge	Maryland
United States	Research Site	Evansville	Indiana
United States	Research Site	Glendale	Arizona
United States	Research Site	Glendale	Arizona
United States	Research Site	Greer	South Carolina
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Layton	Utah
United States	Research Site	Manassas	Virginia
United States	Research Site	Marietta	Georgia
United States	Research Site	Mesa	Arizona
United States	Research Site	Metairie	Louisiana
United States	Research Site	Morehead City	North Carolina
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Plano	Texas

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	MedImmune LLC

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Czechia,  Germany,  Mexico,  Russian Federation,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c	To assess the effect of 100, 200, 300 µg of cotadutide on HbA1c versus placebo	From baseline to 14 weeks
Primary	Percent Change in Body Weight	To assess the effect of 100, 200, 300 µg of cotadutide on body weight versus placebo	From baseline to 14 weeks
Secondary	Change in HbA1c	To assess the effect of 100, 200, 300 µg of cotadutide on HbA1c versus placebo	from baseline to 26 weeks and 54 weeks
Secondary	Percentage of Participants Achieving an HbA1c Target < 7.0%	To assess the effect of 100, 200, and 300 µg of cotadutide on percentage of participants achieving an HbA1c target of <7% versus placebo	after 14, 26, and 54 weeks
Secondary	Percent Change in Body Weight	To assess the effect of 100, 200, and 300 µg of cotadutide on body weight versus placebo	from baseline to 26 weeks and 54 weeks
Secondary	Absolute Change in Body Weight	To assess the effect of 100, 200, 300 µg of cotadutide on body weight versus placebo	from baseline to 14 weeks, 26 weeks and 54 weeks
Secondary	Percent Change in Body Weight Versus Active Comparator	To assess the effect of 100, 200, and 300 µg of cotadutide on body weight versus liraglutide 1.8 mg once daily	from baseline to 14 weeks, 26 weeks and 54 weeks
Secondary	Absolute Change in Body Weight Versus Active Comparator	To assess the effect of 100, 200, and 300 µg of cotadutide on body weight versus liraglutide 1.8 mg once daily	from baseline to 14 weeks, 26 weeks and 54 weeks
Secondary	Percentage of Participants Achieving Weight Loss of =5% and =10%	To assess the effect of 100, 200, and 300 µg of cotadutide on percentage of subjects achieving weight loss of =5% and =10% versus placebo	after 14 weeks, 26 weeks and 54 weeks
Secondary	Percentage of Participants Rescued or Discontinued for Lack of Glycaemic Control	To assess the effect of 100, 200, and 300 µg of cotadutide on the requirement for additional blood glucose-lowering therapies versus placebo	at 14 weeks, 26 weeks and 54 weeks
Secondary	Pharmacokinetic (PK) Endpoint: Trough Plasma Concentration (Cmin)	To characterise the PK profile of 100, 200, and 300 µg of cotadutide	Time points at which outcome measure were assessed for plasma concentration were Weeks 1,2,6,10,14,18,22,26, and 54
Secondary	Immunogenicity Endpoint: Overall Antidrug Antibody (ADA) Incidence (Number and Percentage of Positive Partipants)	To characterise the immunogenicity of 100, 200, and 300 µg of cotadutide	Baseline through 54-week treatment period and 28-day follow-up
Secondary	Immunogenicity Endpoint: Median Titer of the Anti-Drug Antibodies (ADA) to MEDI0382 in the Positive Participants	To characterise the immunogenicity of 100, 200, and 300 µg of cotadutide	Baseline through 54-week treatment period and 28-day follow-up

External Links

•   D5670C00004 CSP redacted
•   D5670C00004 SAP redacted