Safety and Efficacy of Exenatide as Monotherapy and Adjunctive Therapy to Oral Antidiabetic Agents in Adolescents With Type 2 Diabetes

Type 2 Diabetes Clinical Trial

Official title:

Safety and Efficacy of Exenatide as Monotherapy and Adjunctive Therapy to Oral Antidiabetic Agents in Adolescents With Type 2 Diabetes.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00658021
• Other study ID #: D5550C00002
• Secondary ID: H8O-MC-GWBQ
• Status: Completed
• Phase: Phase 3
• Start date: May 30, 2008
• Est. completion date: April 1, 2020

Study information

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

Clinical Trial Summary

The primary objective of this study is to test the hypothesis that glycemic control, as measured by change in hemoglobin A1c (HbA1c) from baseline to endpoint, with exenatide is superior to that of placebo after 28 weeks of treatment in adolescent patients with type 2 diabetes who are naïve to antidiabetes agents, or patients who are being treated with metformin, an SU, or a combination of metformin and an SU

Recruitment information / eligibility

• Status: Completed
• Enrollment: 122
• Est. completion date: April 1, 2020
• Est. primary completion date: April 18, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 17 Years

Eligibility

Inclusion Criteria-patients are eligible to be included in the study only if they meet all of the following criteria:

• are a male or a female between ages 10 to 17 years, inclusive. The number of patients =17 years of age will be limited to no more than 10% of patients in each treatment arm

• have a history of type 2 diabetes with the original diagnosis based on at least one American Diabetes Association (ADA) diagnostic criteria

• have been treated with metformin, an SU, or both metformin and an SU (with or without diet and exercise), for at least 3 months or are naïve to anti-diabetes agents and being treated with diet and exercise alone. The dose of oral agent(s) should be stable for the 30 days prior to the screening visit

• have fasting C-peptide >0.6 ng/mL

• have HbA1c between 6.5% and 10.5%, inclusive.

Disease Diagnostic Criteria-for the purposes of this study, patients with type 2 diabetes are defined by:

• diagnosis of type 2 diabetes, as determined by ADA diagnostic criteria and antibody testing, documented and confirmed in the patient's medical record, which includes laboratory determinations consistent with one or more of the following in the patient's medical history

• fasting blood glucose 126 mg/dL (7.0 mmol/L)

• random blood glucose 200 mg/dL (11.1 mmol/L)

• two-hour OGTT (Oral Glucose Tolerance Test) = 200 mg/dL (11.1 mmol/L) AND one or more of the following: no antibodies to GAD65 OR no antibodies to islet cell antigen (ICA512).

Exclusion Criteria-patients will be excluded from the study if they meet any of the following criteria:

• have previously been exposed to exenatide or, completed or withdrawn from this study or any other study investigating exenatide

• are unwilling or unable to inject the study medication

• currently use inhaled steroids at a dose equal to or above 1000g Flovent (fluticasone propionate) daily

• have used oral steroids within the last 60 days or more than 20 days use within the past year

• have used any weight loss medication(s) within 30 days of screening

• have used insulin for more than 10 weeks during the 3 months prior to screening

• have history of renal disease, or serum creatinine >1.6 mg/dL (141.4 µmol/L) (males) or >1.4 mg/dL (123.8 µmol/L) (females)

• have hepatic dysfunction, defined by aspartate (AST) or alanine (ALT) transaminase >3.0 times the upper limit of normal (ULN).

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Placebo
Subcutaneous injection, twice a day
• Exenatide
Subcutaneous injection, 5 µg, twice a day
• Exenatide
Subcutaneous injection,10 µg, twice a day

Locations

Country	Name	City	State
Brazil	Research Site	Fortaleza
Brazil	Research Site	Juiz de Fora
Brazil	Research Site	Santo André
India	Research Site	Ahmedabad
India	Research Site	Bangalore
India	Research Site	Pune
Korea, Republic of	Research Site	Seoul
Mexico	Research Site	Aguascalientes
Mexico	Research Site	Culiacán
Mexico	Research Site	Guadalajara
Mexico	Research Site	Monterrey
Mexico	Research Site	San Juan del Rio
Mexico	Research Site	Tamaupilas
Mexico	Research Site	Tampico
Philippines	Research Site	Quezon City
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Tomsk
Russian Federation	Research Site	Ufa
South Africa	Research Site	Moloto
South Africa	Research Site	Paarl
South Africa	Research Site	Pretoria
South Africa	Research Site	Verulam
United States	Research Site	Aurora	Colorado
United States	Research Site	Birmingham	Alabama
United States	Research Site	Chicago	Illinois
United States	Research Site	Chicago	Illinois
United States	Research Site	Dallas	Texas
United States	Research Site	Dalton	Georgia
United States	Research Site	Dearborn	Michigan
United States	Research Site	Greenville	North Carolina
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Jamaica	New York
United States	Research Site	Kansas City	Missouri
United States	Research Site	Los Angeles	California
United States	Research Site	Melbourne	Florida
United States	Research Site	Memphis	Tennessee
United States	Research Site	Miami	Florida
United States	Research Site	Miami Lakes	Florida
United States	Research Site	Montclair	California
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Orlando	Florida
United States	Research Site	Pensacola	Florida
United States	Research Site	Raleigh	North Carolina
United States	Research Site	Reno	Nevada
United States	Research Site	Sacramento	California
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	Santa Ana	California
United States	Research Site	Spokane	Washington
United States	Research Site	Tallahassee	Florida
United States	Research Site	Tucson	Arizona
United States	Research Site	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Quintiles, Inc.

Countries where clinical trial is conducted

United States,  Brazil,  India,  Korea, Republic of,  Mexico,  Philippines,  Russian Federation,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adjusted Change From Baseline in Glycated Hemoglobin A1c (HbA1c) at Week 28	Change from baseline in HbA1c is reported as adjusted least square (LS) mean values at Week 28. Baseline is defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of study medication. A mixed model with repeated measures (MMRM) analysis was performed, excluding measurements after initiation of rescue medication and study drug discontinuation.	Baseline (Day 1) and Week 28
Primary	Number of Participants With Post-Treatment Adverse Events of Special Interest (AESI) During Safety Follow-up Period	Post-treatment adverse events (AEs) were defined as AEs that started or worsened during the off-treatment period (Safety Follow-up Period), which was defined as the day after the Week 28/early discontinuation (ED) visit to the date of completion of the Safety Follow-up Period. The AESIs recorded were as follows: hematological malignancies, thyroid neoplasms, pancreas neoplasms, aplastic anemia, pancreatitis, pregnancy and pregnancy outcomes (including congenital anomalies).	From 1 day after the Week 28/ED visit to 3 years after Week 28/ED visit.
Secondary	Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28	The percentage of participants achieving HbA1c goals of < 7%, <= 6.5%, and < 6.5% through Week 28 were compared between treatments using the Cochran-Mantel-Haenszel (CMH) procedure, in which screening HbA1c strata and background diabetes therapy strata served as the stratification factors. The CMH analysis excluded measurements after initiation of rescue medication and study drug discontinuation with missing data treated as non-responder.	Weeks 0, 4, 12, 20 and 28
Secondary	Adjusted Change From Baseline in Body Weight Through Week 28	Change from baseline in body weight is reported as adjusted LS mean values at Weeks 4, 12, 20 and 28. Baseline is defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of study medication. A MMRM analysis was performed, excluding measurements after initiation of rescue medication and study drug discontinuation.	Baseline (Day 1) up to Week 28
Secondary	Adjusted Change From Baseline in Fasting Serum Glucose (FSG) at Week 28	Change from baseline in FSG is reported as adjusted LS mean values at Week 28. Baseline is defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of study medication. An analysis of covariance (ANCOVA) analysis was performed, excluding measurements after initiation of rescue medication and study drug discontinuation.	Baseline (Day 1) and Week 28
Secondary	Adjusted Change From Baseline in Self-Monitored Blood Glucose (SMBG) at Week 28	Change from baseline in SMBG measurements are reported as adjusted LS mean values at Week 28. SMBG measurements were taken before (pre-prandial) and 2 hours after (post-prandial) the 2 main meals of the day on 3 separate days during the week before baseline (Day 1) and Week 28. Post-prandial excursions were calculated as the difference between the pre-prandial and post-prandial blood glucose concentrations (post-prandial - pre-prandial) and averaged (mean) over the 2 main meals over the 3 separate days in each period. Baseline is defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of study medication. An ANCOVA analysis was performed, excluding measurements after initiation of rescue medication and study drug discontinuation.	Pre-meal and 2 hours post-meal on Baseline (Day 1) and Week 28
Secondary	Adjusted Change From Baseline in Fasting Serum Insulin at Week 28	Change from baseline in fasting serum insulin is reported as adjusted LS mean values at Week 28. Baseline is defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of study medication. An ANCOVA analysis was performed, excluding measurements after initiation of rescue medication and study drug discontinuation.	Baseline (Day 1) and Week 28
Secondary	Adjusted Change From Baseline in Homeostasis Model Assessments - Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) at Week 28	Change from baseline in HOMA-B and HOMA-S are reported as adjusted LS mean values at Week 28. Baseline is defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of study medication. An ANCOVA analysis was performed, excluding measurements after initiation of rescue medication and study drug discontinuation.	Baseline (Day 1) and Week 28
Secondary	Percentage of Participants Discontinuing the Study Due to Failure to Maintain Glycemic Control Through Week 28	Participants were discontinued from the study due to failure to maintain glycemic control if either discontinuation reason on summary case report form was "Loss of glucose control" or AE with lower level Medical Dictionary for Regulatory Activities (MedDRA) term "Loss of control of blood sugar" or "Hyperglycaemia" leading to study drug discontinuation, using MedDRA Version 23.0.	Weeks 2, 4, 8, 12, 16, 20, 24 and 28

External Links

•   Clinical_Study_Protocol_redacted
•   Statistical Analysis Plan_redacted