Primary outcomeLeast squares mean· Baseline (Day 1) and Week 28
Adjusted Change From Baseline in Glycated Hemoglobin A1c (HbA1c) at Week 28
| Group | Value (percentage (%HbA1c)) | Spread |
|---|---|---|
| Total Exenatide Twice Daily (EBID) | 0.11 | 0.215 |
| Placebo | 0.38 | 0.293 |
Trial · Interventional
CompletedPhase 3Results postedRegistry dataSafety and Efficacy of Exenatide as Monotherapy and Adjunctive Therapy to Oral Antidiabetic Agents in Adolescents With Type 2 Diabetes
Overview
- Status
- Completed
- Phase
- Phase 3
- Enrollment
- 122 participants (actual)
- Sponsor
- AstraZeneca · Industry
- Design
- Randomized · Double masking
- Countries
8 countries
United States, Brazil, India, Mexico, Philippines, Russia, South Africa, South Korea
- Start
- 30 May 2008
- Primary completion
- 18 Apr 2019
- Completion
- 1 Apr 2020
- First posted
- 14 Apr 2008 (estimated)
- Last update posted
- 1 Dec 2020
- Conditions
- Type 2 Diabetes
Timeline
1 trial · 1 completed · 1 with posted results
- Completed
- Ongoing
- Not yet recruiting
- Stopped
- Estimated dates (est.)
- Results posted
201020152020
- Ph 3
Safety and Efficacy of Exenatide as Monotherapy and Adjunctive Therapy to Oral Antidiabetic Agents in Adolescents With Type 2 Diabetes
NCT0065802130 May 2008 to 1 Apr 2020
Registry summary
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
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
Interventions
- PlaceboDrug
- ExenatideDrug
- ExenatideDrug
Arms3
Placebo comparator
Placebo
Subcutaneous injection, twice a day
Experimental
Exenatide 5 µg
Subcutaneous injection, twice a day
Experimental
Exenatide 10 µg
Subcutaneous injection, twice a day
Primary outcomes2
Outcomes the sponsor listed as primary.
Adjusted Change From Baseline in Glycated Hemoglobin A1c (HbA1c) at Week 28
Time frame · Baseline (Day 1) and Week 28
Registry description
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.
Number of Participants With Post-Treatment Adverse Events of Special Interest (AESI) During Safety Follow-up Period
Time frame · From 1 day after the Week 28/ED visit to 3 years after Week 28/ED visit.
Registry description
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).
Secondary outcomes(7)
Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28
Time frame · Weeks 0, 4, 12, 20 and 28
Registry description
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.
Adjusted Change From Baseline in Body Weight Through Week 28
Time frame · Baseline (Day 1) up to Week 28
Registry description
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.
Adjusted Change From Baseline in Fasting Serum Glucose (FSG) at Week 28
Time frame · Baseline (Day 1) and Week 28
Registry description
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.
Adjusted Change From Baseline in Self-Monitored Blood Glucose (SMBG) at Week 28
Time frame · Pre-meal and 2 hours post-meal on Baseline (Day 1) and Week 28
Registry description
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.
Adjusted Change From Baseline in Fasting Serum Insulin at Week 28
Time frame · Baseline (Day 1) and Week 28
Registry description
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.
Adjusted Change From Baseline in Homeostasis Model Assessments - Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) at Week 28
Time frame · Baseline (Day 1) and Week 28
Registry description
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.
Percentage of Participants Discontinuing the Study Due to Failure to Maintain Glycemic Control Through Week 28
Time frame · Weeks 2, 4, 8, 12, 16, 20, 24 and 28
Registry description
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.
Posted results
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
Primary outcome results
Primary outcomeCount of participants· From 1 day after the Week 28/ED visit to 3 years after Week 28/ED visit.
Number of Participants With Post-Treatment Adverse Events of Special Interest (AESI) During Safety Follow-up Period
| Group | Value (Participants) |
|---|---|
| Exenatide 5 mcg | 0 |
| Exenatide 10 mcg | 0 |
| Placebo | 0 |
Secondary and other outcome results(6)
Secondary outcomeNumber· Weeks 0, 4, 12, 20 and 28
Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28
| Group | Value (percentage of participants) |
|---|---|
| Total Exenatide Twice Daily (EBID) | 37.2 |
| Placebo | 38.1 |
Secondary outcomeLeast squares mean· Baseline (Day 1) up to Week 28
Adjusted Change From Baseline in Body Weight Through Week 28
| Group | Value (kilogram) | Spread |
|---|---|---|
| Total Exenatide Twice Daily (EBID) | -0.89 | 0.196 |
| Placebo | 0.04 | 0.260 |
Secondary outcomeLeast squares mean· Baseline (Day 1) and Week 28
Adjusted Change From Baseline in Fasting Serum Glucose (FSG) at Week 28
| Group | Value (millimoles per liter (mmol/L)) | Spread |
|---|---|---|
| Total Exenatide Twice Daily (EBID) | 0.791 | 0.4010 |
| Placebo | 1.072 | 0.5466 |
Secondary outcomeLeast squares mean· Pre-meal and 2 hours post-meal on Baseline (Day 1) and Week 28
Adjusted Change From Baseline in Self-Monitored Blood Glucose (SMBG) at Week 28
| Group | Value (mmol/L) | Spread |
|---|---|---|
| Total Exenatide Twice Daily (EBID) | -0.699 | 0.2709 |
| Placebo | -0.888 | 0.4511 |
Secondary outcomeLeast squares mean· Baseline (Day 1) and Week 28
Adjusted Change From Baseline in Fasting Serum Insulin at Week 28
| Group | Value (picomoles per liter) | Spread |
|---|---|---|
| Total Exenatide Twice Daily (EBID) | 1.67 | 25.323 |
| Placebo | 12.49 | 34.825 |
Secondary outcomeLeast squares mean· Baseline (Day 1) and Week 28
Adjusted Change From Baseline in Homeostasis Model Assessments - Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) at Week 28
| Group | Value (percentage (%HOMA-B and %HOMA-S)) | Spread |
|---|---|---|
| Total Exenatide Twice Daily (EBID) | -25.93 | 10.404 |
| Placebo | -22.10 | 14.885 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Exenatide 5 mcgAdolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks. | 0 / 41 | 3 / 41 | 26 / 41 |
| Exenatide 10 mcgAdolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks. | 0 / 37 | 1 / 37 | 24 / 37 |
| PlaceboAdolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. | 0 / 42 | 1 / 42 | 23 / 42 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies0
Studies that cite this trial.
No study cites this trial.
Eligibility
Who could join, as posted.
- Sex
- All
- Age
- from 10 Years up to 17 Years
- Healthy volunteers
- Not accepted
Inclusion and exclusion criteria, as posted
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).
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