A Phase 3 interventional study of Exenatide Once Weekly and Placebo in Children and Adolescent With Type 2 Diabetes, sponsored by AstraZeneca. Completed at 35 sites in 7 countries. Open to participants aged 10 Years to 17 Years. Per ClinicalTrials.gov, last updated 2021-11-30.
Sponsored by AstraZeneca · Phase 3, Interventional, and Treatment
The study examines the Safety and efficacy study of exenatide once weekly in children and adolescents with type 2 diabetes
This Phase 3, double-blind (controlled assessment period), randomized, multicenter, placebo-controlled parallel study is designed to examine the efficacy and safety of EQW compared to placebo (PBO) in adolescents with type 2 diabetes for 24 weeks. This study will assess safety and efficacy of EQW (as monotherapy and adjunctive therapy to oral antidiabetic agents and/or insulin). At least 40% and not more than 60% of the randomized patients must be females. At least 40% of patients should be recruited from areas with similar ethnicity and lifestyle to those of the European Union member states. Long term safety and efficacy of EQW will subsequently be monitored for 28 weeks in the open-label, uncontrolled extension period (through Week 52). The study will be terminated at Visit 11 (Week 62/Study Termination) which will be a follow-up visit occurring 10 weeks after the last dose administration at Visit 10 (Week 52). This study will be conducted in 77 patients with type 2 diabetes treated with diet and exercise alone or in combination with a stable dose of oral antidiabetic agents and/or insulin for at least 2 months prior to screening. During the controlled assessment period, approximately 77 patients will be randomly assigned in a 5:2 ratio to either EQW 2 mg (Group A) or PBO (Group B), to yield at least 70 evaluable patients: at least 50 patients in the exenatide and at least 20 patients in the PBO group. Following the 24-week controlled assessment period, patients assigned to the EQW 2 mg treatment (Group A) will continue to be treated with EQW 2 mg during the extension period (through Week 52). Patients randomized to PBO (Group B) will receive EQW 2 mg beginning at the start of the extension period, Week 25 through Week 52. In addition to receiving study medications, all patients will participate in a lifestyle intervention program encompassing diet and physical activity modifications following the signing of the informed consent and assent forms (Visit 1 [Week -2]) through the end of the extension period (Week 52). Following Visit 11 (Week 62/Study Termination), patients whose height increase is at least 5 mm between Visit 8 (Week 28) and Visit 11 (Week 62/Study Termination) will participate in a long-term safety follow-up period. Patients who discontinue study medication prior to Visit 11 (Week 62/Study Termination) will also participate in the Extended Safety Follow-up Period, unless they have a height increase of less than 5 mm over a 6-month interval at study site visits prior to discontinuation of study medication. Patients who do not have height assessments at study-site visits over a 6-month interval prior to discontinuation of study medication will enter the Extended Safety Follow-up Period. The Extended Safety Follow Up Period will continue for up to 3 years or until the difference between two 6-month interval visits is less than a 5 mm increase (whichever comes first). No study medication will be administered during the Extended Safety Follow-up Period. Blood samples will be collected for calcitonin and carcinoembryonic antigen (CEA) laboratory measurements.
10,925 studies on the registry are indexed under Diabetes Mellitus; 1,319 are open to participants now.
This study's enrollment of 84 is close to the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.
Browse Diabetes Mellitus studies →AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.
Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.
Counted across the registry records on this site, refreshed daily.
Each patient must meet the following criteria to be enrolled in this study.
Patients who meet any of the following criteria will be excluded from the study.
Has a clinically significant medical condition that could potentially affect study participation and/or personal well-being, as judged by the Investigator, including but not limited to the following conditions:
Exenatide once weekly
Drug: Exenatide Once Weekly
Placebo once weekly
Drug: Placebo
2 mg exenatide once weekly
Also known as: BYDUREON
Placebo
Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) to Week 24 (Controlled Assessment Period)
Change from baseline in HbA1c (%) to Week 24 during the controlled assessment period is reported as adjusted least square (LS) mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A mixed model with repeated measures (MMRM) analysis was performed, excluding data collected after initiation of rescue medication or premature discontinuation of study medication.
Time frame: Baseline (Week 0) and Week 24
Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period)
A controlled assessment period AE was defined as an AE starting on or after day of first dose of study medication up to but not including Week 24 for patients entering the extension period. For patients not entering the extension period, the period was defined up to and including last dose of study medication + 7 days (+ 90 days for serious AEs \[SAEs\] and other clinically significant or related AEs). The Investigator assessed AEs for causal relationship to study drug medication.
Time frame: Day 1 (Week 0) up to Week 24, plus up to a maximum of 90 days follow up
Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24
Percentage of patients positive for ADAs up to Week 24 for the exenatide treatment group is reported. Baseline was the antibody measurement at Week 0 (Day 1). A negative or missing antibody measurement was considered negative at baseline. High positive = antibody titers ≥ 625, including baseline assessment. Low positive = antibody titers \< 625, including baseline assessment. A patient was said to have treatment-emergent ADA positive at a visit if the antibody test was positive after the first dose of exenatide following a negative or missing antibody measurement, or the titer increased by at least 1 titration category from a detectable measurement prior to first dose of randomized study medication.
Time frame: Samples were collected on Day 1 (Week 0), Week 4, Week 8, Week 12 and Week 24
Change From Baseline in Fasting Plasma Glucose (FPG) Concentration to Week 24 (Controlled Assessment Period)
Change from baseline in FPG to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time frame: Baseline (Week 0) and Week 24
Change From Baseline in Body Weight to Week 24 (Controlled Assessment Period)
Change from baseline in body weight to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time frame: Baseline (Week 0) and Week 24
Change From Baseline in Fasting Insulin to Week 24 (Controlled Assessment Period)
Change from baseline in fasting insulin to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time frame: Baseline (Week 0) and Week 24
Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period)
The percentage of patients achieving HbA1c goals of \< 6.5%, ≤ 6.5%, and \< 7.0% at Week 24 during the controlled assessment period is reported. A Cochran-Mantel-Haenszel (CMH) analysis was performed with missing data treated as non-responder, and excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time frame: At Week 24
Change From Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period)
Change from baseline in lipid profiles to Week 24 during the controlled assessment period is reported as mean values (Standard International \[SI\] units). The following lipids were assessed: total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides. All lipids presented were taken in a fasted state. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time frame: Baseline (Week 0) and Week 24
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) to Week 24 (Controlled Assessment Period)
Change from baseline in SBP and DBP to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time frame: Baseline (Week 0) and Week 24
Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period)
Number of patients needing rescue medication at Week 24 and at each intermediate visit during the controlled assessment period is reported. Patients with a loss of glycemic control, defined as either an increase from baseline in HbA1c values by ≥ 1.0% at 2 consecutive clinic visits that were at least 1 month apart, or a fasting plasma glucose value ≥ 250 mg/dL or random blood glucose value \> 300 mg/dL for 4 days during a 7 day period, received rescue medication. Data collected after premature discontinuation of study medication were excluded.
Time frame: At Week 4, Week 8, Week 12, Week 18 and Week 24
Change From Baseline in Homeostasis Model Assessments - Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) to Week 24 (Controlled Assessment Period)
Change from baseline in HOMA-B and HOMA-S in patients who were not taking insulin to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time frame: Baseline (Week 0) and Week 24
Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period)
Percentage of patients reporting injection site reactions at Week 24 and at each intermediate visit during the controlled assessment period is reported. Injection site reactions were presented from the AE case report form (CRF), based on the "Injection site reactions" higher level term. A controlled assessment period AE was defined as an AE starting on or after day of first dose of study medication up to but not including Week 24 for patients entering the extension period. For patients not entering the extension period, the period was defined up to and including last dose of study medication + 7 days (+ 90 days for SAEs and other clinically significant or related AEs).
Time frame: At Week 4, Week 8, Week 12, Week 18 and Week 24
Change From Baseline in HbA1c to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Change from baseline in HbA1c (%) to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time frame: Baseline (Week 0) and Week 52
Change From Baseline in FPG Concentration to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Change from baseline in FPG to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time frame: Baseline (Week 0) and Week 52
Change From Baseline in Body Weight to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Change from baseline in body weight to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time frame: Baseline (Week 0) and Week 52
Change From Baseline in Fasting Insulin to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Change from baseline in fasting insulin to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time frame: Baseline (Week 0) and Week 52
Percentage of Participants Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
The percentage of patients achieving HbA1c goals of \< 6.5%, ≤ 6.5%, and \< 7.0% at Week 52 among patients who received open-label exenatide during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time frame: At Week 52
Change From Baseline in Lipids Profiles to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Change from baseline in lipid profiles to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values (SI units). The treatment period was defined as the controlled assessment period and extension period combined. The following lipids were assessed: total cholesterol, HDL-C, LDL-C, and triglycerides. All lipids presented were taken in a fasted state. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time frame: Baseline (Week 0) and Week 52
Change From Baseline in Blood Pressure (Systolic and Diastolic) to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Change from baseline in SBP and DBP to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time frame: Baseline (Week 0) and Week 52
Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Number of patients needing rescue medication at Week 52 and at each intermediate visit during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Patients with a loss of glycemic control, defined as either an increase from baseline in HbA1c values by ≥ 1.0% at 2 consecutive clinic visits that were at least 1 month apart, or a fasting plasma glucose value ≥ 250 mg/dL or random blood glucose value \> 300 mg/dL for 4 days during a 7 day period, received rescue medication. Data collected after premature discontinuation of study medication were excluded.
Time frame: At Week 4, Week 8, Week 12, Week 18, Week 24, Week 28, Week 40 and Week 52
Change From Baseline in HOMA-B and HOMA-S to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Change from baseline in HOMA-B and HOMA-S to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time frame: Baseline (Week 0) and Week 52
Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Percentage of patients reporting injection site reactions at Week 52 and at each intermediate visit among patients who received open-label exenatide during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Injection site reactions were presented from the AE CRF, based on the "Injection site reactions" higher level term. An Extension Period AE was defined as an AE starting on or after day of first dose of open-label exenatide to last dose + 7 days (+ 90 days for SAEs and other clinically significant or related AEs).
Time frame: At Week 4, Week 8, Week 12, Week 18, Week 24, Week 28, Week 40 and Week 52
Plasma Exenatide Concentrations to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Geometric mean plasma exenatide concentrations up to Week 52 during the treatment period are reported (for the placebo then exenatide treatment group, only Weeks 24 and 52 were applicable). The treatment period was defined as the controlled assessment period and extension period combined. Data collected after initiation of rescue medication were included. Data collected after discontinuation of study medication were excluded.
Time frame: Samples were collected on Day 1 (Week 0), Week 4, Week 8, Week 12, Week 24 and Week 52
This study was conducted in adolescents (aged 10 to 17 years inclusive) with type 2 diabetes treated with diet and exercise alone or in combination with a stable dose of oral antidiabetic agents and/or insulin for at least 2 months prior to screening. 27 study centers in 6 countries randomized patients during the study.
| Milestone | Exenatide | Placebo |
|---|---|---|
| Started | 59 | 24 |
| Completed | 58 | 24 |
| Not completed | 1 | 0 |
| Withdrew: Adverse event | 1 | 0 |
| Milestone | Exenatide | Placebo |
|---|---|---|
| Started | 58 | 24 |
| Completed | 50 | 23 |
| Not completed | 8 | 1 |
| Withdrew: Lost to follow-up | 2 | 1 |
| Withdrew: Withdrawal by subject | 6 | 0 |
| Milestone | Exenatide | Placebo |
|---|---|---|
| Started | 49 | 23 |
| Completed | 46 | 18 |
| Not completed | 3 | 5 |
| Withdrew: Withdrawal by subject | 2 | 3 |
| Withdrew: Physician decision | 0 | 1 |
| Withdrew: Lost to follow-up | 1 | 1 |
Change from baseline in HbA1c (%) to Week 24 during the controlled assessment period is reported as adjusted least square (LS) mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A mixed model with repeated measures (MMRM) analysis was performed, excluding data collected after initiation of rescue medication or premature discontinuation of study medication.
| percentage (% HbA1c) | Controlled Assessment Period - Exenatide | Controlled Assessment Period - Placebo |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) to Week 24 (Controlled Assessment Period) | -0.36 ± 0.184 | 0.49 ± 0.273 |
A controlled assessment period AE was defined as an AE starting on or after day of first dose of study medication up to but not including Week 24 for patients entering the extension period. For patients not entering the extension period, the period was defined up to and including last dose of study medication + 7 days (+ 90 days for serious AEs \[SAEs\] and other clinically significant or related AEs). The Investigator assessed AEs for causal relationship to study drug medication.
| percentage of participants | Controlled Assessment Period - Exenatide | Controlled Assessment Period - Placebo |
|---|---|---|
| Any AE | 61.0 | 73.9 |
| Any AE with outcome of death | 0 | 0 |
| Any SAE | 3.4 | 4.3 |
| Any AE leading to discontinuation of treatment | 0 | 0 |
| Any AE leading to discontinuation from study | 0 | 0 |
| Any AE related to treatment | 25.4 | 21.7 |
Percentage of patients positive for ADAs up to Week 24 for the exenatide treatment group is reported. Baseline was the antibody measurement at Week 0 (Day 1). A negative or missing antibody measurement was considered negative at baseline. High positive = antibody titers ≥ 625, including baseline assessment. Low positive = antibody titers \< 625, including baseline assessment. A patient was said to have treatment-emergent ADA positive at a visit if the antibody test was positive after the first dose of exenatide following a negative or missing antibody measurement, or the titer increased by at least 1 titration category from a detectable measurement prior to first dose of randomized study medication.
| percentage of participants | Treatment Period - Exenatide |
|---|---|
| Week 4: High Positive | 17.0 |
| Week 4: Low Positive | 30.2 |
| Week 4: Treatment-Emergent ADA Positive | 45.3 |
| Week 8: High Positive | 53.8 |
| Week 8: Low Positive | 38.5 |
| Week 8: Treatment-Emergent ADA Positive | 92.3 |
| Week 12: High Positive | 60.0 |
| Week 12: Low Positive | 38.0 |
| Week 12: Treatment-Emergent ADA Positive | 98.0 |
| Week 24: High Positive | 40.8 |
| Week 24: Low Positive | 55.1 |
| Week 24: Treatment-Emergent ADA Positive | 95.9 |
Change from baseline in FPG to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
| milligrams per deciliter (mg/dL) | Controlled Assessment Period - Exenatide | Controlled Assessment Period - Placebo |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose (FPG) Concentration to Week 24 (Controlled Assessment Period) | -5.2 ± 7.65 | 16.5 ± 11.32 |
Change from baseline in body weight to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
| kilogram (kg) | Controlled Assessment Period - Exenatide | Controlled Assessment Period - Placebo |
|---|---|---|
| Change From Baseline in Body Weight to Week 24 (Controlled Assessment Period) | -0.59 ± 0.665 | 0.63 ± 0.982 |
Change from baseline in fasting insulin to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
| picomoles per liter (pmol/L) | Controlled Assessment Period - Exenatide | Controlled Assessment Period - Placebo |
|---|---|---|
| Change From Baseline in Fasting Insulin to Week 24 (Controlled Assessment Period) | 79.6 ± 52.28 | -15.3 ± 78.49 |
The percentage of patients achieving HbA1c goals of \< 6.5%, ≤ 6.5%, and \< 7.0% at Week 24 during the controlled assessment period is reported. A Cochran-Mantel-Haenszel (CMH) analysis was performed with missing data treated as non-responder, and excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
| percentage of participants | Controlled Assessment Period - Exenatide | Controlled Assessment Period - Placebo |
|---|---|---|
| HbA1c <6 .5% | 19.0 (8.9 to 29.1) | 4.2 (0.0 to 12.2) |
| HbA1c ≤ 6.5% | 19.0 (8.9 to 29.1) | 4.2 (0.0 to 12.2) |
| HbA1c < 7.0% | 31.0 (19.1 to 42.9) | 8.3 (0.0 to 19.4) |
Change from baseline in lipid profiles to Week 24 during the controlled assessment period is reported as mean values (Standard International \[SI\] units). The following lipids were assessed: total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides. All lipids presented were taken in a fasted state. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
| millimoles per liter (mmol/L) | Controlled Assessment Period - Exenatide | Controlled Assessment Period - Placebo |
|---|---|---|
| Total Cholesterol | -0.117 ± 0.7124 | -0.114 ± 0.5819 |
| HDL-C | -0.035 ± 0.1950 | -0.047 ± 0.1039 |
| LDL-C | -0.050 ± 0.5618 | -0.110 ± 0.5983 |
| Triglycerides | -0.122 ± 1.0303 | 0.094 ± 0.6626 |
Change from baseline in SBP and DBP to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
| millimeters mercury (mmHg) | Controlled Assessment Period - Exenatide | Controlled Assessment Period - Placebo |
|---|---|---|
| SBP | -0.7 ± 1.48 | 2.2 ± 2.15 |
| DBP | 0.2 ± 1.00 | -1.3 ± 1.45 |
Number of patients needing rescue medication at Week 24 and at each intermediate visit during the controlled assessment period is reported. Patients with a loss of glycemic control, defined as either an increase from baseline in HbA1c values by ≥ 1.0% at 2 consecutive clinic visits that were at least 1 month apart, or a fasting plasma glucose value ≥ 250 mg/dL or random blood glucose value \> 300 mg/dL for 4 days during a 7 day period, received rescue medication. Data collected after premature discontinuation of study medication were excluded.
| Participants | Controlled Assessment Period - Exenatide | Controlled Assessment Period - Placebo |
|---|---|---|
| Week 4 | 0 | 0 |
| Week 8 | 0 | 0 |
| Week 12 | 0 | 0 |
| Week 18 | 1 | 0 |
| Week 24 | 0 | 0 |
Change from baseline in HOMA-B and HOMA-S in patients who were not taking insulin to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
| percentage (%HOMA-B and %HOMA-S) | Controlled Assessment Period - Exenatide | Controlled Assessment Period - Placebo |
|---|---|---|
| HOMA-B | 63.98 ± 39.552 | -26.39 ± 56.138 |
| HOMA-S | 0.62 ± 3.607 | 7.37 ± 4.914 |
Percentage of patients reporting injection site reactions at Week 24 and at each intermediate visit during the controlled assessment period is reported. Injection site reactions were presented from the AE case report form (CRF), based on the "Injection site reactions" higher level term. A controlled assessment period AE was defined as an AE starting on or after day of first dose of study medication up to but not including Week 24 for patients entering the extension period. For patients not entering the extension period, the period was defined up to and including last dose of study medication + 7 days (+ 90 days for SAEs and other clinically significant or related AEs).
| percentage of participants | Controlled Assessment Period - Exenatide | Controlled Assessment Period - Placebo |
|---|---|---|
| Week 4 | 8.5 | 8.7 |
| Week 8 | 3.5 | 4.3 |
| Week 12 | 1.9 | 0 |
| Week 18 | 0 | 0 |
| Week 24 | 0 | 0 |
Change from baseline in HbA1c (%) to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
| percentage (% HbA1c) | Treatment Period - Exenatide | Treatment Period - Placebo Then Exenatide |
|---|---|---|
| Change From Baseline in HbA1c to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | -0.10 ± 1.711 | 0.53 ± 2.123 |
Change from baseline in FPG to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
| mg/dL | Treatment Period - Exenatide | Treatment Period - Placebo Then Exenatide |
|---|---|---|
| Change From Baseline in FPG Concentration to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | -1.8 ± 62.64 | 10.6 ± 75.49 |
Change from baseline in body weight to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
| kg | Treatment Period - Exenatide | Treatment Period - Placebo Then Exenatide |
|---|---|---|
| Change From Baseline in Body Weight to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | 0.04 ± 6.088 | -0.04 ± 4.687 |
Change from baseline in fasting insulin to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
| pmol/L | Treatment Period - Exenatide | Treatment Period - Placebo Then Exenatide |
|---|---|---|
| Change From Baseline in Fasting Insulin to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | -32.4 ± 273.57 | 121.5 ± 379.13 |
The percentage of patients achieving HbA1c goals of \< 6.5%, ≤ 6.5%, and \< 7.0% at Week 52 among patients who received open-label exenatide during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
| percentage of participants | Treatment Period - Exenatide | Treatment Period - Placebo Then Exenatide |
|---|---|---|
| HbA1c < 6.5% | 30.8 | 23.5 |
| HbA1c ≤ 6.5% | 30.8 | 23.5 |
| HbA1c < 7.0% | 35.9 | 29.4 |
Change from baseline in lipid profiles to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values (SI units). The treatment period was defined as the controlled assessment period and extension period combined. The following lipids were assessed: total cholesterol, HDL-C, LDL-C, and triglycerides. All lipids presented were taken in a fasted state. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
| mmol/L | Treatment Period - Exenatide | Treatment Period - Placebo Then Exenatide |
|---|---|---|
| Total Cholesterol | -0.188 ± 0.4199 | -0.255 ± 0.9075 |
| HDL-C | 0.004 ± 0.1740 | -0.076 ± 0.2327 |
| LDL-C | -0.175 ± 0.4025 | -0.152 ± 0.7682 |
| Triglycerides | -0.155 ± 1.1108 | -0.043 ± 0.5971 |
Change from baseline in SBP and DBP to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
| mmHg | Treatment Period - Exenatide | Treatment Period - Placebo Then Exenatide |
|---|---|---|
| SBP | -0.7 ± 13.09 | -0.6 ± 8.73 |
| DBP | 1.1 ± 8.65 | -2.5 ± 10.65 |
Number of patients needing rescue medication at Week 52 and at each intermediate visit during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Patients with a loss of glycemic control, defined as either an increase from baseline in HbA1c values by ≥ 1.0% at 2 consecutive clinic visits that were at least 1 month apart, or a fasting plasma glucose value ≥ 250 mg/dL or random blood glucose value \> 300 mg/dL for 4 days during a 7 day period, received rescue medication. Data collected after premature discontinuation of study medication were excluded.
| Participants | Treatment Period - Exenatide | Treatment Period - Placebo Then Exenatide |
|---|---|---|
| Week 4 | 0 | 0 |
| Week 8 | 0 | 0 |
| Week 12 | 0 | 0 |
| Week 18 | 1 | 0 |
| Week 24 | 0 | 0 |
| Week 28 | 2 | 1 |
| Week 40 | 2 | 0 |
| Week 52 | 0 | 0 |
Change from baseline in HOMA-B and HOMA-S to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
| percentage (%HOMA-B and %HOMA-S) | Treatment Period - Exenatide | Treatment Period - Placebo Then Exenatide |
|---|---|---|
| HOMA-B | -2.58 ± 130.435 | 42.02 ± 183.869 |
| HOMA-S | 9.85 ± 12.366 | 2.36 ± 7.631 |
Percentage of patients reporting injection site reactions at Week 52 and at each intermediate visit among patients who received open-label exenatide during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Injection site reactions were presented from the AE CRF, based on the "Injection site reactions" higher level term. An Extension Period AE was defined as an AE starting on or after day of first dose of open-label exenatide to last dose + 7 days (+ 90 days for SAEs and other clinically significant or related AEs).
| percentage of participants | Treatment Period - Exenatide | Treatment Period - Placebo Then Exenatide |
|---|---|---|
| Week 4 | 10.0 | 9.1 |
| Week 8 | 4.0 | 4.5 |
| Week 12 | 2.0 | 0 |
| Week 18 | 0 | 0 |
| Week 24 | 0 | 0 |
| Week 28 | 4.0 | 0 |
| Week 40 | 0 | 0 |
| Week 52 | 0 | 0 |
Geometric mean plasma exenatide concentrations up to Week 52 during the treatment period are reported (for the placebo then exenatide treatment group, only Weeks 24 and 52 were applicable). The treatment period was defined as the controlled assessment period and extension period combined. Data collected after initiation of rescue medication were included. Data collected after discontinuation of study medication were excluded.
| picograms per milliliter | Treatment Period - Exenatide | Treatment Period - Placebo Then Exenatide |
|---|---|---|
| Baseline | NA ± NA | — |
| Week 4 | 41.51 ± 91.9 | — |
| Week 8 | 130.60 ± 83.8 | — |
| Week 12 | 163.58 ± 92.3 | — |
| Week 24 | 140.81 ± 84.0 | NA ± NA |
| Week 52 | 88.88 ± 79.2 | 105.56 ± 154.9 |
Collected over After the first dose of study medication in period through the end of the treatment in period + 90 days for SAEs (or + 7 days for non-serious (i.e. Other) AEs. Overall time frame: up to maximum of approximately 37 weeks and 41 weeks for controlled assessment period and extension period, respectively.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Controlled Assessment Period - Exenatide | 0/59 (0%) | 2/59 (3.4%) | 25/59 (42.4%) |
| Controlled Assessment Period - Placebo | 0/23 (0%) | 1/23 (4.3%) | 10/23 (43.5%) |
| Extension Period - Exenatide | 0/50 (0%) | 3/50 (6%) | 10/50 (20%) |
| Extension Period - Placebo to Exenatide | 0/22 (0%) | 1/22 (4.5%) | 4/22 (18.2%) |
| Event | Controlled Assessment Period - Exenatide | Controlled Assessment Period - Placebo | Extension Period - Exenatide | Extension Period - Placebo to Exenatide |
|---|---|---|---|---|
| Suicidal ideationPsychiatric disorders | 0/59 | 0/23 | 1/50 | 1/22 |
| Irritable bowel syndromeGastrointestinal disorders | 0/59 | 1/23 | 0/50 | 0/22 |
| GastritisGastrointestinal disorders | 0/59 | 0/23 | 1/50 | 0/22 |
| CellulitisInfections and infestations | 0/59 | 0/23 | 1/50 | 0/22 |
| PneumoniaInfections and infestations | 0/59 | 0/23 | 1/50 | 0/22 |
| Abscess limbInfections and infestations | 1/59 | 0/23 | 0/50 | 0/22 |
| Major depressionPsychiatric disorders | 1/59 | 0/23 | 0/50 | 0/22 |
| Event | Controlled Assessment Period - Exenatide | Controlled Assessment Period - Placebo | Extension Period - Exenatide | Extension Period - Placebo to Exenatide |
|---|---|---|---|---|
| Abdominal painGastrointestinal disorders | 2/59 | 3/23 | 1/50 | 0/22 |
| Upper respiratory tract infectionInfections and infestations | 6/59 | 0/23 | 2/50 | 0/22 |
| HyperglycaemiaMetabolism and nutrition disorders | 1/59 | 1/23 | 0/50 | 2/22 |
| CoughRespiratory, thoracic and mediastinal disorders | 4/59 | 1/23 | 0/50 | 2/22 |
| NasopharyngitisInfections and infestations | 4/59 | 2/23 | 1/50 | 1/22 |
| Urinary tract infectionInfections and infestations | 3/59 | 2/23 | 0/50 | 0/22 |
| HeadacheNervous system disorders | 4/59 | 2/23 | 2/50 | 1/22 |
| DiarrhoeaGastrointestinal disorders | 5/59 | 1/23 | 1/50 | 0/22 |
| NauseaGastrointestinal disorders | 4/59 | 1/23 | 0/50 | 1/22 |
| Abdominal pain upperGastrointestinal disorders | 3/59 | 0/23 | 1/50 | 0/22 |
Baseline analysis performed on Intent-to-Treat (ITT) Analysis Set which consisted of all randomized patients who received at least 1 dose of randomized study medication.
| Age, Continuous(years) | Exenatide | Placebo | Total |
|---|---|---|---|
| Mean | 14.9 ± 1.88 | 15.6 ± 1.66 | 15.1 ± 1.84 |
| Age, Customized(Participants) | Exenatide | Placebo | Total |
|---|---|---|---|
| < 10 | 0 | 0 | 0 |
| ≥ 10 to ≤ 12 | 8 | 3 | 11 |
| ≥ 13 to ≤ 16 | 36 | 12 | 48 |
| > 16 | 14 | 9 | 23 |
| Sex: Female, Male(Participants) | Exenatide | Placebo | Total |
|---|---|---|---|
| Female | 31 | 17 | 48 |
| Male | 27 | 7 | 34 |
| Ethnicity (NIH/OMB)(Participants) | Exenatide | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 25 | 8 | 33 |
| Not Hispanic or Latino | 29 | 13 | 42 |
| Unknown or Not Reported | 4 | 3 | 7 |
| Race/Ethnicity, Customized(Participants) | Exenatide | Placebo | Total |
|---|---|---|---|
| White | 23 | 12 | 35 |
| Black or African American | 17 | 8 | 25 |
| Asian | 2 | 1 | 3 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| American Indian or Alaska Native | 4 | 1 | 5 |
| Other | 12 | 2 | 14 |
| Region of Enrollment(Participants) | Exenatide | Placebo | Total |
|---|---|---|---|
| Bulgaria | 1 | 0 | 1 |
| Hungary | 3 | 1 | 4 |
| Israel | 4 | 3 | 7 |
| Mexico | 13 | 2 | 15 |
| United States | 35 | 17 | 52 |
| Kuwait | 2 | 1 | 3 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Supporting information: Study protocol, Sap
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