A Phase 3, Double-Blind, Placebo-Controlled, Randomized, Multi-Center Study to Assess the Safety and Efficacy of Exenatide Once Weekly in Adolescents With Type 2 Diabetes
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period)
研究概览
简要总结
The study examines the Safety and efficacy study of exenatide once weekly in children and adolescents with type 2 diabetes
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 10 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
EQW
Exenatide once weekly
干预措施: Exenatide Once Weekly (Drug)
Placebo
Placebo once weekly
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period)
时间窗: Day 1 (Week 0) up to Week 24, plus up to a maximum of 90 days follow up
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.
Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) to Week 24 (Controlled Assessment Period)
时间窗: Baseline (Week 0) and Week 24
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 of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24
时间窗: Samples were collected on Day 1 (Week 0), Week 4, Week 8, Week 12 and 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.
次要结局
- Change From Baseline in Fasting Plasma Glucose (FPG) Concentration to Week 24 (Controlled Assessment Period)(Baseline (Week 0) and Week 24)
- Change From Baseline in Body Weight to Week 24 (Controlled Assessment Period)(Baseline (Week 0) and Week 24)
- Change From Baseline in Blood Pressure (Systolic and Diastolic) to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)(Baseline (Week 0) and Week 52)
- Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period)(At Week 24)
- Change From Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period)(Baseline (Week 0) and Week 24)
- Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period)(At Week 4, Week 8, Week 12, Week 18 and Week 24)
- Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period)(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)(Baseline (Week 0) and Week 24)
- Change From Baseline in Fasting Insulin to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)(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)(At Week 52)
- Change From Baseline in Fasting Insulin to Week 24 (Controlled Assessment Period)(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)(Baseline (Week 0) and Week 24)
- Change From Baseline in HbA1c to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)(Baseline (Week 0) and Week 52)
- Change From Baseline in Lipids Profiles to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)(Baseline (Week 0) and Week 52)
- Plasma Exenatide Concentrations to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)(Samples were collected on Day 1 (Week 0), Week 4, Week 8, Week 12, Week 24 and Week 52)
- Change From Baseline in FPG Concentration to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)(Baseline (Week 0) and Week 52)
- Change From Baseline in Body Weight to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)(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)(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)(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)(At Week 4, Week 8, Week 12, Week 18, Week 24, Week 28, Week 40 and Week 52)