NCT03021187已完成3 期
Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Insulin. A 52-week, Randomised, Double-blind, Placebo-controlled Trial (PIONEER 8 - Insulin add-on)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 731
- 试验地点
- 1
- 主要终点
- Change in HbA1c (Week 26)
研究概览
简要总结
This trial is conducted globally. The aim of the trial is to investigate the efficacy and safety of oral semaglutide versus placebo in subjects with Type 2 Diabetes Mellitus treated with insulin. All subjects should continue their pre-trial insulin therapy (basal, basal-bolus or premixed regimen including combinations of soluble insulins) throughout the trial. Subjects treated with metformin in addition to insulin treatment must continue their metformin treatment throughout the entire trial.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial. - Male or female, age above or equal to 18 years at the time of signing informed consent. For Japan only: Male or female, age above or equal to 20 years at the time of signing informed consent. - Diagnosed with type 2 diabetes mellitus 90 days or more prior to the day of screening. - HbA1c (glycosylated haemoglobin) of 7.0-9.5% (53-80 mmol/mol) (both inclusive). - Stable treatment with one of the following insulin regimens (minimum 10 IU/day) 90 or more days prior to the day of screening. Maximum 20% change in total daily dose is acceptable: (1) Basal insulin alone or (2) Basal and bolus insulin in any combination or (3) Premixed insulin including combinations of soluble insulins
排除标准
- •Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice). For Greece only: adequate contraceptive measures are defined as combined hormonal contraception (containing oestrogen and progesterone), which suppress ovulation (oral, intravaginal, percutaneous), progesterone-only hormonal contraception which suppress ovulation (oral, injectable, implantable), intrauterine device, hormone-releasing intrauterine system, bilateral tubal occlusion, partner with vasectomy, sexual abstinence. For Japan only: Adequate contraceptive measures are abstinence (not having sex), diaphragm, condom (by the partner), intrauterine device, sponge, spermicide or oral contraceptives. For Canada only: adequate contraceptive measures are defined as combined hormonal contraception (containing oestrogen and progesterone), which suppress ovulation (oral, intravaginal, percutaneous), progesterone-only hormonal contraception which suppress ovulation (oral, injectable, implantable), intrauterine device, hormone-releasing intrauterine system, bilateral tubal occlusion, partner with vasectomy, sexual abstinence - Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol. - Family or personal history of Multiple Endocrine Neoplasia Type 2 (MEN 2) or Medullary Thyroid Carcinoma (MTC). - History of pancreatitis (acute or chronic). - History of major surgical procedures involving the stomach and potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery). - Any of the following: myocardial infarction (MI), stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and randomisation. - Classified as being in New York Heart Association (NYHA) Class IV. - Planned coronary, carotid or peripheral artery revascularisation known on the day of screening. - Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) less than 60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI). - Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening. An exception is short-term change of insulin treatment for acute illness for a total of 14 days or less. - Known hypoglycaemic unawareness according to Clarke's questionnaire. - Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation. - History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ). - Subjects with alanine aminotransferase (ALT) more than 2.5 x upper normal limit (UNL).
研究组 & 干预措施
Semaglutide 3 mg
Experimental
干预措施: semaglutide (Drug)
Semaglutide 3 mg + 7 mg
Experimental
干预措施: semaglutide (Drug)
Semaglutide 3 mg + 7 mg + 14 mg
Experimental
干预措施: semaglutide (Drug)
Placebo
Placebo Comparator
干预措施: placebo (Drug)
结局指标
主要结局
Change in HbA1c (Week 26)
时间窗: Week 0, week 26
Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 26. The endpoint was evaluated based on data from the in-trial observation period. In-trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. The endpoint was also analysed based on data from the on-treatment without rescue medication observation period. On-treatment without rescue medication observation period started at the date of the first dose of trial product and includes the period after initiation of rescue medication, if any, and excludes the period after premature trial discontinuation, if any.
次要结局
- Change in Waist Circumference(Week 0, week 26, week 52)
- Change in HbA1c (Week 52)(Week 0, week 52)
- Change in Body Weight (Week 26)(Week 0, week 26)
- Change in Body Weight (kg) (Week 52)(Week 0, week 52)
- Change in Fasting Plasma Glucose (FPG)(Week 0, week 26, week 52)
- Change in Self-measured Plasma Glucose (SMPG) Mean 7-point Profile(Week 0, week 26, week 52)
- Change in SMPG Mean Postprandial Increment Over All Meals(Week 0, week 26, week 52)
- Change in Body Weight (Percentage)(Week 0, week 26, week 52)
- Change in Body Mass Index(Week 0, week 26, week 52)
- Change in Total Cholesterol - Ratio to Baseline(Week 0, week 26, week 52)
- Change in LDL Cholesterol - Ratio to Baseline(Week 0, week 26, week 52)
- Change in HDL Cholesterol - Ratio to Baseline(Week 0, week 26, week 52)
- Change in Triglycerides - Ratio to Baseline(Week 0, week 26, week 52)
- Change in Total Daily Insulin Dose(Week 0, week 26, week 52)
- Participants Who Achieve: HbA1c < 7.0% (53 mmol/Mol) (American Diabetes Association (ADA) Target) (Yes/no)(Week 26, week 52)
- Participants Who Achieve: HbA1c ≤ 6.5% (48 mmol/Mol) (AACE Target) (Yes/no)(Week 26, week 52)
- Participants Who Achieve Body Weight Loss ≥5% (Yes/no)(Week 26, week 52)
- Participants Who Achieve Body Weight Loss ≥10% (Yes/no)(Week 26, week 52)
- Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)(Week 26, week 52)
- Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no)(Week 26, week 52)
- Time to Additional Anti-diabetic Medication(Weeks 0-52)
- Time to Rescue Medication(Weeks 0-52)
- Number of Treatment-emergent Adverse Events (TEAEs) During Exposure to Trial Product(Weeks 0-57)
- Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes(Weeks 0-57)
- Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes(Weeks 0-57)
- Change in Amylase - Ratio to Baseline(Week 0, week 26, week 52)
- Change in Lipase - Ratio to Baseline(Week 0, week 26, week 52)
- Change in Pulse Rate(Week 0, week 26, week 52)
- Change in SBP and DBP(Week 0, week 26, week 52)
- Change in ECG Evaluation(Week 0, week 26, week 52)
- Change in Physical Examination(Week -2, week 52)
- Change in Eye Examination Category(Week -2, week 52)
- Semaglutide Plasma Concentrations for Population PK Analyses(Weeks 0-52)
- Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)(Week 0, week 26, week 52)
- Change in IWQoL-Lite-CT: Total Score and Scores From the 4 Domains(Week 0, week 26, week 52)
- Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed)(Week 0, week 26, week 52)
研究者
研究点 (1)
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