NCT02284009已完成2 期
Study 110933: Albiglutide Versus Placebo in Insulin-treated Subjects With New-onset Type 1 Diabetes Mellitus
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 33
- 主要终点
- Mean Change From Baseline in Time Normalized Stimulated (From Mixed Meal Tolerance Test [MMTT]) 2-hour Plasma C-peptide Area Under the Curve (AUC) at Week 52
研究概览
简要总结
This is a Phase II, randomized, double-blind, parallel group, placebo controlled, multicentre study of 52 weeks treatment duration. The primary objective is to evaluate the efficacy(on endogenous insulin secretion), safety and tolerability of weekly albiglutide (a glucagon-like peptide-1 receptor (GLP-1R) agonist) versus placebo when added to insulin therapy in subjects with new-onset type 1 diabetes mellitus (NOT1DM) and residual insulin production.. Approximately 68 eligible subjects will be randomised in a 3:1 ratio such that 51 subjects receive albiglutide 30 milligram (mg) once weekly (with increase to 50 mg once weekly at Week 6 if the 30-mg weekly dose is tolerated) added-on to insulin therapy and 17 subjects receive placebo once weekly added-on to insulin therapy. The total duration of a subject's participation will be approximately 72 weeks (up to 8 weeks of Screening, 52 weeks of treatment and 12 weeks of Post-treatment Follow-up)
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 30 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged 18 to 30 years, inclusive, with a diagnosis of T1DM with an interval of 28-56 days between the initial diagnosis and the first dose of study drug. Documentation of the diagnosis of T1DM (and not just insulin deficiency), including the date of diagnosis, must be obtained from the diagnosing physician.
- •Currently requires insulin for T1DM treatment, or has required insulin therapy for T1DM (for >=7 days) between the date of diagnosis and the first dose of study drug. Note: subjects currently taking twice daily commercially available pre-mixed insulin will not be eligible.
- •Positive for at least one of the following autoantibodies typically associated with T1DM: antibody to glutamic acid decarboxylase (anti-GAD) antibody to protein tyrosine phosphatase-like protein (anti-IA-2) or an insulin autoantibody (IAA). Please note: A subject who is positive for IAA and negative for the other autoantibodies will not be eligible if the subject has been using insulin for a total of >=7days.
- •Evidence of residual functioning pancreatic beta-cells as measured by a peak stimulated C-peptide level > 0.20 nanomoles/litres (nmol/L) during the Screening MMTT when plasma glucose level is >3.9 mmol/L (70 mg/dL) and <=11.1 mmol/L (200 mg/dL). Note: the Screening MMTT should not be performed within one week of resolution of a DKA event.
- •Body mass index <=32.0 kilogram/square meters (kg/m^2).
- •Female subjects of childbearing potential (i.e., not surgically sterile and/or not postmenopausal) must be practicing adequate contraception (i.e., meeting one of the criteria defined below) from at least 14 days prior to the first dose of randomised study medication until the 12-week post-treatment Follow-up visit : Abstinence from penile-vaginal intercourse, when this is the female's preferred and usual lifestyle; Oral Contraceptive, either combined or progestogen alone ; Injectable progestogen; Implants of etonogestrel or levonorgestrel; Estrogenic vaginal ring; Percutaneous contraceptive patches; Intrauterine device or intrauterine system that has a failure rate of less than 1% per year when used consistently and correctly as stated in the product label; Male partner sterilization prior to the female subject's entry into the study, and this male is the sole partner for that subject. The information on the male sterility can come from the site personnel's review of subject's medical records; medical examination of the subject and/or semen analysis; or interview with the subject on his medical history.; Male condom combined with a female diaphragm, either with or without a vaginal spermicide
- •Able and willing to provide written informed consent and to comply with all study procedures.
排除标准
- •Severe gastroparesis i.e., requiring therapy within 6 months prior to Screening
- •History of acute or chronic pancreatitis, or considered clinically at significant risk of developing pancreatitis, during the course of the study (e.g. due to symptomatic gallstones, excess alcohol use).
- •History of significant gastrointestinal surgery that in the opinion of the investigator is likely to significantly affect upper gastrointestinal or pancreatic function (e.g. gastric bypass and banding, antrectomy, Roux-en-Y bypass, gastric vagotomy, small bowel resection, or surgeries thought to significantly affect upper gastrointestinal function)
- •Personal history or family history of thyroid medullary carcinoma or multiple endocrine neoplasia type 2 (MEN2)
- •History of cancer that has not been in full remission for at least 3 years before Screening. (A history of squamous cell or basal cell carcinoma of the skin, or treated cervical intraepithelial neoplasia I or cervical intraepithelial neoplasia II is allowed)
- •Fasting triglyceride level >750 milligram/decilitre (mg/dL) at Screening. Subjects may be re-tested once during screening, and if the value no longer meets the exclusion criterion, the subject can be randomly assigned to treatment
- •Estimated Glomerular Filtration Rate (eGFR) <=30 mL/min/1.73 m^2 (calculated using the Modification of Diet in Renal Disease (MDRD) formula
- •Haemoglobinopathy that may affect proper interpretation of HbA1c
- •Alanine aminotransferase (ALT) >2.5 × upper limit of normal (ULN) and bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
- •Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). [Chronic stable hepatitis B and C are acceptable if subject otherwise meets entry criteria and are not on active antiviral treatment (e.g., presence of hepatitis B surface antigen or positive hepatitis C test result within 3 months of screening)]
- •Any clinically significant co-morbidity or abnormality (including psychiatric disorder, any other autoimmune endocrinopathy e.g., primary autoimmune hypothyroidism, hyperadrenalism, coeliac disease etc) that in the opinion of the Investigator, may pose additional risk in administering study medication or trial participation
- •Female subject is pregnant (confirmed by laboratory testing) or lactating
- •Known allergy to any GLP-1 analogue, insulin, or excipients of albiglutide
- •Treatment with any oral anti-diabetic medication within the prior 30 days or 5 half lives of that medication, whichever is longer.
- •Use of immunosuppressants, intravenous immunoglobulin, oral or systemically injected glucocorticoids within the 3 months before randomisation or high likelihood of a requirement for prolonged treatment (>1 week) in the year following randomisation. However, short courses of oral steroids (single dose or multiple doses for up to 7 days) may be permitted provided these cases are discussed with the medical monitor. Inhaled, intra-articular, and small quantities of non-potent topical corticosteroids are allowed
- •Receipt of any investigational drug within the 30 days or 5 half-lives, whichever is longer, before Screening, a history of receipt of an investigational anti-diabetic drug within the 3 months before randomisation, or receipt of albiglutide in previous studies.
结局指标
主要结局
Mean Change From Baseline in Time Normalized Stimulated (From Mixed Meal Tolerance Test [MMTT]) 2-hour Plasma C-peptide Area Under the Curve (AUC) at Week 52
时间窗: Baseline and Week 52
Participants (parts) had a balanced diet consistent with dietitian's advice and made no major changes in exercise regimens. Evening before the MMTT, participants had a full meal then fasted from 9 post meridiem (pm) until MMTT was completed. Water, black coffee or tea without sugar or artificial sweeteners was allowed. Plasma glucose was measured prior to the finger-stick test and MMTT was performed only if in range \> 3.9 millimoles per liter (mmol/L) \[70 mg/deciliter (dL)\] and \<= 11.1 mmol/L (200 mg/dL). Baseline was defined as the last non-missing value with assessment date on or before the 1st day of study medication. Change from Baseline was calculated by subtracting Baseline value from Week 52 value. Intent-to-treat (ITT) Population comprised of all randomly assigned participants who received at least 1 dose of study medication with at least 1 post-Baseline assessment of the primary endpoint.
次要结局
- Mean Change From Baseline in Time Normalized Stimulated (From MMTT) 2 Hour Plasma C-peptide AUC at Week 16, 28 and Week 64(Baseline and Weeks 16, 28 and 64)
- Maximum Stimulated Plasma C-peptide (MMTT) at Baseline, Week 16, 28, 52 and 64(Baseline and Weeks 16, 28, 52 and 64)
- Mean Change From Baseline in Time Normalized Plasma Glucagon AUC (From MMTT) at Week 16, 28, 52 and 64(Baseline and Weeks 16, 28, 52 and 64)
- Percentage of Responders at Baseline, Weeks 4, 8, 16, 28, 40, 52 and 64(Baseline and Weeks 4, 8, 16, 28, 40, 52 and 64)
- Percentage of Participants Achieving Partial Remission Status (Insulin Dose-adjusted Hemoglobin A1c (IDAA1C)<= 9.0) at Baseline, Week 4, 8, 16, 28, 40, 52 and 64(Baseline and Weeks 4, 8, 16, 28, 40, 52 and 64)
- Percent HbA1c Over Time (at Weeks 4, 8, 16, 28, 40, 52 and 64)(Weeks 4, 8, 16, 28, 40, 52 and 64)
- Change From Baseline in Mean Daily Insulin Use at Week 4, 8, 16, 28, 40, 52 and 64(Baseline and Weeks 4, 8, 16, 28, 40, 52 and 64)
- Number of Events of Participant-reported Significant Hypoglycemia, Occurring > Week 24 and <= Week 52(Week 24 to 52)
- Change From Baseline in Percent HbA1c at Week 52(Baseline and Week 52)
- Number of Hyperglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52(Baseline and Weeks 28 and 52)
- Greatest Magnitude of Hyperglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52(Baseline and weeks 28 and 52)
- Time Spent With Plasma Glucose Level <= 3.9, > 3.9 to <= 10.0, and > 10.0 Measured by 72 Hour Continuous Glucose Monitoring (CGM) at Baseline, Week 28 and 52(Baseline and Weeks 28 and 52)
- Number of Hypoglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52(Baseline and Weeks 28 and 52)
- Greatest Magnitude of Hypoglycemic Excursions for Each Participant From 7-Point Glucose Profile at Baseline, Week 28 and 52(Baseline and Weeks 28 and 52)
- Population Estimates of PK Parameters: First-order Absorption Rate Constant [Ka](48 hours after the most recent dose at Week 4, 6, 8 and 16)
- Change From Baseline in Body Weight (Kilograms) at Week 52(Baseline and Week 52)
- Population Estimates of Pharmacokinetic (PK) Parameters: Apparent Clearance [CL/F](48 hours after the most recent dose at Week 4, 6, 8 and 16)
- Weight Over Time (at Weeks 2, 4, 6, 8, 16, 28, 40, 52 and 64)(Weeks 2, 4, 6, 8, 16, 28, 40, 52 and 64)
- Population Estimates of PK Parameters: Apparent Volume of Distribution [V/F](48 hours after the most recent dose at Week 4, 6, 8 and 16)
研究者
研究点 (33)
Loading locations...
相似试验
撤回
3 期
Albiglutide Versus Placebo Added-on to Basal-Bolus Insulin Therapy in Subjects With Type 2 Diabetes MellitusDiabetes Mellitus, Type 2NCT02229240GlaxoSmithKline
进行中（未招募）
1 期
Albiglutide versus Placebo in New-Onset Type 1 Diabetes MellitusMedDRA version: 17.0Level: LLTClassification code 10012594Term: DiabetesSystem Organ Class: 100000004861Type 1 diabetes mellitusEUCTR2014-001825-33-ITGlaxoSmithKline Research & Development Ltd68
进行中（未招募）
1 期
Albiglutide versus Placebo in New-Onset Type 1 Diabetes MellitusType 1 diabetes mellitusEUCTR2014-001825-33-DEGlaxoSmithKline Research & Development Ltd68
进行中（未招募）
1 期
Albiglutide versus Placebo in New-Onset Type 1 Diabetes MellitusType 1 diabetes mellitusEUCTR2014-001825-33-GBGlaxoSmithKline Research & Development Ltd67
已完成
3 期
Safety and Efficacy of Albiglutide + Insulin Glargine Versus Insulin Lispro + Insulin Glargine Subjects With Type 2 Diabetes MellitusDiabetes Mellitus, Type 2NCT02229227GlaxoSmithKline814