NCT02229227已完成3 期
Study 200977: Albiglutide + Insulin Glargine Versus Insulin Lispro + Insulin Glargine in the Treatment of Subjects With Type 2 Diabetes Mellitus: The Switch Study
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
- 814
- 试验地点
- 1
- 主要终点
- Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26
研究概览
简要总结
This Phase IIIb, randomized, open-label, parallel group, active control, multicenter, treat to-target study of 26 weeks' treatment duration will evaluate the efficacy and safety of once-weekly albiglutide as replacement of prandial insulin in subjects with type 2 diabetes mellitus (T2DM) failing to achieve adequate glycemic control on their current basal bolus insulin regimen (with or without metformin). Approximately 794 subjects will be randomly assigned in a 1:1 ratio to 1 of 2 treatment groups: albiglutide + insulin glargine (with insulin lispro discontinuation at Week 4) (with or without metformin) or to intensification of insulin glargine + insulin lispro (with or without metformin). The study will comprise 4 study periods : Screening (2 weeks), Standardization (4 weeks), Treatment (26 weeks), and Post treatment Follow up (4 weeks). The total duration of a subject's participation will be approximately 36 weeks.
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
- None
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
- •Male or female, 18 years of age or older (inclusive at the time of Screening) with T2DM
- •HbA1c >= 7.0% and <= 9.0% at Screening.
- •Currently treated with a basal-bolus insulin regimen (with or without metformin) for at least 3 months before Screening. The subject must be taking the following:
- •Basal insulin (1 or 2 daily injections of neutral protamine Hagedorn insulin, insulin glargine, insulin detemir, or insulin degludec) AND
- •Bolus insulin (at least 2 injections of regular insulin, insulin glulisine, insulin aspart, or insulin lispro) with a total daily dose of bolus insulin <= 70 units
- •In addition, the total daily dose of insulin must be <= 140 units
- •If taking metformin, a stable dose for at least 8 weeks before Screening Note: Subject should not have received any other antidiabetic medication within 30 days before screening (e.g., glucagon-like peptide-1 receptor (GLP-1R) agonist, dipeptidyl peptidase-IV inhibitor, SU, or thiazolidinedione). Subjects receiving commercially available premixed basal and prandial insulin are not eligible for this study.
- •Fasting C-peptide >= 0.8 nanogram (ng) per milliliter (mL) [>= 0.26 nanomoles per litre (nmol/L)]
- •Body mass index <= 40 kilogram per square meter( kg/m^2)
- •Thyroid-stimulating hormone (TSH) level is normal or clinically euthyroid as demonstrated by further thyroid tests (e.g., free T4)
- •Female subjects of childbearing potential (i.e., not surgically sterile and/or not postmenopausal) must be practicing adequate contraception (as defined in the protocol) for the duration of participation in the study including the 4-week post treatment Follow-up Period..
- •Willing and able to comply with all study procedures including performance of frequent self-monitored blood glucose (SMBG) profiles according to the protocol
- •Able and willing to provide written informed consent
排除标准
- •Type 1 diabetes mellitus
- •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 intra-epithelial neoplasia I or II is allowed)
- •Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2
- •Current symptomatic biliary disease or history of acute or chronic pancreatitis
- •Severe gastroparesis, i.e., requiring regular therapy within 6 months before Screening
- •History of significant GI surgery that in the opinion of the investigator is likely to significantly affect upper GI 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 GI function]
- •History of severe hypoglycemia unawareness
- •Diabetic complications (e.g., active proliferative retinopathy or severe diabetic neuropathy) or any other clinically significant abnormality (including a psychiatric disorder) that, in the opinion of the investigator, may pose additional risk in administering the investigational product
- •Clinically significant CV and/or cerebrovascular disease within 3 months before Screening including, but not limited to, the following:
- •Stroke or transient ischemic attack
- •Acute coronary syndrome (myocardial infarction [MI] or unstable angina not responsive to nitroglycerin)
- •Cardiac surgery or percutaneous coronary procedure
- •Current or history of heart failure (New York Heart Association class III or IV)
- •Alanine aminotransferase (ALT) >2.5 × upper limit of normal (ULN) or 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, esophageal 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 is not on active antiviral treatment [e.g., presence of hepatitis B surface antigen or positive hepatitis C test result within 3 months of Screening])
- •Hemoglobin <11 gram (g) per (dL) [<110 g/L] for male subjects and <10 g/dL (<100 g/L) for female subjects at Screening
- •Estimated glomerular filtration rate (eGFR) <= 30 millilitre per minute per 1.73 square meters (mL/min/1.73 m^2) (calculated using the Modification of Diet in Renal Disease [MDRD] formula) at Screening Note: As the use of metformin in subjects with varying degrees of renal function may differ from country to country, use of metformin should be in accordance with the metformin product label within the participating country.
- •Fasting triglyceride level >750 mg/dL at Screening
- •Hemoglobinopathy that may affect proper interpretation of HbA1c
- •Known allergy to albiglutide or any product components (including yeast and human albumin), any other GLP-1 analogue, insulin, or other study medication's excipients OR other contraindications (per the prescribing information) for the use of potential study medications (e.g., insulin glargine, insulin lispro)
- •Use of oral or systemically injected glucocorticoids within the 3 months before randomization or high likelihood of a requirement for prolonged treatment (>1 week) in the 6 months following randomization. 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, epidural, and topical corticosteroids are allowed
- •Female subject is pregnant (confirmed by laboratory testing) or lactating
- •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 antidiabetic drug within the 3 months before randomization, or receipt of albiglutide in previous studies
研究组 & 干预措施
Albiglutide + Insulin Glargine Arm
Experimental
During standardization period, subjects will transit from basal bolus regimen received during screening period to insulin glargine plus insulin lispro. During treatment period, subject will receive Albiglutide 30 milligrams (mg) weekly subcutaneous (SC) injection and insulin lispro dose will be downtitrated to half that used in the standardization period. At Week 4, Albiglutide will be uptitrated to 50 mg weekly SC injection and insulin lispro will be stopped for the remainder of the treatment Period. Insulin lispro may be re-introduced after Week 8 according to pre-defined hyperglycemia thresholds. Insulin will be adjusted according to protocol-defined insulin titration algorithms
干预措施: Albiglutide (Drug)
Insulin Glargine + Insulin Lispro Arm
Experimental
During standardization period, subjects will transit from basal bolus regimen received during screening period to insulin glargine plus insulin lispro. During treatment period, subject will continue with the same doses as at the end of the standardization period and doses will be adjusted according to protocol-defined insulin titration algorithms
干预措施: Insulin Glargine and Insulin Lispro (Drug)
结局指标
主要结局
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26
时间窗: Baseline (Day -1) and Week 26
HbA1c is glycosylated hemoglobin. It was measured at Baseline and at Week 26. The analysis was conducted using mixed-effect model with repeated measures (MMRM). The model included HbA1c change from Baseline as the dependent variable; treatment, region, age category, current metformin use, visit week, treatment-by-week interaction, and Baseline HbA1c-by-week interaction as fixed effects; Baseline HbA1c as a continuous covariate; and participant as a random effect. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value.
次要结局
- Number of Participants Who Met Prespecified Criteria for Severe, Persistent Hyperglycemia at Week 26(Week 26)
- Total Daily Insulin Dose at Week 26(Week 26)
- Number of Participants Achieving HbA1c <7.0% at Week 26(Week 26)
- Number of Participants Achieving a HbA1c <6.5% up to Week 26(Up to Week 26)
- Number of Participants Meeting Prespecified Criteria for Severe, Persistent Hyperglycemia up to Week 26(Up to Week 26)
- Number of Participants With Other AE of Special Interest(Up to Week 26)
- Number of Participants With Hypoglycemic Events (in Total and by Each Category as Defined by the American Diabetes Association Criteria)(Up to Week 26)
- Number of Participants With Hematology Values of Clinical Concern(Up to 30 weeks)
- Total Daily Bolus Insulin (Insulin Lispro) at Week 4, 10, 18, and 26 Visits(Weeks 4, 10, 18, and 26)
- Total Number of Weekly Insulin Injections to Achieve Glycemic Control at Baseline/Randomization and Week 4, 10, 18, and 26(Baseline (Day -1) and Weeks 4, 10, 18 and 26)
- Percentage of Participants Achieving HbA1c <7.0% Without Severe or Documented Symptomatic Hypoglycemia at Week 26(Week 26)
- Percentage of Participants Achieving HbA1c <7.0% Without Weight Gain and Without Severe or Documented Hypoglycemia at Week 26(Week 26)
- Number of Participants With Vital Signs of Clinical Concern(Up to 30 weeks)
- Percentage of Participants With Severe or Documented Symptomatic Hypoglycemia Through Week 26(Up to Week 26)
- Change From Baseline in Body Weight at Week 26(Baseline (Day -1) and Week 26)
- Change From Baseline to Week 26 in Body Weight(Baseline (Day -1) to Week 26)
- Change From Baseline to Week 26 in HbA1c(Baseline to Week 26)
- Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26(Baseline and Week 26)
- Number of Participants Achieving HbA1c <7.0% up to Week 26(Up to Week 26)
- Number of Participants Achieving a HbA1c <6.5% at Week 26(Week 26)
- Total Daily Insulin Dose at Week 4, Week 10 and Week 18(Weeks 4, 10, and 18)
- Percentage of Participants Achieving HbA1c <7.0% Without Weight Gain at Week 26(Week 26)
- Number of Participants With Daytime and Nocturnal Hypoglycemia(Up to Week 26)
- Number of Participants Treated With Once-weekly Albiglutide That Were Able to Discontinue Insulin Lispro at Week 4 and Did Not Meet Prespecified Criteria for Severe, Persistent Hyperglycemia Through Week 26(Up to Week 26)
- Change From Baseline to Week 26 in FPG(Baseline to Week 26)
- Number of Participants With On-therapy Adverse Events (AE) and Serious AE (SAE), and AE Leading to Discontinuation of Randomized Study Medication(Up to Week 26)
- Percentage of Participants With Events of Hypoglycemia With Confirmed Home Blood Glucose Monitoring and/or Third-party Intervention Through Week 26(Up to Week 26)
- Number of Participants With Hypoglycemia With Blood Glucose <56 Milligrams Per Deciliter (mg/dL) (<3.1 Millimoles Per Liter [mmol/L]), Regardless of Symptoms(Up to Week 26)
- Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26(Week 0 and Week 26)
- Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Parameters(Up to 30 weeks)
- Total Daily Basal Insulin (Insulin Glargine) at Week 4, 10, 18, and 26 Visits(Weeks 4, 10, 18, and 26)
- Mean Albumin at Week 0 and Week 26(Week 0 and Week 26)
- Mean Creatinine at Week 0 and Week 26(Week 0 and Week 26)
- Mean Specific Gravity at Week 0 and Week 26(Week 0 and Week 26)
- Number of Participants With Clinical Chemistry Values of Clinical Concern(Up to 30 weeks)
- Mean Urine Albumin/Creatinine Ratio at Week 0 and Week 26(Week 0 and Week 26)
- Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26(Week 0 and Week 26)
- Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26(Week 0 and Week 26)
- Change From Baseline in Total Cholesterol (TC), Low-density Lipoprotein Cholesterol (LDL-c), High Density Lipoprotein (HDL-c), Triglycerides (TG) and Free Fatty Acids (FFA) at Week 10 and Week 26(Baseline, Week 10 and Week 26)
研究者
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