CTRI/2010/091/000078已完成3 期
A PHASE III, RANDOMIZED, DOUBLE-BLIND,PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THESAFETY AND EFFICACY OF DUTOGLIPTIN IN PATIENTS WITH TYPE 2 DIABETES MELLITUS ON BACKGROUND TREATMENT WITH GLIMEPIRIDE WITH OR WITHOUT METFORMIN
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 650
- 试验地点
- 21
- 主要终点
- HbA1c
研究概览
简要总结
Approximately 168 patients will be randomized from 21 sites from India.The anticipated first patient enrollment from India is 15 Feb 2010. This will be a multicenter, randomized, double-blind, placebo-controlled, parallel-group study with a screening period of up to 8-weeks, a 4-week single-blind placebo run-in period, and a 26-week double-blind treatment period. Patients will be screened, complete the 4-week single-blind placebo run-in period, and then be randomized to dutogliptin 400 mg once daily or placebo (1:1). Randomization will be stratified by whether or not the patient is receiving metformin as part of the background therapy. During the study, all patients will be receiving background therapy with glimepiride with or without metformin. The investigational product (IP), dutogliptin 400 mg, or placebo will be administered orally once daily with or without food. Dietary and exercise advice will be provided to the patients. Glucose monitoring at home will be required; results will be used for safety monitoring but not for assessing efficacy. Efficacy analyses will be performed based on the ITT Population. The primary efficacy parameter is the change from baseline in HbA1c at Visit 8 (last observation carried forward [LOCF]). Between?treatment group differences for this parameter will be analyzed using an analysis-of-covariance (ANCOVA) model with treatment group, background therapy with oral hypoglycemic agents (OHA) (glimepiride alone vs glimepiride plus metformin), and country as factors and baseline HbA1c as a covariate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 85.00 Year(s)（—）
- 性别
- All
入选标准
- •Age 18 to 85 Inclusion Criteria To be eligible to participate in the study, patients must meet the following criteria:
- •Be able to understand and provide written informed consent before the conduct of any study-related procedures
- •Be male or female outpatients 18 to 85 years of age, inclusive, at the Screening Visit (Visit 1)
- •Be diagnosed with T2DM at least 3 months before the Screening Visit (Visit 1).Verification of T2DM diagnosis should be made by obtaining documentation or written confirmation from the physician treating the patient?s diabetes.
- •Have a body mass index of 20 to 48 kg/m2 at the Screening Visit (Visit 1)
- •Have received a stable dosage of glimepiride 4 to 6 mg/d alone or in combination with a stable dosage of metformin ≥ 1500 mg/d (or maximally tolerated dose) for at least 6 weeks before the Screening Visit (Visit 1).
- •(Note: If the patient is taking < 1500 mg/d of metformin because of intolerance, the reason for intolerance must be documented.
- •If the patient is taking > 6 mg/d of glimepiride, the dosage should be reduced to 6 mg/d at the Screening Visit [Visit 1]) OR Be willing to switch to glimepiride if receiving a stable dose that is at least half the maximal labeled dose of another SU alone or in combination with a stable dosage of metformin ≥ 1500 mg/d (or maximally tolerated dose) for at least 6 weeks before the Screening Visit (Visit 1).
- •See Appendix III and Section 9.4.7.1 for the recommended switch algorithm OR Be willing to switch to glimepiride if receiving a stable dose of any OHA other than an SU as monotherapy at the time of the screening visit ( Viisit 1): ?Stable dose of pioglitazone or rosiglitazone means a minimum of 12 weeks.
- •?Stable dose of any other OHA as monotherapy means a minimum of 6 weeks OR Be drug treatment naïve, meaning never having received an OHA or parenteral medication ( insulin or GLP-1 analogue), or if having received an OHA or parenteral medication, been off said OHA or parenteral medication fro a minimum of 6 weeks (12 weeks for pioglitazone or rosiglitazone) before screening visit ( Visit1)
- •Have received a stable dosage of glimepiride 4 to 6 mg/d alone or in combination with a stable dosage of metformin ≥ 1500 mg/d (or maximally tolerated dose) for at least 2 weeks by Visit
- •Have an HbA1c value of ≥ 7% and ≤ 10% at the Screening Visit (Visit 1), except for (1) patients who have been taking glimepiride 4 mg/d alone or in combination with metformin and (2) patients who have been taking half the maximal dose of another SU alone or in combination with metformin, in which cases HbA1c can be ≥ 7% to ≤ 10.5%.
- •These patients must be willing to switch to glimepiride and uptitrate the glimepiride dose if necessary.
- •See Appendix III for further details on HbA1c levels and glimepiride dose modification
- •Have an HbA1c value of ≥ 7% and ≤ 10% at Visit 4 (value taken at Visit 3)
- •Have an FPG ≤ 270 mg/dL (15 mmol/L) before Visit 2 for patients whose dose of glimepiride is being modified, or who are being switched to glimepiride, during the Screening period.
- •See Appendix III and Section 9.5.1.1 for further details
- •Have a fasting plasma C-peptide > 0.26 nmol/L (> 0.8 ng/mL; > 260 pmol/L) at the Screening Visit (Visit 1)
- •If taking a medication(s), other than an antidiabetic, that might affect blood glucose, must have been receiving a stable dose for at least 4 weeks before the Screening Visit (Visit 1)
- •Be willing at the Screening Visit (Visit 1) to discontinue for the duration of the study all herbal medication taken for the treatment of diabetes
- •Have a thyroid-stimulating hormone level from the Screening Visit (Visit 1) that is within normal limits.
- •If the patient is taking thyroid hormone, the dose must have been stable for at least 6 weeks before the Screening Visit (Visit 1)
- •If taking a medication(s) for hypertension (including a diuretic), must have been taking a stable dose for at least 4 weeks before the Screening Visit (Visit 1)
- •If female, must not be pregnant, not planning to become pregnant during the course of the study, and not lactating.
- •Women of childbearing potential must have a negative serum β-hCG pregnancy test at the Screening Visit (Visit 1)
- •If of childbearing potential,(or having partner(s)of child bearing potential), must be willing to use adequate contraception and not become pregnant (or have partner[s] become pregnant) during the full course of the study.
- •Adequate contraceptive measures include and are not limited to oral contraceptives (stable use for 2 or more cycles before screening); intrauterine devices; Depo-Provera; Norplant System implants; bilateral tubal ligation; vasectomy; condom or diaphragm plus either contraceptive sponge, foam, or jelly; and abstinence
- •Be willing to return for all clinic visits and complete all study-related procedures, including self-monitoring of blood glucose
- •Have a fasting plasma glucose ≤ 270 mg/dL (15 mmol/L) at Visit 4 (value taken at Visit 3).
- •A test may be repeated once if the initial value is felt to be inaccurate or unrepresentative of the patient?s usual value
- •Be willing to refrain from donating blood during the study and for up to 1 month after completing the study.
排除标准
- •Patients who meet any of the following criteria will not be eligible to participate in thestudy:
- •Currently taking more than two oral hypoglycemic agents (OHA)
- •Have been treated with insulin or a GLP-1 analogue or a DPP4 inhibitor as an outpatient within 6 weeks of the Screening Visit (Visit 1)
- •Have type 1 diabetes mellitus, maturity-onset diabetes of the young, insulin-requiring T2DM, other unusual or rare forms of diabetes mellitus, or history of diabetic ketoacidosis
- •Have elevated blood glucose due to medical treatment or to a concurrent medical condition other than T2DM (eg, hyperadrenocorticalism due to Cushing syndrome [or Cushing disease], pheochromocytoma, acromegaly, hyperthyroidism, other endocrinedisorder that can raise blood glucose)
- •Have skin lesions (eg, discoloration, swelling, atrophy, ulceration), edema states or diabetic foot ulcers considered medically important by the Investigator.
- •Have a history of epilepsy, not including childhood febrile seizures
- •Have a history of hypoglycemic episode requiring glucose, glucagon, orange juice, etc administered by a second person during the 6 months before the Screening Visit(Visit 1)
- •Have a history of hyperosmolar, hyperglycemic, or nonketotic syndrome during the6 months before Screening Visit (Visit 1)
- •Have had a stroke, myocardial infarction, symptomatic coronary artery disease, angina, or arrhythmia within 4 weeks before the Screening Visit (Visit 1) or a history of congestive heart failure class III or class IV (according to the New York Heart Association functional classification system)
- •Have a history of or risk factors for acute pancreatitis (eg, alcohol abuse,extreme hypertriglyceridemia[>100mg/dL],multiple small gallstones) or exacerbation of chronic pancreatitis
- •Have a systolic blood pressure (SBP) ≥ 160 mm Hg or < 90 mm Hg and/or diastolic blood pressure (DBP) ≥ 100 mm Hg or < 50 mm Hg at the Screening Visit (Visit 1).
- •Have had gastrointestinal surgery for obesity (including bypass, gastroplasty, and banding procedures) within the year before the Screening Visit (Visit 1) or have plans to have such surgery or procedures for the removal of excess fatty tissue (eg, liposuction or breast reduction) during the course of the study
- •Have started a weight-loss regimen within 4 weeks of the Screening Visit (Visit 1) either on one?s own or by participating in a commercial behavior modification/diet program (eg, Jenny Craig, Weight Watchers) or by taking a medication for weight reduction (eg, phentermine, sibutramine, Xenical/Alli [orlistat])
- •Be currently taking an antipsychotic medication (except prochlorperazine as needed for nausea), have taken systemic glucocorticoids at a dose greater than 5 mg of prednisone or equivalent daily within the 2 weeks before the Screening Visit (Visit 1), or be currently taking products intended to stimulate appetite (eg, megestrol acetate [Megace]).
- •See the Study Reference Manual for prednisone equivalence of other glucocorticoids
- •Have a history of cancer other than treated basal-cell or squamous-cell carcinoma of the skin.
- •(Note: Patients with a history of cancer are allowed provided the malignancy has been in complete remission for at least 5 years before the Screening Visit [Visit 1].
- •A complete remission is defined as the disappearance of all signs of cancer in response to treatment)
- •Have been infected with or have serologic evidence of previous infection with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus (as determined by the central laboratory)
- •Have total bilirubin above the upper limit of normal (ULN) (unless associated with an elevated indirect bilirubin typical of Gilbert syndrome), aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times the ULN, or alkaline phosphatase > 1.5 times the ULN from the Screening Visit (Visit 1) clinical laboratory results
- •Have hemoglobin of < 11 g/dL (< 110 g/L) from the Screening Visit (Visit 1) clinicallaboratory results
- •Have an estimated glomerular filtration rate (GFR)<50 mL/min/1.73 m2 per the Modification of Diet in Rental Disease ( MDRD) equation at screening Visit (Visit1),as provided by the central loboratory
- •Have received treatment with any investigational product (IP) or participated inany investigational study within 30 days or 5 half-lives of the IP, whichever is longer,before the Screening Visit (Visit 1)
- •Have been randomized in a previous investigational study of dutogliptin
- •Be an employee or a relative of an employee of the study center
- •Have a history of hypersensitivity reaction to glimepiride, other SU agents,metformin, pioglitazone, or DPP4 inhibitors25.
结局指标
主要结局
HbA1c
时间窗: The primary efficacy | parameter is the change from baseline in HbA1c at Visit 8
次要结局
- Fasting plasma glucose (FPG)(Change from baseline in FPG till Visit 8.)
研究者
研究点 (21)
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