A randomised, double-blind, placebo-controlled, 3 parallel group efficacy and safety study of linagliptin 2.5 mg twice daily versus 5 mg once daily over 12 weeks as add-on therapy to a twice daily dosing regimen of metformin in patients with type 2 diabetes mellitus and insufficient glycaemic control
试验速览
- 阶段
- 2 期
- 入组人数
- 451
- 试验地点
- 5
- 主要终点
- change in HbA1c from baseline
研究概览
简要总结
This is a global trial (France, Morrocco, Italy, Spain, Belgium, Canada, Republic of Korea, Malaysia, India, Netherlands) with Indian traget for 80 patient recruitment. Anticipated first date of enrollement in India is 7 Dec 2009. This randomised, double-blind, multi-national, and placebo-controlled, three parallel groups study will compare linagliptin 2.5 mg twice daily versus 5 mg once daily as add-on to a background therapy of metformin. In total, 451 patients with type 2 diabetes who meet the entry criteria are planned for inclusion in this trial. The randomised treatment will be double-blind within the dose groups of linagliptin (i.e., each patient will receive one active treatment and one placebo to match the alternative active treatment) and placebo (i.e., each patient will receive placebos to match each of the active treatments). Patients with previous oral antidiabetic therapy (e.g., sulphonylureas, meglitinides, DPP-4 inhibitors, α-glucosidase inhibitors) will stop this current antidiabetic therapy (background therapy of metformin will continue) and enter a six-week wash-out phase (4 weeks, followed by a two week open-label placebo run-in phase). Patients pre-treated with metformin alone will undergo a 2-week open-label placebo run-in phase before randomisation. Patients who successfully complete the placebo run-in phase and who still meet the inclusion/exclusion criteria will be randomised to the 12-week treatment phase of the study in which they will receive either 1 of the 2 doses of linagliptin or placebo in addition to background therapy of metformin.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant, Investigator and Outcome Assessor Blinded
入排标准
入选标准
- •Diagnosis of type 2 diabetes mellitus prior to informed consent.
- •Male and female patients, currently treated with metformin alone, or with metformin and not more than one other oral antidiabetic drug (antidiabetic therapy may be a sulphonylurea, meglitinide, DPP-4 inhibitor or α-glucosidase inhibitor and its dose has to be unchanged for 12 weeks prior to informed consent).A total daily dose of ≥1500 mg/day metformin divided into twice daily administration (e.g., 850 mg bid, 1000 mg bid, 850/1000 mg bid or 500/1000 mg bid) is required for inclusion into the trial.
- •A patient taking metformin tid can be included if switched to a bid dosing regimen at the time of informed consent.
- •In this case, the total daily dose must be maintained (e.g., 500 mg tid to 1000/500 mg bid, 1000/500/500 mg tid to 1000 bid, 500/500/850 mg tid to 1000/850 mg bid).
- •Patients treated with a total daily dose of metformin of less than 1500 mg (e.g., 500 mg bid) can be included in the trial only if the Investigator has documented that the dose is the maximum tolerated dose for that patient.The total daily dosage of metformin needs to be stable for at least 12 weeks prior to randomisation and throughout the duration of the study.
- •Glycosylated haemoglobin A1 (HbA1c) at Visit 1a (Screening) fulfils the followingcriteria:- For patients undergoing wash out of previous medication: ≥7.0 % to ≤9.5 %..- For patients not undergoing wash-out of previous medication: ≥7.0% to ≤10.0%.
- •Glycosylated haemoglobin A1 (HbA1c) ≥7.0 to ≤10.0% at Visit 2 (Start of Run-in).
- •Age ≥18 and ≤80 years at Visit 1a (Screening).
- •BMI ≤45 kg/m2 (Body Mass Index) at Visit 1a (Screening).
- •Signed and dated written informed consent by date of Visit 1a in accordance withGCP and local legislation.
排除标准
- •Treatment with extended release formulations of metformin within 12 weeks prior to consent.
- •Uncontrolled hyperglycaemia with a glucose level 240 mg/dL (13.3 mmol/L) after an overnight fast during wash-out/placebo run-in and confirmed by a second measurement (not on the same day).
- •Myocardial infarction, stroke or TIA within 6 months prior to informed consent.
- •Impaired hepatic function, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined at Visit 1a.
- •Gastric bypass surgery.
- •Known hypersensitivity or allergy to the investigational product or its excipients or to the trial background therapy (i.e., metformin).
- •Contraindication to metformin therapy according to local label, for example: ?
- •Renal disease or renal dysfunction (e.g., as specified by product information of locally approved metformin) ?
- •Dehydration by clinical judgement of the investigator ?
- •Acute or chronic metabolic acidosis (present condition in patient history) ?
- •Hereditary galactose intolerance.
- •Renal failure or renal impairment (serum creatinine ≥1.5 mg/dL [132 μmol/L]) as determined at Visit 1a (Screening).
- •Treatment with rosiglitazone, pioglitazone, GLP-1 analogues/mimetics or insulin within 3 months prior to informed consent.
- •Treatment with anti-obesity drugs (e.g., sibutramine, orlistat, rimonabant) 3 months prior to informed consent.
- •Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation.
- •Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent.
- •However, the use of inhaled steroids (e.g., for asthma, COPD) is not an exclusion as these do not cause systemic steroid action.
- •Participation in another trial with an investigational drug within 2 months prior to informed consent.
- •are nursing or pregnant or ?
- •are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial.
- •Acceptable methods of birth control include transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence and vasectomised partner.
- •No exception will be made.
结局指标
主要结局
change in HbA1c from baseline
时间窗: 6 week and 12 week (visit 4 & 5)
次要结局
- ? Occurrence of relative efficacy response (HbA1c lowering by at least 0.5% after 12 weeks of treatment)(? Change from baseline in HbA1c by visit over time)