Multicenter, Randomized, Double Blind, Three-arm Parallel Group Study to Evaluate Efficacy and Safety of Alogliptin and Pioglitazone Combination Therapy on Glucose Control in Type 2 Diabetes Subjects Who Have Inadequate Control With Metformin Monotherapy in Korea
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 216
- 试验地点
- 1
- 主要终点
- Change in glycohemoglobin(HbA1c) from baseline
研究概览
简要总结
This study evaluate the efficacy and safety of alogliptin and pioglitazone combination therapy in comparison with either alogliptin or pioglitazone on glucose control in the metformin-treated type 2 diabetic patients in Korea.
详细描述
Pathophysiology of type 2 diabetes is known as insulin resistance and progressive beta cell dysfunction.
Combination therapy with biguanides, glucagon-like peptide-1(GLP-1) agonists or dipeptidyl peptidase-4 inhibitor(DPP4I) and thiazolidinediones(TZD) seems reasonable theoretically, for their effects on different pathophysiologic defects.
Current treatment guidelines recommend a stepwise approach starting with lifestyle modification or lifestyle modification + metformin monotherapy, with recent focusing on patient individualization.
In Korea, Korean Diabetes Association also recommends stepwise approach and at the same time, emphasizes on the initial aggressive treatment including oral combination or insulin therapy according to HbA1c level to achieve target goal <6.5%.
Guide to the efficacy, timing, options of combination therapy is not clearly defined due to lack of sufficient evidences yet.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 19 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements
- •The subject or, when applicable, the subject's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures
- •The subjects diagnosed type 2 diabetes mellitus at least 6 months
- •Male and female and 19 to 75 years, inclusive
- •7.0% =<HbA1c =<10.0%
- •18.5 Kg/m2 =<Body Mass Index(BMI) =<45 kg/m2
- •systolic/diastolic blood pressure =<160/100 at baseline
- •hemoglobin of at least 12 g/dL for men and at least 10 g/dL for women
- •A female subject of childbearing potential who is sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from singing of informed consent throughout the duration of the study
- •Patient who receiving maximal tolerated dose of metformin at least 12 weeks without dose change (for metformin, >= 1,000 mg/day
- •fasting c-peptide greater than 0.78 ng/mL(0.26 nmol/L) at baseline
排除标准
- •The patient has received investigational compound(alogliptin or pioglitazone) within 180 days prior to baseline
- •Patient who currently taking or need to take andy medicine which may exert a significant influence on blood glucose control except metformin.
- •Severe renal disease : estimated glomerular filtration rate <50 mL/min
- •Severe liver disease or AST, ALT >= 2.5 upper limit of normal
- •Cardiac status : New York Heart Association III ~ IV
- •Hypopituitarism or adrenal insufficiency
- •Patient who has a history of major surgery, Severe infections, Severe traumas within 6 months
- •Patients who has diagnosed malignancy within 5yrs ,
- •Patients with active bladder cancer
- •Patient with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
- •Patient who has a history of hypersensitivity to Alogliptin, Pioglitazone or their ingredients
- •Pregnant or lactating woman
- •Patient who has history of excessive alcohol abuse
- •Subject who is involved in other clinical trial within 90 days prior to initiation of this study.
- •Subject who the investigator deems inappropriate to participate in this study
研究组 & 干预措施
alogliptin + pioglitazone
alogliptin 25 mg 1 tablet daily for 24 weeks pioglitazone 30 mg 1 tablet daily for 24 weeks metformin for 24 weeks as the same dose and frequency as before enroll
干预措施: alogliptin + pioglitazone (Drug)
alogliptin
alogliptin 25 mg 1 tablet daily for 24 weeks pioglitazone matching placebo 1 tablet daily for 24 weeks metformin for 24 weeks as the same dose and frequency as before enroll
干预措施: alogliptin (Drug)
Pioglitazone
alogliptin matching placebo 1 tablet daily for 24 weeks pioglitazone 30 mg 1 tablet daily for 24 weeks metformin for 24 weeks as the same dose and frequency as before enroll
干预措施: Pioglitazone (Drug)
结局指标
主要结局
Change in glycohemoglobin(HbA1c) from baseline
时间窗: baseline, 24 weeks
次要结局
- Proportion of subjects achieving HbA1c <6.5%(24 week)
- Change in GA/HbA1c ratio from baseline(baseline, 12 weeks)
- Change in HbA1c from baseline(12 week)
- Proportion of subjects achieving HbA1c < 7.0%(24 week)
- Change in fasting blood sugar from baseline(baseline, 12 weeks)
- Change in total cholesterol from baseline(baseline, 12 weeks)
- Changes in glycated albumin(GA) from baseline(baseline, 12 weeks)
- Incidence of hyperglycemic rescue(12 week)
- Change in triglycerides from baseline(baseline, 12 weeks)
- Change in LDL-cholesterol from baseline(baseline, 12 weeks)
- Change in HDL-cholesterol from baseline(baseline, 12 weeks)
- Change in Homeostasis Model Assessment-Insulin resistance(HOMA-IR) from baseline(baseline, 24 weeks)
- Change in Homeostasis Model Assessment - beta cell (HOMA-beta) from baseline(baseline, 24 weeks)
- The number of serious adverse events(upto 24 weeks)
- Change in highly sensitive C reactive protein(hs-CRP) from baseline(baseline, 24 weeks)
- Change in Plasmonogen activator inhibitor-1(PAI-1) from baseline(baseline, 24 weeks)
- The number of subject with any abnormality of laboratory evaluation(24 week)
- Change in B-type natriuretic pepetide(BNP) from baseline(baseline, 24 weeks)
- event rate of hypoglycemia(upto 24 weeks)
- No of subject with adverse event of special interest(upto 24 weeks)
- The number of subject with hypersensitivity to study drugs(upto 24 weeks)
- The number of subject with any change of findings in Chest X-ray from baseline(24 week)
- The number of subject with any change of findings in electrocardiogram from baseline(24 week)
研究者
Kun-Ho Yoon
Professor
The Catholic University of Korea