Clinical trial NCT02231021: The Practical Evidence of Antidiabetic Combination Therapy in Korea
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Keywords: Diabetes Mellitus, Type 2
alogliptin
pioglitazone
DPP4 inhibitor
thiazolidinedione
Lead sponsor: The Catholic University of Korea
Sponsor class: OTHER
Collaborators: name: Takeda
First posted: 2014-09-03
Enrollment: 216
Sex: ALL
Minimum age (years): 19
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

There is no clear report to demonstrate the clinical benefit of initial TZD and DPP4I combination therapy in the Korean.

Thus it is reasonable to study the effect of combination therapy in the patients with sub-optimal glucose control with metformin therapy only, comparing various combination options metformin with DPP4I only, TZD only, or both.

The hypothesis of this study is that combination therapy of alogliptin and pioglitazone added on the metformin has superior effect on HbA1c reduction than metformin and either alogliptin or pioglitazone in 6 month treatment.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change in glycohemoglobin(HbA1c) from baseline
timeFrame: baseline, 24 weeks
Secondary outcomes:
measure: Proportion of subjects achieving HbA1c < 7.0%
timeFrame: 24 week
measure: Proportion of subjects achieving HbA1c <6.5%
timeFrame: 24 week
measure: Changes in glycated albumin(GA) from baseline
timeFrame: baseline, 24 weeks
measure: Change in GA/HbA1c ratio from baseline
timeFrame: baseline, 24 weeks
measure: Change in fasting blood sugar from baseline
timeFrame: baseline, 24 weeks
measure: Incidence of hyperglycemic rescue
timeFrame: 12 week
measure: Change in HbA1c from baseline
timeFrame: 12 week
measure: Change in total cholesterol from baseline
timeFrame: baseline, 24 weeks
measure: Change in triglycerides from baseline
timeFrame: baseline, 24 weeks
measure: Change in LDL-cholesterol from baseline
timeFrame: baseline, 24 weeks
measure: Change in HDL-cholesterol from baseline
timeFrame: baseline, 24 weeks
measure: Changes in glycated albumin(GA) from baseline
timeFrame: baseline, 12 weeks
measure: Change in GA/HbA1c ratio from baseline
timeFrame: baseline, 12 weeks
measure: Change in fasting blood sugar from baseline
timeFrame: baseline, 12 weeks
measure: Change in total cholesterol from baseline
timeFrame: baseline, 12 weeks
measure: Change in triglycerides from baseline
timeFrame: baseline, 12 weeks
measure: Change in LDL-cholesterol from baseline
timeFrame: baseline, 12 weeks
measure: Change in HDL-cholesterol from baseline
timeFrame: baseline, 12 weeks
measure: Change in Homeostasis Model Assessment-Insulin resistance(HOMA-IR) from baseline
timeFrame: baseline, 24 weeks
measure: Change in Homeostasis Model Assessment - beta cell (HOMA-beta) from baseline
timeFrame: baseline, 24 weeks
measure: Change in highly sensitive C reactive protein(hs-CRP) from baseline
timeFrame: baseline, 24 weeks
measure: Change in Plasmonogen activator inhibitor-1(PAI-1) from baseline
timeFrame: baseline, 24 weeks
measure: Change in B-type natriuretic pepetide(BNP) from baseline
timeFrame: baseline, 24 weeks
measure: event rate of hypoglycemia
timeFrame: upto 24 weeks
measure: No of subject with adverse event of special interest
timeFrame: upto 24 weeks
measure: The number of serious adverse events
timeFrame: upto 24 weeks
measure: The number of subject with hypersensitivity to study drugs
timeFrame: upto 24 weeks
measure: The number of subject with any abnormality of laboratory evaluation
timeFrame: 12 week
measure: The number of subject with any abnormality of laboratory evaluation
timeFrame: 24 week
measure: The number of subject with any change of findings in Chest X-ray from baseline
timeFrame: 24 week
measure: The number of subject with any change of findings in electrocardiogram from baseline
timeFrame: 24 week
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul St Mary's Hospital, The Catholic University of Korea
Study officials:
affiliation: Seoul St Mary's Hospital, The Catholic Univerisity of Korea
name: Kun-Ho Yoon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: