The Practical Evidence of Antidiabetic Combination Therapy in Korea

NCT ID: NCT02231021

Last Updated: 2019-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 216 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2019-01-28

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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

alogliptin + pioglitazone

Intervention Type: DRUG

alogliptin 25 mg and pioglitazone 30 mg add-on background medication metformin

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

Group Type: ACTIVE_COMPARATOR

alogliptin

Intervention Type: DRUG

alogliptin 25 mg add-on background medication metformin

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

Group Type: ACTIVE_COMPARATOR

Pioglitazone

Intervention Type: DRUG

pioglitazone 30 mg add-on background medication metformin

Interventions

alogliptin

alogliptin 25 mg add-on background medication metformin

Intervention Type: DRUG

Pioglitazone

pioglitazone 30 mg add-on background medication metformin

Intervention Type: DRUG

alogliptin + pioglitazone

alogliptin 25 mg and pioglitazone 30 mg add-on background medication metformin

Intervention Type: DRUG

Other Intervention Names

Nesina; actos; Nesina; Actos

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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: collaborator

Kun-Ho Yoon

OTHER

Sponsor Role: lead

Responsible Party

Kun-Ho Yoon

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Kun-Ho Yoon, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Seoul St Mary's Hospital, The Catholic Univerisity of Korea

Locations

Seoul St Mary's Hospital, The Catholic University of Korea

Seoul, , South Korea

Countries

South Korea

Other Identifiers

ALO-IIT-012

Identifier Type: -

Identifier Source: org_study_id