The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK)

February 7, 2019 updated by: Kun-Ho Yoon

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

216

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 137-701
        • Seoul St Mary's Hospital, The Catholic University of Korea

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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
Drug: alogliptin + pioglitazone
alogliptin 25 mg and pioglitazone 30 mg add-on background medication metformin
Other Names:
  • Actos
  • Nesina
ACTIVE_COMPARATOR: 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
Drug: alogliptin
alogliptin 25 mg add-on background medication metformin
Other Names:
  • Nesina
ACTIVE_COMPARATOR: 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
Drug: Pioglitazone
pioglitazone 30 mg add-on background medication metformin
Other Names:
  • actos

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in glycohemoglobin(HbA1c) from baseline
Time Frame: baseline, 24 weeks
baseline, 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of subjects achieving HbA1c < 7.0%
Time Frame: 24 week
24 week
Proportion of subjects achieving HbA1c <6.5%
Time Frame: 24 week
24 week
Changes in glycated albumin(GA) from baseline
Time Frame: baseline, 24 weeks
baseline, 24 weeks
Change in GA/HbA1c ratio from baseline
Time Frame: baseline, 24 weeks
baseline, 24 weeks
Change in fasting blood sugar from baseline
Time Frame: baseline, 24 weeks
baseline, 24 weeks
Incidence of hyperglycemic rescue
Time Frame: 12 week
at Week 12, HbA1c >9.0%
12 week
Change in HbA1c from baseline
Time Frame: 12 week
12 week
Change in total cholesterol from baseline
Time Frame: baseline, 24 weeks
baseline, 24 weeks
Change in triglycerides from baseline
Time Frame: baseline, 24 weeks
baseline, 24 weeks
Change in LDL-cholesterol from baseline
Time Frame: baseline, 24 weeks
baseline, 24 weeks
Change in HDL-cholesterol from baseline
Time Frame: baseline, 24 weeks
baseline, 24 weeks
Changes in glycated albumin(GA) from baseline
Time Frame: baseline, 12 weeks
baseline, 12 weeks
Change in GA/HbA1c ratio from baseline
Time Frame: baseline, 12 weeks
baseline, 12 weeks
Change in fasting blood sugar from baseline
Time Frame: baseline, 12 weeks
baseline, 12 weeks
Change in total cholesterol from baseline
Time Frame: baseline, 12 weeks
baseline, 12 weeks
Change in triglycerides from baseline
Time Frame: baseline, 12 weeks
baseline, 12 weeks
Change in LDL-cholesterol from baseline
Time Frame: baseline, 12 weeks
baseline, 12 weeks
Change in HDL-cholesterol from baseline
Time Frame: baseline, 12 weeks
baseline, 12 weeks
Change in Homeostasis Model Assessment-Insulin resistance(HOMA-IR) from baseline
Time Frame: baseline, 24 weeks
a marker of insulin resistance
baseline, 24 weeks
Change in Homeostasis Model Assessment - beta cell (HOMA-beta) from baseline
Time Frame: baseline, 24 weeks
a marker of beta cell function
baseline, 24 weeks
Change in highly sensitive C reactive protein(hs-CRP) from baseline
Time Frame: baseline, 24 weeks
a marker of inflammation
baseline, 24 weeks
Change in Plasmonogen activator inhibitor-1(PAI-1) from baseline
Time Frame: baseline, 24 weeks
baseline, 24 weeks
Change in B-type natriuretic pepetide(BNP) from baseline
Time Frame: baseline, 24 weeks
baseline, 24 weeks
event rate of hypoglycemia
Time Frame: upto 24 weeks
A number of total event of hypoglycemia defined as blood glucose <70mg/dL or subjective symptom of typical hypoglycemia
upto 24 weeks
No of subject with adverse event of special interest
Time Frame: upto 24 weeks

The event of special interest include

  • heart failure
  • cardiovascular effect other than heart failure
  • edema
  • weight gain
  • urinary bladder tumor
  • macular edema
  • fracture of bone
  • pancreatitis
upto 24 weeks
The number of serious adverse events
Time Frame: upto 24 weeks
upto 24 weeks
The number of subject with hypersensitivity to study drugs
Time Frame: upto 24 weeks
upto 24 weeks
The number of subject with any abnormality of laboratory evaluation
Time Frame: 12 week
  • Complete Blood count
  • BUN, Creatinine, AST, ALT, Calcium, Phosphorous, Sodium, Potassium, Total Protein, Albumin, Total Bilirubin, Gamma-glutamyl transferase, Alkaline phosphatase, Creatinine Kinase, amylase, lipase
  • Urine analysis including microscopic examination
12 week
The number of subject with any abnormality of laboratory evaluation
Time Frame: 24 week
  • Complete Blood count
  • Blood urea nigrogen, Creatinine, Aspartate aminotransferase, Alanine Aminotransferase, Calcium, Phosphorous, Sodium, Potassium, Total Protein, Albumin, Total Bilirubin, Gamma-glutamyl transferase, Alkaline phosphatase, Creatinine Kinase, amylase, lipase
  • Urine analysis including microscopic examination
24 week
The number of subject with any change of findings in Chest X-ray from baseline
Time Frame: 24 week
24 week
The number of subject with any change of findings in electrocardiogram from baseline
Time Frame: 24 week
24 week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kun-Ho Yoon

Collaborators

Takeda

Investigators

  • Principal Investigator: Kun-Ho Yoon, MD, PhD, Seoul St Mary's Hospital, The Catholic Univerisity of Korea

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 1, 2014

Primary Completion (ACTUAL)

October 22, 2018

Study Completion (ACTUAL)

January 28, 2019

Study Registration Dates

First Submitted

August 29, 2014

First Submitted That Met QC Criteria

August 29, 2014

First Posted (ESTIMATE)

September 3, 2014

Study Record Updates

Last Update Posted (ACTUAL)

February 8, 2019

Last Update Submitted That Met QC Criteria

February 7, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALO-IIT-012

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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