An Extension Study of PEAK Trial (PEAK-E)

An Extension Study of Protocol ALO-IIT(PEAK Study) to Examine the Long-term Efficacy and Safety of Metformin + Alogliptin + Pioglitazone Triple Combination Therapy in the Korean Type 2 Diabetes Patients

Double blind, three arm, comparative intervention trial for 24 weeks(PEAK study) with open label extension trial for 28 weeks followed by 2 year observational study.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: alogliptin+pioglitazone; Drug: alogliptin; Drug: pioglitazone

Detailed Description

PEAK trial is now undergoing (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, Takeda No. ALO-IIT-012).

Duration of combination treatment is 24 week in the PEAK trial. Long-term efficacy and safety of alogliptin + pioglitazone + metformin combination therapy is not defined in Korea yet.

Thus, extension of the PEAK trial for the longer treatment upto 1 year has been planned.

PEAK trial will be followed by another 28 week open-label treatment of the same drug as initial randomization (total duration of treatment as randomized 52 week), and followed by 2 year of observation.

During observation period, any antidiabetic medication can be added/changed when HbA1c of the subject is off target 7% with clinician's clinical decision.

After 3 years of initial randomization, durability of glucose control will be assessed between 3 treatment group.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

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:

• Completed "ALO-IIT-012(PEAK study)", without major protocol deviations.
• Male, or female, 19 years to 75 years.
• Female with childbearing potential who has a negative urine pregnancy test result at study start and willing to continue practice appropriate birth control during the entire duration of study
• Subjects completed PEAK can be included within 30 days after End Of the Study
• Subjects completed PEAK can be included if their treatment is the same as randomized even after 30 days of End Of the Study.

Exclusion Criteria:

• eGFR(Epidermal growth factor receptor) < 50mL/min
• AST(aspartate aminotransferase)/ALT(alanine aminotransaminase) >2.5 upper limit of normal
• Pregnant or lactating women
• Subject who the investigator deems inappropriate to participate in this study
• Patients with a history of bladder cancer or patients with active bladder cancer
• Patients with uninvestigated macroscopic hematuria
• Patients with cardiac failure or a history of cardiac failure (New York Heart Association [NYHA] Stages 3 to 4)
• Patients with genetic problems such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption, since this study drug contains lactose

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: alogliptin+pioglitazone; A group who treat with alogliptin+pioglitazone: The Combination of Alogliptin 25 mg and pioglitazone 30 mg daily add on metformin for 28 week as extension and followed by 2 years of observation	Drug: alogliptin+pioglitazone; alogliptin and pioglitazone add on metformin; Other Names: nesina, actos
Active Comparator: alogliptin; A group who treat with alogliptin: Alogliptin 25 mg daily add on metformin for for 28 week as extension and followed by 2 years of observation	Drug: alogliptin; nesina add on metformin; Other Names: nesina
Active Comparator: pioglitazone; A group who treat with pioglitazone: Pioglitazone 30 mg daily add on metformin for for 28 week as extension and followed by 2 years of observation	Drug: pioglitazone; actos add on metformin; Other Names: actos

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects achieving HbA1c <7% after 36 month treatment	The proportion of subjects achieving HbA1c on target < 7.0% after 36 month.	36 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects achieving HbA1c <6.5% after 36 month treatment	The proportion of subjects achieving HbA1c on target < 6.5% after 36 month.	36 Months after randomization
Proportion of subjects achieving HbA1c <7% after 12 month treatment	The proportion of subjects achieving HbA1c on target < 7.0% after 12 month.	12 Months after randomization
Change in glycated hemoglobin(HbA1c) from baseline to 12 month	Change from baseline in HbA1c after 6 month of double blinded treatment followed by 6 month open treatment	baseline, 12 months
Change in HOMA-IR(homeostasis model assessment of insulin resistance) from baseline to 36 month	Change from baseline in HOMA-IR(homeostasis model assessment of insulin resistance) after 12 month of randomized treatment followed by 24 month observation.	baseline, 36 months
change of HOMA-beta(homeostasis model assessment of beta cell) from baseline to 36 month	Change from baseline in HOMA-beta(homeostasis model assessment of beta cell) after 12 month of randomized treatment followed by 24 month observation.	baseline, 36 months

Collaborators and Investigators

• Sponsor: Kun-Ho Yoon
• Collaborators: Takeda
• Investigators: Principal Investigator: Kun-Ho Yoon, MD, PhD, Seoul St Mary's Hospital, The Catholic University of Korea

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2016
• Primary Completion (Actual): December 19, 2018
• Study Completion (Actual): February 28, 2019

Study Registration Dates

• First Submitted: April 29, 2016
• First Submitted That Met QC Criteria: May 3, 2016
• First Posted (Estimate): May 5, 2016

Study Record Updates

• Last Update Posted (Actual): June 5, 2019
• Last Update Submitted That Met QC Criteria: June 3, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Pioglitazone; Alogliptin
• Other Study ID Numbers: PEAK-E

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO