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Completed

NCT Number: NCT02231021

The Practical Evidence of Antidiabetic Combination Therapy 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.

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Key information

Conditions

Type 2 Diabetes Mellitus Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

19 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

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

Seoul, 137-701, South Korea

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Alogliptin

Drug

alogliptin 25 mg add-on background medication metformin

Other names: Nesina

pioglitazone

Drug

pioglitazone 30 mg add-on background medication metformin

Other names: actos

alogliptin + pioglitazone

Drug

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

Other names: Nesina, Actos

Primary outcomes

  1. Change in glycohemoglobin(HbA1c) from baseline

    Time frame: baseline, 24 weeks

Secondary outcomes

  1. Proportion of subjects achieving HbA1c < 7.0%

    Time frame: 24 week

  2. Proportion of subjects achieving HbA1c <6.5%

    Time frame: 24 week

  3. Changes in glycated albumin(GA) from baseline

    Time frame: baseline, 24 weeks

  4. Change in GA/HbA1c ratio from baseline

    Time frame: baseline, 24 weeks

  5. Change in fasting blood sugar from baseline

    Time frame: baseline, 24 weeks

  6. Incidence of hyperglycemic rescue

    Time frame: 12 week

    at Week 12, HbA1c >9.0%

  7. Change in HbA1c from baseline

    Time frame: 12 week

  8. Change in total cholesterol from baseline

    Time frame: baseline, 24 weeks

  9. Change in triglycerides from baseline

    Time frame: baseline, 24 weeks

  10. Change in LDL-cholesterol from baseline

    Time frame: baseline, 24 weeks

  11. Change in HDL-cholesterol from baseline

    Time frame: baseline, 24 weeks

  12. Changes in glycated albumin(GA) from baseline

    Time frame: baseline, 12 weeks

  13. Change in GA/HbA1c ratio from baseline

    Time frame: baseline, 12 weeks

  14. Change in fasting blood sugar from baseline

    Time frame: baseline, 12 weeks

  15. Change in total cholesterol from baseline

    Time frame: baseline, 12 weeks

  16. Change in triglycerides from baseline

    Time frame: baseline, 12 weeks

  17. Change in LDL-cholesterol from baseline

    Time frame: baseline, 12 weeks

  18. Change in HDL-cholesterol from baseline

    Time frame: baseline, 12 weeks

  19. Change in Homeostasis Model Assessment-Insulin resistance(HOMA-IR) from baseline

    Time frame: baseline, 24 weeks

    a marker of insulin resistance

  20. Change in Homeostasis Model Assessment - beta cell (HOMA-beta) from baseline

    Time frame: baseline, 24 weeks

    a marker of beta cell function

  21. Change in highly sensitive C reactive protein(hs-CRP) from baseline

    Time frame: baseline, 24 weeks

    a marker of inflammation

  22. Change in Plasmonogen activator inhibitor-1(PAI-1) from baseline

    Time frame: baseline, 24 weeks

  23. Change in B-type natriuretic pepetide(BNP) from baseline

    Time frame: baseline, 24 weeks

  24. 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

  25. 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

  26. The number of serious adverse events

    Time frame: upto 24 weeks

  27. The number of subject with hypersensitivity to study drugs

    Time frame: upto 24 weeks

  28. 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

  29. 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

  30. The number of subject with any change of findings in Chest X-ray from baseline

    Time frame: 24 week

  31. The number of subject with any change of findings in electrocardiogram from baseline

    Time frame: 24 week

Sponsors and collaborators

Lead sponsor

Kun-Ho Yoon

Other

Collaborators

  • Takeda

Registry information

Official study 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

Acronym: PEAK

Important dates

Study start
2014
Primary completion
2018
Study completion
2019
First posted
Sep 3, 2014
Registry last updated
Feb 8, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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