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Trial record 63 of 668 for:    diabetes AND Hypoglycemic | Recruiting, Not yet recruiting, Available Studies

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

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ClinicalTrials.gov Identifier: NCT02231021
Recruitment Status : Recruiting
First Posted : September 3, 2014
Last Update Posted : July 14, 2017
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
Kun-Ho Yoon, The Catholic University of Korea

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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: alogliptin Drug: Pioglitazone Drug: alogliptin + pioglitazone Phase 4

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  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : September 2014
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : November 2018

Resource links provided by the National Library of Medicine


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:
  • Nesina
  • Actos

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 Name: 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 Name: actos




Primary Outcome Measures :
  1. Change in glycohemoglobin(HbA1c) from baseline [ Time Frame: baseline, 24 weeks ]

Secondary Outcome Measures :
  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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02231021


Contacts
Contact: Kun-Ho Yoon, MD, PhD. 82-2-2258-1252 yoonk@catholic.ac.kr
Contact: Yoon-Hee Choi, MD, PhD 82-2-2258-1252 choiyh@catholic.ac.kr

Locations
Korea, Republic of
Seoul St Mary's Hospital, The Catholic University of Korea Recruiting
Seoul, Korea, Republic of, 137-701
Principal Investigator: Kun-Ho Yoon, MD, PhD         
Sub-Investigator: Yoon-Hee Choi, MD, PhD         
Sub-Investigator: Hye-Kyung Yang, MD         
Sponsors and Collaborators
Kun-Ho Yoon
Takeda
Investigators
Principal Investigator: Kun-Ho Yoon, MD, PhD Seoul St Mary's Hospital, The Catholic Univerisity of Korea

Responsible Party: Kun-Ho Yoon, Professor, The Catholic University of Korea
ClinicalTrials.gov Identifier: NCT02231021     History of Changes
Other Study ID Numbers: ALO-IIT-012
First Posted: September 3, 2014    Key Record Dates
Last Update Posted: July 14, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Kun-Ho Yoon, The Catholic University of Korea:
Diabetes Mellitus, Type 2
alogliptin
pioglitazone
DPP4 inhibitor
thiazolidinedione

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypoglycemic Agents
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pioglitazone
Alogliptin
Metformin
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action