Efficacy of Pioglitazone in Patients With Inadequately Controlled Type 2 Diabetes Mellitus Treated With Stable Triple Oral Therapy

Overview[ - collapse ][ - ]

Purpose The purpose of this study is to evaluate the efficacy of pioglitazone 30 mg as compared with pioglitazone 15 mg on glycemic control as when used in patients with inadequately controlled type 2 diabetes mellitus treated with fixed combinations of metformin and sulfonylurea.
ConditionType II Diabetes Mellitus
InterventionDrug: Pioglitazone
Drug: Metformin
Drug: Sulfonylurea
PhasePhase 4
SponsorTakeda
Responsible PartyTakeda
ClinicalTrials.gov IdentifierNCT01972724
First ReceivedOctober 24, 2013
Last UpdatedOctober 24, 2013
Last verifiedOctober 2013

Tracking Information[ + expand ][ + ]

First Received DateOctober 24, 2013
Last Updated DateOctober 24, 2013
Start DateNovember 2013
Estimated Primary Completion DateNovember 2014
Current Primary Outcome MeasuresChange From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 [Time Frame: Baseline and Week 24] [Designated as safety issue: No]The change from Baseline in glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at Week 24.
Current Secondary Outcome MeasuresChange From Baseline in Fasting Plasma Glucose at Week 24 [Time Frame: Baseline and Week 24] [Designated as safety issue: No]The change between the value of fasting serum glucose collected at Week 24 and fasting serum glucose collected at Baseline.

Descriptive Information[ + expand ][ + ]

Brief TitleEfficacy of Pioglitazone in Patients With Inadequately Controlled Type 2 Diabetes Mellitus Treated With Stable Triple Oral Therapy
Official TitleA 24-Week, Randomized, Double-Blind, Phase IV Trial to Evaluate the Efficacy of Pioglitazone 30 mg in Patients With Inadequately Controlled Type 2 Diabetes Mellitus Treated With Stable Triple Oral Therapy of Metformin, Sulfonylurea, and Pioglitazone 15 Mg (ADD Trial)
Brief Summary
The purpose of this study is to evaluate the efficacy of pioglitazone 30 mg as compared with
pioglitazone 15 mg on glycemic control as when used in patients with inadequately controlled
type 2 diabetes mellitus treated with fixed combinations of metformin and sulfonylurea.
Detailed Description
The drug being tested in this study is called pioglitazone. Pioglitazone is being tested to
treat glycemic control in adults with inadequately controlled type 2 diabetes mellitus. This
study will look at glycemic control in people who take triple oral therapy of metformin,
sulfonylurea, and pioglitazone 15 mg.

The study will enroll approximately 310 patients. Participants will be randomly assigned (by
chance, like flipping a coin) to one of the two treatment groups—which will remain
undisclosed to the patient and study doctor during the study (unless there is an urgent
medical need):

- Pioglitazone 15 mg + Metformin and sulfonylurea

- Pioglitazone 30 mg + Metformin and sulfonylurea

All participants will be asked to take one pioglitazone tablet at the same time each day
throughout the study as well as continuing their previous dose of metformin and
sulfonylurea..

This multi-centre trial will be conducted in Korea. The overall time to participate in this
study is up to 25 weeks. Participants will make 4 visits to the hospital or
endocrinologist's office, and will be contacted by telephone 7 days after last dose of study
drug for a follow-up assessment.
Study TypeInterventional
Study PhasePhase 4
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
ConditionType II Diabetes Mellitus
InterventionDrug: Pioglitazone
Pioglitazone tablets
Other Names:
ACTOSDrug: Metformin
Metformin tablets
Drug: Sulfonylurea
Sulfonylurea tablets
Study Arm (s)
  • Experimental: Pioglitazone 15 mg
    Pioglitazone 15 mg tablets, orally, once daily, and metformin and sulfonylurea will be administered according to the prescribing information of the approved Korean label, for up to 24 weeks.
  • Experimental: Pioglitazone 30 mg
    Pioglitazone 30 mg tablets, orally, once daily, and metformin and sulfonylurea will be administered according to the prescribing information of the approved Korean label, for up to 24 weeks.

Recruitment Information[ + expand ][ + ]

Recruitment StatusNot yet recruiting
Estimated Enrollment310
Estimated Completion DateNovember 2014
Estimated Primary Completion DateNovember 2014
Eligibility Criteria
Inclusion Criteria:

1. Institutional Review Board (IRB)-approved written informed consent form (ICF) must be
obtained from the patient or legally authorized representative prior to any trial
related procedure (including withdrawal of prohibited medication, if applicable)

2. Patients with a history of clinical diagnosis of established type 2 diabetes mellitus
defined by the ADA criteria 2012

3. Male or female between 18 and 80 years of age

4. Patients with stable triple oral therapy of metformin + sulfonylurea + pioglitazone
(ACTOS) 15 mg or ACTOSMET(Pioglitazone 15mg/Metformin 850mg) and sulfonylurea for at
least 12 weeks at the screening visit

5. Patients with HbA1c ≥7.0% at the screening visit

6. Patients with C-peptide ≥1.0 ng/mL at the screening visit

7. Females of childbearing potential who are sexually active must agree to use adequate
contraception, and can neither be pregnant nor lactating from screening throughout
the duration of the study, up to 60 days after the last dose of the study medication

Exclusion Criteria:

1. Patients with type 1 diabetes mellitus or secondary forms of diabetes

2. Patients who have been treated with insulin for ≥7 days within 3 months prior to the
screening visit

3. Patients with a history of bladder cancer or patients with active bladder cancer

4. Patients with a history of acute diabetic complications such as diabetic ketoacidosis

5. Patients with a history of acute or chronic metabolic acidosis, including diabetic
ketoacidosis

6. Patients with unstable or rapidly progressive diabetic retinopathy, nephropathy
(estimated glomerular filtration rate [eGFR] <60mL/min/1.73m2)

7. Patients with cardiac insufficiency (e.g., a myocardial infarction, a coronary
angioplasty or bypass graft, unstable angina, transient ischemic attacks, or a
documented cerebrovascular accident within 6 months prior to the screening visit)

8. Patients with cardiac failure or history of cardiac failure (New York Heart
Association [NYHA] Stages 3 to 4)

9. Patients with a serum alanine transaminase (ALT) level ≥2.5 times the upper limit of
normal (ULN), active liver disease, or jaundice

10. Patients taking concomitant gemfibrozil or other strong cytochrome P450 (CYP)2C8
inhibitors

11. Patients with a history of recurrent or severe hypoglycemia

12. Patients with a history of any hemoglobinopathy (such as hemolytic anemias or sickle
cell disease) that may affect determination of HbA1c

13. Patients with uninvestigated microscopic hematuria

14. Patients with genetic problems such as galactose intolerance, Lapp lactase
deficiency, or glucose-galactose malabsorption, since the study drug contains lactose

15. Patients with any other condition judged by the Investigator as unsuitable for the
study

16. Patients who have used any investigational or experimental drugs or devices within 60
days of the screening visit

17. Lactating or pregnant female. A positive pregnancy test before the first
administration of investigational medicinal product or breastfeeding

18. Male patients planning to father during clinical trial conduct or within 3 months
after the last planned dose of the IMP

19. Patients were previously enrolled into the current clinical trial

20. Prior to the start of the clinical trial the patient participated in the active
treatment phase of another clinical trial where a persisting pharmacodynamic effect
of the IMP of that clinical trial cannot be excluded (e.g., patient is well into a
treatment-free follow-up phase)

21. Patients are considered unable or unwilling to co-operate adequately, i.e., to follow
clinical trial procedures and Investigator instructions adequately (e.g., language
difficulties, etc.) or patients are anticipated not to be available for scheduled
clinical trial visits/procedures.
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Takeda Study Registration Call Center
800-778-2860
medicalinformation@tpna.com
Location CountriesKorea, Republic of

Administrative Information[ + expand ][ + ]

NCT Number NCT01972724
Other Study ID NumbersPG-9999-301-KR
Has Data Monitoring CommitteeNo
Information Provided ByTakeda
Study SponsorTakeda
CollaboratorsNot Provided
Investigators Study Director: Medical Director Takeda
Verification DateOctober 2013

Locations[ + expand ][ + ]

Korea, Republic of
Chagwon, Korea, Republic of
Not yet recruiting
Korea, Republic of
Daegu, Korea, Republic of
Not yet recruiting
Korea, Republic of
Daejeon, Korea, Republic of
Not yet recruiting
Korea, Republic of
Gwangju, Korea, Republic of
Not yet recruiting
Korea, Republic of
Jeonju, Korea, Republic of
Not yet recruiting
Korea, Republic of
Seoul, Korea, Republic of
Not yet recruiting
Korea, Republic of
Seoungnam, Korea, Republic of
Not yet recruiting
Korea, Republic of
Ulsan, Korea, Republic of
Not yet recruiting
Korea, Republic of
Wonju, Korea, Republic of
Not yet recruiting