Efficacy, Safety and Tolerability of AD-4833-536 in Subjects With Type 2 Diabetes Mellitus - Full Text View

Sponsor:	Takeda Global Research & Development Center, Inc.
Information provided by:	Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:	NCT00376181

Purpose

The purpose of this study is to evaluate the efficacy and safety of pioglitazone and TAK-536 in subjects with type 2 diabetes mellitus with poor glycemic control.

Condition	Intervention	Phase
Type 2 Diabetes	Drug: Pioglitazone and TAK-536 Drug: Pioglitazone	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Dose Comparison, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Phase 3 Double-Blind, Randomized, Placebo-Controlled Study to Determine the Efficacy, Safety, and Tolerability of AD-4833-536 in the Treatment of Subjects With Type 2 Diabetes

Resource links provided by NLM:

MedlinePlus related topics: Diabetes

Drug Information available for: Pioglitazone Pioglitazone hydrochloride

U.S. FDA Resources

Further study details as provided by Takeda Global Research & Development Center, Inc.:

Primary Outcome Measures:

Change from Baseline in Glycosylated Hemoglobin. [ Time Frame: Week 24 or Final Visit ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change from Baseline in Glycosylated Hemoglobin. [ Time Frame: Weeks 4, 8, 12, 16, 20, and 24 or Final Visit ] [ Designated as safety issue: No ]
Change from Baseline in Diastolic Blood Pressure [ Time Frame: Weeks 4, 8, 12, 16, 20, and 24 or Final Visit ] [ Designated as safety issue: No ]
Change from Baseline in Systolic Blood Pressure [ Time Frame: Weeks 4, 8, 12, 16, 20, and 24 or Final Visit ] [ Designated as safety issue: No ]

Enrollment:	96
Study Start Date:	June 2006
Study Completion Date:	May 2007
Primary Completion Date:	May 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: Pioglitazone and TAK-536 Pioglitazone 45 mg and TAK-536 20 mg combination tablets, orally, once daily for up to 24 weeks.
2: Experimental	Drug: Pioglitazone and TAK-536 Pioglitazone 45 mg and TAK-536 40 mg combination tablets, orally, once daily for up to 24 weeks.
3: Active Comparator	Drug: Pioglitazone Pioglitazone 45 mg, tablets, orally, once daily for up to 24 weeks.

Detailed Description:

Type 2 diabetes is a chronic disease. In the United States, an estimated 21 million people have diabetes, with type 2 diabetes occurring in 90% to 95% of cases. Hypertension (high blood pressure) affects approximately 50 million individuals in the United States. The association of diabetes and hypertension is increased in this population; hypertension is more common in persons with diabetes while individuals with hypertension are 2.5 times more likely to develop diabetes than those who have normal blood pressure. As a result, more than 70% of adults with diabetes have hypertension (defined as having blood pressure greater than or equal to 130/80 mm Hg or using prescription medication for hypertension).

Patients with type 2 diabetes and hypertension are at high risk of other illnesses and death. Diabetes and hypertension are associated with insulin resistance (normal amounts of insulin are no adequate to produce a normal insulin response from fat, muscle and liver cells). and hyperinsulinemia (excess levels of insulin in the blood), which are independent risk factors for cardiovascular (heart vessel) disease. Individuals with type 2 diabetes carry a 2 to 4- time greater risk of cardiovascular disease and stroke compared with the general population. Uncontrolled hypertension also is associated with an increased risk of cardiovascular disease and stroke.

Takeda Global Research and Development Center, Inc. is developing a fixed-dose combination product that combines a commercially available, anti-diabetes agent (pioglitazone) with an antihypertensive agent (TAK-536) that increases the glucose lowering effects of pioglitazone.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

Type 2 diabetes with glycosylated hemoglobin of greater than or equal to 9.0 to less than or equal to 11.0% at Screening.
Documented hypertension.
On a stable diet and exercise program in addition to metformin alone or combination of metformin and a sulfonylurea for a minimum of 8 weeks prior to screening.
If receiving antihypertensive therapy, must be on no more than 3 agents and be on a stable regimen.
Clinical laboratory evaluations (including clinical chemistry, hematology, and urinalysis) within the reference range unless the results are deemed not clinically significant for inclusion into this study by the investigator.
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.

Exclusion Criteria

Type 1 diabetes mellitus.
Diastolic blood pressure greater than 104 mm Hg at randomization visit.
Currently taking an angiotensin II-receptor blocker.
Unstable angina or heart failure of any etiology with New York Heart Association functional class III or IV.
History of myocardial infarction, cerebrovascular accident (stroke), percutaneous coronary intervention, coronary artery bypass graft or transient ischemic attack within the previous six months.
Clinically significant cardiac conduction defects.
Secondary hypertension of any etiology.
Body mass index greater than 45 kg/m2
Has significant renal dysfunction.
History of drug abuse or a history of alcohol abuse within the past 2 years.
Previous history of cancer, other than basal cell carcinoma or stage 1 squamous cell carcinoma of the skin that has not been in remission for at least 5 years prior to the first dose of study drug.
Alanine transaminase or aspartate transaminase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.
Serum potassium greater than the upper limit of normal.
Currently participating in another investigational study or has participated in an investigational study within 30 days prior to Randomization.
Any other serious disease or condition that would compromise subject safety, might affect life expectancy, or make it difficult to successfully manage and follow the subject according to the protocol.
Is hypersensitive to angiotensin II receptor blockers.
Is hypersensitive to thiazolidinediones.
Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:
- any anti-diabetic agent (including thiazolidinediones and/or insulin) except for metformin or a combination of metformin and a sulfonylurea
- niacin more than 200mg per day
- tricyclic antidepressants or phenothiazines
- Angiotensin II receptor blockers
- Thiazolidinediones
- Insulin

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00376181

Show 73 Study Locations

Sponsors and Collaborators

Takeda Global Research & Development Center, Inc.

Investigators

Study Director:

VP Clinical Science Strategy

Takeda Global Research & Development Center, Inc.

More Information

Additional Information:

ACTOS® Package Insert This link exits the ClinicalTrials.gov site

FDA Safety Alerts and Recalls This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Takeda Global Research & Development Center, Inc. ( Sr. VP, Clinical Science )
Study ID Numbers:	01-06-TL-OPI536-003
Study First Received:	September 12, 2006
Last Updated:	January 24, 2009
ClinicalTrials.gov Identifier:	NCT00376181 History of Changes
Health Authority:	United States: Food and Drug Administration; Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica; Peru: General Directorate of Pharmaceuticals, Devices, and Drugs; Chile: Instituto de Salud Publica de Chile; Mexico: Ministry of Health

Keywords provided by Takeda Global Research & Development Center, Inc.:

type 2 diabetes
hypertension
blood pressure
diastolic blood pressure

Additional relevant MeSH terms:

Hypoglycemic Agents
Metabolic Diseases
Pioglitazone
Physiological Effects of Drugs
Diabetes Mellitus, Type 2

Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 08, 2010