Safety Study of Pioglitazone Compared To Glyburide on Liver Function

NCT00494312 | Completed Phase 4 DMC

• 2 other identifiers: 01-00-TL-OPI-506U1111-1114-1564
• Study Type: interventional
• Target: 2,120
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to determine the liver safety of pioglitazone, once daily (QD), versus glyburide taken with metformin and insulin.

Conditions

Diabetes Mellitus; Liver

Keywords

Glucose Metabolism Disorder; Dysmetabolic Syndrome; Type II Diabetes; Diabetes Mellitus; Lipoatrophic; Dyslipidemia; Liver; Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Incidence of liver inflammation or injury greater than 3 times the upper limit of normal, as monitored by serum alanine aminotransaminase elevation.

  At All Visits

Secondary Outcomes (4)

• Incidence of alanine aminotransferase greater than 8 times the upper limit of normal.

  At All Visits

• Incidence of alanine aminotransferase greater than 3 times the upper limit of normal but less than or equal to 8 times the upper limit of normal on 4 consecutive measurements within a 3-month period.

  At All Visits

• Incidence of alanine aminotransferase greater than 3 times the upper limit of normal and total bilirubin greater than 2 times the upper limit of normal.

  At All Visits

• Change from Baseline or greater than 1.5 times the upper limit of normal (whichever is greater) in the level of alanine aminotransferase, aspartate aminotransferase, total or direct bilirubin, alkaline phosphatase or gamma-glutamyl transpeptidase.

  At All Visits

Study Arms (2)

Pioglitazone QD

EXPERIMENTAL

Drug: Pioglitazone

Glyburide QD

ACTIVE COMPARATOR

Drug: Glyburide

Interventions

Pioglitazone DRUG

Pioglitazone 15 mg or 30 mg titrated to 45 mg, tablets, orally, once daily and glyburide placebo-matching capsules, orally, once daily for up to 156 weeks.

Also known as: Actos, AD-4833

Pioglitazone QD

Glyburide DRUG

Pioglitazone placebo-matching tablets, orally, once daily and glyburide 5 mg or 10 mg titrated to 15 mg, capsules, orally, once daily for up to 156 weeks.

Glyburide QD

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Diagnosis of type 2 (non-insulin dependent) diabetes mellitus as defined by the diagnostic criteria of the American Diabetes Association and currently taking glyburide, glipizide, glimepiride, or metformin alone, or glyburide, glipizide, or glimepiride in combination with metformin
• Glycosylated hemoglobin level greater than or equal to 7.0%
• Fasting C-peptide level greater than or equal to 0.7 ng/mL.

You may not qualify if:

• Type 1 (insulin-dependent) diabetes mellitus.
• Prior exposure to a thiazolidinedione, except subjects who discontinued use of troglitazone in March or April of 2000, provided they were not experiencing adverse effects and were not then taking thiazolidinediones.
• Participating in another investigational study or had participated in an investigational trial within the preceding 2 months.
• History of ketoacidosis.
• The subject had significant diabetic nephropathy, defined as a serum creatinine level greater than or equal to 1.5 mg/dL for men and greater than or equal to 1.4 mg/dL for women, or urinary protein excretion greater than or equal to 2 plus as measured by the Combistix (or equivalent) method, except subjects with proteinuria are eligible if repeat testing within 2 weeks indicates the proteinuria had resolved.
• Anemia with a hemoglobin level less than12 g/dL for men and less than10 g/dL for women.
• The subject had a history of drug or alcohol abuse within the preceding 2 years.
• The subject had a diastolic blood pressure greater than100 mm Hg or a systolic blood pressure greater than180 mm Hg.
• The subject had evidence of ongoing cardiac rhythm disturbance, delayed QT waves, or second-degree atrioventricular heart block. Uncomplicated first-degree atrioventricular block was allowed.
• Significant cardiovascular disease including, but not limited to, New York Heart Association Functional (Cardiac) Classification III or IV.
• History of myocardial infarction, acute cardiovascular event, or cerebrovascular accident within the preceding 6 months.
• Previous history of cancer that was not in remission for at least 5 years before administration of the first dose of study drug. Except, basal cell or Stage I squamous cell carcinoma.
• The subject had a BMI less than 20 or greater than 48 (calculated as weight \[kg\]/height \[m2\]).
• Alanine aminotransferase level greater than or equal 2.5time the upper limit of normal or a history of liver disease, jaundice, hepatitis, or biliary tract disease (except for uncomplicated and treated gall stones by either lithotomy or cholecystectomy).
• Unwilling or unable to comply with the protocol or attend scheduled appointments.

Sponsors & Collaborators

• Takeda: lead

Related Publications (2)

• Tolman KG, Fonseca V, Tan MH, Dalpiaz A. Narrative review: hepatobiliary disease in type 2 diabetes mellitus. Ann Intern Med. 2004 Dec 21;141(12):946-56. doi: 10.7326/0003-4819-141-12-200412210-00011.

  PMID: 15611492 RESULT

• Tolman KG, Freston JW, Kupfer S, Perez A. Liver safety in patients with type 2 diabetes treated with pioglitazone: results from a 3-year, randomized, comparator-controlled study in the US. Drug Saf. 2009;32(9):787-800. doi: 10.2165/11316510-000000000-00000.

  PMID: 19670918 DERIVED

Related Links

• ACTOS® Package Insert

MeSH Terms

Conditions

Diabetes Mellitus; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Dyslipidemias

Interventions

Pioglitazone; Glyburide

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfonylurea Compounds; Urea; Amides; Sulfones

Study Officials

• VP Clinical Science Strategy

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2007
• First Posted: June 29, 2007
• Study Start: October 1, 2000
• Primary Completion: June 1, 2005
• Study Completion: June 1, 2005
• Last Updated: February 28, 2012

Record last verified: 2012-02