Official Title: “A Phase 4, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of Pioglitazone Compared to Placebo on Bone Metabolism in Impaired Fasting Glucose, Postmenopausal Women for One Year of Treatment”

This is a 1 year study to evaluate the effect of pioglitazone HCL on bone metabolism in postmenopausal women with impaired fasting glucose.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2010

Subjects participating in this study will be randomized to receive an initial starting dose of 30 mg pioglitazone or matching pioglitazone placebo, and then after one month the dose will be titrated to either 45 mg pioglitazone or matching pioglitazone placebo, where treatment will continue for one year. After one year, subjects will continue with a 6 month wash-out period to assess the potential persistence of pioglitazone's effects on bone metabolism.

Intervention(s) in this Clinical Trial

• Drug: Pioglitazone HCl
  • Pioglitazone HCl 30 mg tablet, orally, once daily for 4 weeks, then increased to Pioglitazone HCl 45 mg tablet, orally, once daily for 48 weeks.
• Drug: Pioglitazone HCl
  • Pioglitazone HCl placeobo-matching tablet, orally, once daily for 52 weeks.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Placebo Comparator: 2

Primary Measures

• Percent change from baseline to 12 months in bone mineral density in the total proximal femur by dual-energy x-ray absorptiometry (DXA).
  • Time Frame: 12 Months
    Safety Issue?: No

Secondary Measures

• Percent change from 12 months to 18 months in bone mineral density in the total proximal femur by dual-energy x-ray absorptiometry (DXA).
  • Time Frame: 18 Months
    Safety Issue?: No

Inclusion Criteria:

• The subject is female and has not experienced menses for at least 5 years.
• The subject has a FPG ≥100 and <126 mg/dL at Screening, or a 2-hour post-oral glucose tolerance test ≥ 140 and ≤199 mg/dL at Screening.
• The subject has a BMI ≥16 and ≤35 kg/m2 and weighs <300 pounds (approximately 136 kilograms).
• The subject must agree to take a daily supplement of Vitamin D (a minimum of 800 IU daily) and calcium (a minimum of 1100 mg daily) during the treatment and wash-out periods.
• The subject has clinical laboratory evaluations (including clinical chemistry [except
• FPG], hematology, and complete urinalysis [fasted for at least 8 hours]) within the reference range for the testing laboratory unless the results are deemed not clinically significant by the investigator or sponsor.
• The subject is in good health as determined by the physician (ie, via medical history and physical examination) at Screening.

Exclusion Criteria:

• The subject has a fasting triglyceride level >500 mg/dL.
• The subject has a hemoglobinopathy causing anemia or interfering with glycosylated hemoglobin (A1c) assays.
• The subject has an alanine transaminase (ALT) level ≥2.5 times the upper limit of normal (ULN), active liver disease, or jaundice.
• The subject has vitamin D (25-OH-D) <20 ng/mL.
• The subject has Baseline Bone Mineral Density (BMD) defined as a T-score <-2.0 at the total hip, spine, or femoral neck based on Caucasian reference values.
• The subject has unexplained microscopic or macroscopic hematuria confirmed by repeat testing.
• The subject has any of the following disorders:
• Rheumatoid arthritis.
• Thyroid, parathyroid, pituitary, nutritional, inflammatory, gastrointestinal, autoimmune, or renal or other disease known to affect bone metabolism.
• A personal history of kidney stones.
• The subject has a clinical history after age 45 of wrist, hip or leg fractures.
• The subject has more than 1 mild asymptomatic vertebral deformity or any vertebral deformity attributed to osteoporosis.
• The subject has a known history of drug abuse (defined as illicit drug use) or a known history of alcohol abuse.
• The subject has signs and/or symptoms of heart failure.
• The subject is taking any of the excluded medications as listed in the Excluded
• Medications Section.
• The subject is not capable of understanding and complying with protocol requirements.
• The subject or the subject's legally acceptable representative is unable to understand verbal or written English or any other language for which a certified translation of the approved informed consent is available.
• The subject currently is participating in another investigational study or has participated in an investigational study within the past 30 days or 5 half lives of the investigational product, whichever is longer.
• The subject has any other serious disease or condition at screening or at randomization that might make it difficult to successfully manage and follow up with the subject according to the protocol.
• The subject has a 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.
• Subjects who are taking or have taken pioglitazone HCl or other TZDs within 1 year of screening or were discontinued from TZD therapy due to lack of efficacy or clinical or laboratory signs of intolerance.
• The subject is a study site employee, or is an immediate family member (ie, spouse, parent, child, sibling) of a study site employee, involved in the conduct of this study.
• The subject has received or donated blood or blood products within 30 days preceding the beginning of the study or plans to donate blood during the study.

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Takeda Global Research & Development Center, Inc.

Overall Clinical Trial Officials and Contacts

Alfonso Perez, MD Study Director Takeda Global Research & Development Center, Inc.  

Overall Contact: Lisa Schwartz, RN 877-872-3700 lschwartz@tgrd.com

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00708175

Study ID Number: AD4833_402

ClinicalTrials.gov Identifier: NCT00708175

Health Authority: United States: Food and Drug Administration