Efficacy of Pioglitazone on Bone Metabolism in Postmenopausal Women With Impaired Fasting Glucose.

Condition(s) targeted: Bone Metabolism

Intervention: Pioglitazone (Drug); Placebo (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Takeda Global Research & Development Center, Inc.

Official(s) and/or principal investigator(s):
VP Clinical Science Strategy, Study Director, Affiliation: Takeda Global Research & Development Center, Inc.

Overall contact:
Takeda Study Registration Call Center, Phone: 800-778-2860, Email: medicalinformation@tpna.com

The purpose of this study is to evaluate the effect of pioglitazone HCL on bone metabolism in postmenopausal women with impaired fasting glucose.

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

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

Primary outcome: Percent change from baseline to 12 months in bone mineral density in the total proximal femur by dual-energy x-ray absorptiometry (DXA).

Secondary outcome: Percent change from 12 months to 18 months in bone mineral density in the total proximal femur by dual-energy x-ray absorptiometry (DXA).

Detailed description: The World Health Organization has estimated that 30% of all women aged over 50 years (postmenopausal) have osteoporosis according to a definition of Bone Mineral Density at any site being more than 2. 5 standard deviations below the mean for young healthy adult women.

A known risk factor for development of osteoporosis and fracture is diabetes mellitus, with correlations to duration of disease and poor glycemic control.

Pioglitazone is a thiazolidinedione developed by Takeda Pharmaceuticals for the treatment of type 2 diabetes. Preclinical studies to date on the bone effects of thiazolidinediones have not clearly identified a mechanism of bone loss. While there is evidence of increased bone fractures in postmenopausal diabetic females treated with a thiazolidinedione, the mechanism is not known. Initial studies with thiazolidinediones in humans have focused on short term exposure (12 to 14 weeks) and non-diabetic females. These studies have shown acute changes in circulating bone markers and bone density, but have been questioned because they may not represent bone metabolism in states of abnormal glucose metabolism. Impaired glucose tolerance has been identified not only as a risk factor for developing type 2 diabetes, but also at higher risk for known complications of diabetes. Examination of the effect of thiazolidinediones on bone metabolism in IGT patients will provide data in patients with abnormal glucose tolerance, but without the potential confounding effects of oral hypoglycemic medications to treat type 2 diabetes.

The primary objective of this study is to evaluate the effect of pioglitazone on bone mass and metabolism in postmenopausal women with impaired fasting glucose or impaired glucose tolerance. Total participation time in this study is approximately 1 year and six months.

Minimum age: N/A. Maximum age: 70 Years. Gender(s): Female.

Criteria:

Inclusion Criteria:

- Is female and has not experienced menses for at least 5 years.

- Has a Fasting Plasma Glucose level greater than or equal to 100 and less than 126

mg/dL or a 2-hour post-oral glucose tolerance test greater than or equal to 140 and less than or equal to 199 mg/dL at Screening.

- Has a body mass index greater than or equal to 16 and less than or equal to 40 kg/m2

and weighs less than 300 pounds (approximately 136 kilograms).

- Agrees to take daily supplements of Vitamin D (a minimum of 800 IU daily) and calcium

(a minimum of 1000 mg daily) during the treatment and wash-out periods.

- Has clinical laboratory evaluations (including clinical chemistry, 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.

- Is in good health as determined by the physician (ie, via medical history and physical

examination) at Screening.

Exclusion Criteria:

- Has a fasting triglyceride level greater than 500 mg/dL.

- Has a hemoglobinopathy causing anemia or interfering with glycosylated hemoglobin

assays.

- Has an alanine transaminase level greater than or equal to 2. 5 times the upper limit

of normal, active liver disease or jaundice.

- Has Vitamin D (25-OH-D) less than 20 ng/mL.

- Has Baseline Bone Mineral Density defined as a T-score less than -2. 0 at the total

hip, spine, or femoral neck based on Caucasian reference values.

- Has unexplained microscopic or macroscopic hematuria confirmed by repeat testing.

- Has any of the following disorders:

- Rheumatoid Arthritis

- Thyroid (uncontrolled on thyroid replacement therapy), parathyroid, pituitary,

nutritional, inflammatory, gastrointestinal, autoimmune, or renal or other disease known to affect bone metabolism.

- A personal history of kidney stones.

- Has a clinical history after age 45 of wrist, hip, or leg fractures.

- Has a history of more than 1 asymptomatic vertebral deformity or any vertebral

deformity attributed to osteoporosis.

- Has a known history of drug abuse (defined as illicit drug use) or a known history of

alcohol abuse within 2 years of Screening.

- Has signs and/or symptoms of heart failure.

- Is currently 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.

- 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.

- 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.

- Has a history of breast cancer.

- Is taking or has ever taken pioglitazone or other Thiazolidinediones.

- Has received or donated blood or blood products within 30 days preceding the Screening

visit or plans to donate blood during the study.

- 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:

- gemfibrozil

- rifampicin

- systemic glucocorticoids and topical glucocorticoids

- immunosuppressors

- anti-epileptic agents

- proton pump inhibitors

- selective serotonin reuptake inhibitors

- lithium

- bisphosphonates

- systemic fluoride treatment, parathyroid hormone analog and aromatase inhibitors

- systemic estrogen therapy

- tamoxifen and raloxifene

- anti-diabetic medications

Takeda Study Registration Call Center, Phone: 800-778-2860, Email: medicalinformation@tpna.com

Walnut Creek, California, United States; Recruiting

Lakewood, Colorado, United States; Recruiting

Jupiter, Florida, United States; Recruiting

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Chicago, Illinois, United States; Recruiting

Bethesda, Maryland, United States; Recruiting

Detroit, Michigan, United States; Recruiting

Omaha, Nebraska, United States; Recruiting

Albuquerque, New Mexico, United States; Recruiting

Mineola, New York, United States; Recruiting

West Haverstraw, New York, United States; Recruiting

Cincinnati, Ohio, United States; Recruiting

Portland, Oregon, United States; Recruiting

Denton, Texas, United States; Recruiting

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