Study In Postmenopausal Women With Type 2 Diabetes Looking At Approved Diabetes Drugs And How They Affect Bone Health

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A 52 Week Randomized, Double-Blind, Multicenter, Mechanistic Study With a 24 Week Open-Label Follow-Up to Evaluate the Effect of AVANDIA TM on Bone in Postmenopausal Women With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00679939
• Other study ID #: AVD111179
• Status: Completed
• Phase: Phase 4
• First received: May 15, 2008
• Last updated: March 19, 2018
• Start date: April 21, 2008
• Est. completion date: September 16, 2010

Study information

• Verified date: March 2018
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the effects of rosiglitazone on the bone in postmenopausal women with type 2 diabetes mellitus

Recruitment information / eligibility

• Status: Completed
• Enrollment: 226
• Est. completion date: September 16, 2010
• Est. primary completion date: September 16, 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 55 Years to 80 Years

Eligibility

Inclusion Criteria:

• Female, >55 to <80 years

• >5 years menopausal

• Type 2 Diabetes Mellitus (T2DM) diagnosis according to American Diabetes Association (ADA), American Association of Clinical Endocrinologists (AACE), Canadian Diabetes Association (CDA), World Health Organization/International Diabetes Federation (WHO/IDF)

• Drug-naïve (HbA1c < or = 9.0%); OR Prior monotherapy, submaximal doses of metformin (< or = 1000mg Metformin), sulfonylureas (< or = 5mg Glyburide, < or = 10mg Glipizide or < or = 8mg glimepiride) or full dose Januvia (100mg) (HbA1c < or = 8.5%); OR Prior monotherapy, > submaximal doses of metformin (>1000mg) or sulfonylureas (>5mg Glyburide, >10mg Glipizide or >8mg glimepiride) (HbA1c < or = 7.0%)

• Weighs <300 lbs (136.4 kg)

• Two or more vertebra (L1-L4) suitable for BMD measurement by dual x-ray absorptiometry (DXA)

• Absolute BMD value consistent with T-score >-2.5 at femoral neck, lumbar spine and total hip

Exclusion Criteria:

• Type 1 Diabetes Mellitus (T1DM) or history of diabetic ketoacidosis (DKA)

• Renal or hepatic disease (clinically significant)

• Hepatocellular reaction, severe edema, or medically serious fluid event associated with thiazolidinedione (TZD)

• Recent (<6mos) history or clinical intervention for angina or myocardial infarction or is taking nitrates

• Any stage of heart failure, i.e. New York Heart Association (NYHA) class I-IV

• Systolic BP >160mmHg or diastolic BP >90mmHg while on antihypertensive

• Hypersensitivity to TZDs, biguanides

• Prior treatment with two or more oral anti-diabetic (OAD) agents

• Bilateral hip replacements

• Concurrent diseases affecting bone metabolism

• Active malabsorption syndrome

• Serum calcium outside the central lab reference range

• Thyroid replacement therapy, serum thyroid stimulating hormone (TSH) must be within range

• Vitamin D deficiency

• Previous treatment with: strontium, intravenous (IV) bisphosphonate, fluoride, hormones, calcineurin inhibitors or methotrexate

• Chronic systemic corticosteroid [e.g. glucocorticoid, mineralocorticoid] treatment of no more than two intra-articular injections within the past year or use of oral parenteral, or long-term, high-dose inhaled corticosteroids

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Rosiglitazone
up to 8mg/day
• Metformin
up to 2000mg/day

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Canada	GSK Investigational Site	Brampton	Ontario
Canada	GSK Investigational Site	Granby	Quebec
Canada	GSK Investigational Site	Vancouver	British Columbia
Estonia	GSK Investigational Site	Tallin
Estonia	GSK Investigational Site	Tallinn
Mexico	GSK Investigational Site	Cuernavaca	Morelos
Mexico	GSK Investigational Site	Durango
Mexico	GSK Investigational Site	Mérida	Yucatán
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Pakistan	GSK Investigational Site	Lahore
Philippines	GSK Investigational Site	Manila
Philippines	GSK Investigational Site	Marikina City
Spain	GSK Investigational Site	Alicante
Spain	GSK Investigational Site	Benidorm/Alicante
Spain	GSK Investigational Site	Granada
Spain	GSK Investigational Site	Granada
Spain	GSK Investigational Site	Petrer
United States	GSK Investigational Site	Albuquerque	New Mexico
United States	GSK Investigational Site	Albuquerque	New Mexico
United States	GSK Investigational Site	Columbia	South Carolina
United States	GSK Investigational Site	Columbia	South Carolina
United States	GSK Investigational Site	East Syracuse	New York
United States	GSK Investigational Site	Huntington Park	California
United States	GSK Investigational Site	Kingsport	Tennessee
United States	GSK Investigational Site	Kingston	New York
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Lexington	Kentucky
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	Slidell	Louisiana
United States	GSK Investigational Site	Torrance	California
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Vista	California
United States	GSK Investigational Site	Wenatchee	Washington

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Estonia,  Mexico,  Pakistan,  Philippines,  Spain, 

References & Publications (1)

Fitzpatrick LA, Bilezikian JP, Wooddell M, Paul G, Kolatkar NS, Nino AJ, Miller CG, Bogado CE, Arnaud CD, Cobitz AR. Mechanism of action study to evaluate the effect of rosiglitazone on bone in postmenopausal women with type 2 diabetes mellitus: rationale, study design and baseline characteristics. J Drug Assess. 2011 Dec 16;1(1):11-9. doi: 10.3109/21556660.2011.641703. eCollection 2012. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percent Change in Percentage of Free Estradiol From Week 52 to Week 76	Free estradiol levels were measured as a percentage of serum estrogen from blood samples. Free estradiol is the amount of estrogen available to the body for use. Percent change was based on log-transformed data.	Week 52 and Week 76
Other	Percent Change in Free Estradiol From Week 52 to Week 76	Free estradiol levels were measured in picomoles per Liter (pmol/L) from blood samples. Free estrodial is the amount of estrogen available to the body for use. Change was based on log-transformed data.	Week 52 and Week 76
Primary	Adjusted Percent Change From Baseline in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) at Week 52	FN BMD (measured in grams per centimeters squared [g/cm^2]) was measured by DXA. Bone mineral density is calculated as the mineral content of a bone divided by the area of the bone. DXA is the principal technique used for measuring BMD. Percent change from Baseline at Week 52 was calculated as (BMD at Week 52 minus BMD at Baseline)/BMD at Baseline x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Change in FN BMD at Week 52 was only analyzed within the Rosiglitazone arm.	Baseline and Week 52
Primary	Adjusted Percent Change From Baseline in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) at Week 76+10 Days	FN BMD (measured in grams per centimeters squared [g/cm^2]) was measured by DXA. Bone mineral density is calculated as the mineral content of a bone divided by the area of the bone. DXA is the principal technique used for measuring BMD. Percent change from Baseline at Week 76+10 days was calculated as (BMD at Week 76+10 days minus BMD at Baseline)/BMD at Baseline x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.	Baseline and Week 76+10 days
Primary	Adjusted Percent Change in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) From Week 52 +10 Days to Week 76+10 Days	FN BMD (measured in grams per centimeters squared [g/cm^2]) was measured by DXA. Bone mineral density is calculated as the mineral content of a bone divided by the area of the bone. DXA is the principal technique used for measuring BMD. Percent change from Week 52+10 days to Week 76+10 days was calculated as (BMD at Week 76+10 days minus BMD at Week 52+10 days)/BMD at Week 52+10 days x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.	Week 52+10 days and Week 76+10 days
Secondary	Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52	BMD (measured in grams per centimeters squared [g/cm^2]) was measured by DXA. Percent change from Baseline at Week 52 was calculated as (BMD at Week 52 minus BMD at Baseline)/BMD at Baseline x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.	Baseline and Week 52
Secondary	Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA From Week 52+10 Days to Week 76 + 10 Days	BMD (measured in grams per centimeters squared [g/cm^2]) was measured by DXA. Percent change from Week 52 + 10 days toat Week 76 + 10 days was calculated as (BMD at Week 76 + 10 days minus BMD at Week 52 + 10 days)/BMD at Week 52 + 10 days x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.	Week 52 + 10 days and Week 76 + 10 days
Secondary	Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA From Week 52+30 Days to Week 76 + 30 Days	BMD (measured in grams per centimeters squared [g/cm^2]) was measured by DXA. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (BMD at Week 76 + 30 days minus BMD at Week 52 + 30 days)/BMD at Week 52 + 30 days x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.	Week 52 + 30 days and Week 76 + 30 days
Secondary	Adjusted Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) at Week 52 and Week 76	BSAP and P1NP levels were measured in micrograms per liter (mcg/L) from blood samples. BSAP and P1NP are indicators of bone buildup or formation. GM, geometric mean; SE, standard error. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.	Baseline, Week 52, and Week 76
Secondary	Adjusted Percent Change in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) From Week 52 to Week 76	BSAP and P1NP levels were measured in micrograms per liter (mcg/L) from blood samples. BSAP and P1NP are indicators of bone buildup or formation. GM, geometric mean; SE, standard error. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.	Week 52 and Week 76
Secondary	Adjusted Percent Change From Baseline in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) at Week 52 and Week 76	CTX levels were measured in picograms per milliliter (pg/ml) from blood samples. CTX is an indicator of bone break down or resorption. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.	Baseline, Week 52, and Week 76
Secondary	Adjusted Percent Change in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) From Week 52 to Week 76	CTX levels were measured in picograms per milliliter (pg/ml) from blood samples. CTX is an indicator of bone break down or resorption. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.	Week 52 and Week 76
Secondary	Adjusted Percent Change From Baseline in 25-Hydroxyvitamin D (Vitamin D) at Week 52 and Week 76	Vitamin D levels were measured in nanomoles per Liter (nmol/L) from blood samples. Vitamin D is required for good bone health. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.	Baseline, Week 52, and Week 76
Secondary	Adjusted Percent Change in 25-Hydroxyvitamin D (Vitamin D) From Week 52 to Week 76	Vitamin D levels were measured in nanomoles per Liter (nmol/L) from blood samples. Vitamin D is required for good bone health. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.	Week 52 and Week 76
Secondary	Adjusted Percent Change From Baseline in Intact Parathyroid Hormone (PTH) at Week 52 and Week 76	Intact PTH levels were measured in nanograms per Liter (ng/L) from blood samples. Intact PTH is the amount of PTH circulating in the blood and influences bone health. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.	Baseline, Week 52, and Week 76
Secondary	Adjusted Percent Change in Intact Parathyroid Hormone (PTH) From Week 52 to Week 76	Intact PTH levels were measured in nanograms per Liter (ng/L) from blood samples. Intact PTH is the amount of PTH circulating in the blood and influences bone health. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.	Week 52 and Week 76
Secondary	Percent Change From Baseline in Serum Estradiol at Week 52 and Week 76	Serum estradiol levels were measured in picomoles per Liter (pmol/L) from blood samples. Estradiol is one form of the female sex hormone estrogen and influences bone health. Percent change from baseline was based on log-transformed data.	Baseline, Week 52, and Week 76
Secondary	Percent Change in Serum Estradiol From Week 52 to Week 76	Serum estradiol levels were measured in picomoles per Liter (pmol/L) from blood samples. Estradiol is one form of the female sex hormone estrogen and influences bone health. Percent change from baseline was based on log-transformed data.	Week 52 and Week 76
Secondary	Percent Change From Baseline in Total Testosterone at Week 52 and Week 76	Total testosterone levels were measured in nanomoles per Liter (nmol/L) from blood samples. Testosterone is a male sex hormone and influences bone health; total testosterone is the entire amount circulating in blood. Percent change from baseline was based on log-transformed data.	Baseline, Week 52, and Week 76
Secondary	Percent Change in Total Testosterone From Week 52 to Week 76	Total testosterone levels were measured in nanomoles per Liter (nmol/L) from blood samples. Testosterone is a male sex hormone and influences bone health; total testosterone is the entire amount circulating in blood. Percent change from baseline was based on log-transformed data.	Week 52 and Week 76
Secondary	Percent Change From Baseline in Free Testosterone at Week 52 and Week 76	Free testosterone levels were measured as a percentage of total testosterone from blood samples. Free testosterone is the amount of testosterone available to the body for use. Percent change from baseline was based on log-transformed data.	Baseline, Week 52, and Week 76
Secondary	Percent Change in Free Testosterone From Week 52 to Week 76	Free testosterone levels were measured as a percentage of total testosterone from blood samples. Free testosterone is the amount of testosterone available to the body for use. Percent change from baseline was based on log-transformed data.	Week 52 and Week 76
Secondary	Percent Change From Baseline in Sex Hormone Binding Globulin (SHBG) at Week 52 and Week 76	SHBG levels were measured in nanomoles per liter (nmol/L) from blood samples. SHBG binds to estradiol and testosterone and influences the amount of estradiol or testosterone available to the body for use. Percent change from baseline was based on log-transformed data.	Baseline, Week 52, and Week 76
Secondary	Percent Change in Sex Hormone Binding Globulin (SHBG) From Week 52 to Week 76	SHBG levels were measured in nanomoles per liter (nmol/L) from blood samples. SHBG binds to estradiol and testosterone and influences the amount of estradiol or testosterone available to the body for use. Percent change from baseline was based on log-transformed data.	Week 52 and Week 76

External Links

•   Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.