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

Overview[ - collapse ][ - ]

Purpose The purpose of this study is to determine the effects of rosiglitazone on the bone in postmenopausal women with type 2 diabetes mellitus
ConditionDiabetes Mellitus, Type 2
InterventionDrug: Rosiglitazone
Drug: Metformin
PhasePhase 4
SponsorGlaxoSmithKline
Responsible PartyGlaxoSmithKline
ClinicalTrials.gov IdentifierNCT00679939
First ReceivedMay 15, 2008
Last UpdatedApril 5, 2013
Last verifiedApril 2013

Tracking Information[ + expand ][ + ]

First Received DateMay 15, 2008
Last Updated DateApril 5, 2013
Start DateApril 2008
Estimated Primary Completion DateSeptember 2010
Current Primary Outcome Measures
  • Adjusted Percent Change From Baseline in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) at Week 52 [Time Frame: Baseline and Week 52] [Designated as safety issue: Yes]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.
  • 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 [Time Frame: Baseline and Week 76+10 days] [Designated as safety issue: No]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.
  • 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 [Time Frame: Week 52+10 days and Week 76+10 days] [Designated as safety issue: No]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.
Current Secondary Outcome Measures
  • Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 [Time Frame: Baseline and Week 52] [Designated as safety issue: Yes]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.
  • 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 [Time Frame: Week 52 + 10 days and Week 76 + 10 days] [Designated as safety issue: No]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.
  • 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 [Time Frame: Week 52 + 30 days and Week 76 + 30 days] [Designated as safety issue: Yes]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.
  • Adjusted Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) at Week 52 and Week 76 [Time Frame: Baseline, Week 52, and Week 76] [Designated as safety issue: Yes]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.
  • Adjusted Percent Change in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) From Week 52 to Week 76 [Time Frame: Week 52 and Week 76] [Designated as safety issue: Yes]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.
  • Adjusted Percent Change From Baseline in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) at Week 52 and Week 76 [Time Frame: Baseline, Week 52, and Week 76] [Designated as safety issue: Yes]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.
  • Adjusted Percent Change in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) From Week 52 to Week 76 [Time Frame: Week 52 and Week 76] [Designated as safety issue: Yes]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.
  • Adjusted Percent Change From Baseline in 25-Hydroxyvitamin D (Vitamin D) at Week 52 and Week 76 [Time Frame: Baseline, Week 52, and Week 76] [Designated as safety issue: Yes]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.
  • Adjusted Percent Change in 25-Hydroxyvitamin D (Vitamin D) From Week 52 to Week 76 [Time Frame: Week 52 and Week 76] [Designated as safety issue: Yes]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.
  • Adjusted Percent Change From Baseline in Intact Parathyroid Hormone (PTH) at Week 52 and Week 76 [Time Frame: Baseline, Week 52, and Week 76] [Designated as safety issue: Yes]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.
  • Adjusted Percent Change in Intact Parathyroid Hormone (PTH) From Week 52 to Week 76 [Time Frame: Week 52 and Week 76] [Designated as safety issue: Yes]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.
  • Percent Change From Baseline in Serum Estradiol at Week 52 and Week 76 [Time Frame: Baseline, Week 52, and Week 76] [Designated as safety issue: Yes]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.
  • Percent Change in Serum Estradiol From Week 52 to Week 76 [Time Frame: Week 52 and Week 76] [Designated as safety issue: Yes]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.
  • Percent Change From Baseline in Total Testosterone at Week 52 and Week 76 [Time Frame: Baseline, Week 52, and Week 76] [Designated as safety issue: Yes]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.
  • Percent Change in Total Testosterone From Week 52 to Week 76 [Time Frame: Week 52 and Week 76] [Designated as safety issue: Yes]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.
  • Percent Change From Baseline in Free Testosterone at Week 52 and Week 76 [Time Frame: Baseline, Week 52, and Week 76] [Designated as safety issue: Yes]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.
  • Percent Change in Free Testosterone From Week 52 to Week 76 [Time Frame: Week 52 and Week 76] [Designated as safety issue: Yes]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.
  • Percent Change From Baseline in Sex Hormone Binding Globulin (SHBG) at Week 52 and Week 76 [Time Frame: Baseline, Week 52, and Week 76] [Designated as safety issue: Yes]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.
  • Percent Change in Sex Hormone Binding Globulin (SHBG) From Week 52 to Week 76 [Time Frame: Week 52 and Week 76] [Designated as safety issue: Yes]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.

Descriptive Information[ + expand ][ + ]

Brief TitleStudy In Postmenopausal Women With Type 2 Diabetes Looking At Approved Diabetes Drugs And How They Affect Bone Health
Official TitleA 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
Brief Summary
The purpose of this study is to determine the effects of rosiglitazone on the bone in
postmenopausal women with type 2 diabetes mellitus
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 4
Study DesignAllocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
ConditionDiabetes Mellitus, Type 2
InterventionDrug: Rosiglitazone
up to 8mg/day
Other Names:
RosiglitazoneDrug: Metformin
up to 2000mg/day
Study Arm (s)
  • Active Comparator: Arm 1 Treatment A
    rosiglitazone up to 8mg/day
  • Active Comparator: Arm 2 Treatment B
    metformin up to 2000mg/day

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment226
Estimated Completion DateSeptember 2010
Estimated Primary Completion DateMarch 2010
Eligibility Criteria
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
GenderFemale
Ages55 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesNot Provided

Administrative Information[ + expand ][ + ]

NCT Number NCT00679939
Other Study ID NumbersAVD111179
Has Data Monitoring CommitteeNo
Information Provided ByGlaxoSmithKline
Study SponsorGlaxoSmithKline
CollaboratorsNot Provided
Investigators Study Director: GSK Clinical Trials GlaxoSmithKline
Verification DateApril 2013