Clinical trial NCT01457950: A Study in Korean Postmenopausal Women With Osteoporosis to Evaluate the Efficacy and Safety of Denosumab
Official title: A Six Month Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study With a Six Month Open-Label Extension to Evaluate the Efficacy and Safety of Denosumab in Korean Postmenopausal Women With Osteoporosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoporosis, Postmenopausal
Keywords: denosumab
Republic of Korea
dual energy x-ray absorptiometry
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-10-24
Enrollment: 135
Sex: FEMALE
Minimum age (years): 60
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if denosumab is effective in increasing bone mineral density at the lumbar spine in Korean postmenopausal women with osteoporosis.


Eligibility criteria: Inclusion Criteria:

* Ambulatory Korean postmenopausal women with osteoporosis
* greater than 5 years postmenopausal
* aged 60 to 90 years old
* absolute bone mineral density value consistent with a T-score less than -2.5 and greater than or equal to - 4.0 at the either the lumbar spine or total hip, as measured by dual energy x-ray absorptiometry. Subjects with a T-score less than -4.0 are at very high risk for fracture and will be excluded.

Exclusion Criteria:

* previous or current metabolic bone disease, Paget's or Cushing's disease, or hyperprolactinemia
* current hypo- or hyperparathyroidism or hypo- or hyperthyroidism unless on stable thyroid replacement therapy and TSH level meets criteria
* rheumatoid arthritis
* cirrhosis of the liver or unstable liver disease or ALT or AST greater than or equal to 2.0 times the upper limit of normal, or alkaline phosphatase and bilirubin greater than or equal to 1.5 times the upper limit of normal
* medications used to treat osteoporosis, defined for type and duration of use, and including IV and oral bisphosphonates
* medications that affect bone metabolism including parathyroid hormone or derivatives; anabolic steroids or testosterone; glucocorticosteroids; systemic hormone replacement therapy; selective estrogen receptor modulators; tibolone, calcitonin, and calcitriol or vitamin D derivatives; other bone active drugs including anticonvulsives (but not benzodiazepines) and heparin; chronic systemic ketoconazole, androgens, ACTH, cinacalcet, aluminum, lithium, protease inhibitors, methotrexate, and gonadotropin-releasing hormone agonists
* malignancy within 5 years except certain resected types
* malabsorption syndrome or gastrointestinal disorders associated with malabsorption
* abnormal calcium level
* vitamin D deficiency
* any laboratory abnormality that will prevent the subject from completing the study or interfere with interpretation of study results
* severe renal impairment or on dialysis
* impaired immune system or subject is taking immunosuppressants
* oral or dental conditions including current or past history of osteomyelitis or osteonecrosis of the jaw; active dental or jaw condition with requires oral surgery; planned invasive dental procedure; un-healed dental or oral surgery
* any disorder that compromises the ability of the subject to give written informed consent or to comply with study procedures
* any physical or psychiatric disorder that will prevent the subject from completing the study or interferes with study results
* known to have tested positive for HIV
* less than two lumbar vertebrae evaluable for DXA measurements
* height, weight, or girth that may preclude accurate DXA measurements
* drug or alcohol abuse within 12 months that interferes with understanding or completing the study
* known sensitivity to mammalian cell-derived drug products
* use of an investigational drug or device within 30 days of enrollment or currently receiving other investigational agent(s)

Primary outcomes:
measure: Mean Percent Change From Baseline in Lumbar Spine BMD at Month 6
timeFrame: Baseline and Month 6
Secondary outcomes:
measure: Mean Percent Change From Baseline in Lumbar Spine BMD at Month 1
timeFrame: Baseline and Month 1
measure: Mean Percent Change From Baseline in Total Hip, Femoral Neck, and Trochanter BMD at Month 1 and Month 6
timeFrame: Baseline, Month 1 and Month 6
measure: Median Percent Change From Baseline in s-CTX and s-P1NP Biomarkers at Months 1, 3 and 6
timeFrame: Baseline, Months 1, 3 and 6
measure: Number of Participants With Any Adverse Events (AE) or Any Serious Adverse Events (SAE)
timeFrame: From Baseline up to Month 6
measure: Change From Baseline in Albumin/Globulin Ratio and Blood Urea Nitrogen (BUN)/Creatinine Ratio at Month 6
timeFrame: Baseline and Month 6
measure: Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin and Total Protein at Month 6
timeFrame: Baseline and Month 6
measure: Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Month 6
timeFrame: Baseline and Month 6
measure: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Platelet Count and White Blood Cell Count at Month 6
timeFrame: Baseline and Month 6
measure: Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine and Uric Acid at Month 6
timeFrame: Baseline and Month 6
measure: Change From Baseline in Calcium Corrected, Calcium, Chloride, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Triglycerides, Urea/BUN, Very Low Density Lipoproteins (VLDL) Cholesterol Calculation at Month 6
timeFrame: Baseline and Month 6
measure: Change From Baseline in Hematocrit at Month 6
timeFrame: Baseline and Month 6
measure: Change From Baseline in Mean Corpuscle Hemoglobin at Month 6
timeFrame: Baseline and Month 6
measure: Change From Baseline in Mean Corpuscular Volume at Month 6
timeFrame: Baseline and Month 6
measure: Change From Baseline in Red Blood Cell Count at Month 6
timeFrame: Baseline and Month 6
measure: Change From Baseline in Red Cell Distribution Width at Month 6
timeFrame: Baseline and Month 6
measure: Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Month 6
timeFrame: Baseline and Month 6
measure: Number of Participants With Positive and Negative Results for Anti-body Formation to Denosumab
timeFrame: Month 6
Other outcomes:
measure: Mean Percent Change From Baseline in Lumbar Spine BMD at Month 12 for Participants Previously Randomized to Denosumab
timeFrame: Baseline and Month 12
measure: Mean Percent Change From Month 6 in Lumbar Spine BMD at Month 12 for Participants Previously Randomized to Placebo
timeFrame: Month 6 and Month 12
measure: Mean Percent Change From Baseline in Total Hip, Femoral Neck, and Trochanter BMD at Month 12 for Participants Previously Randomized to Denosumab
timeFrame: Baseline and Month 12
measure: Mean Percent Change From Month 6 in Total Hip, Femoral Neck, and Trochanter BMD at Month 12 for Participants Previously Randomized to Placebo
timeFrame: Month 6 and Month 12
measure: Median Percent Change From Baseline in s-CTX and s-P1NP Biomarkers at Month 12 for Participants Previously Randomized to Denosumab
timeFrame: Baseline and Month 12
measure: Median Percent Change From Month 6 in s-CTX and s-P1NP Biomarkers at Month 12 for Participants Previously Randomized to Placebo
timeFrame: Month 6 and Month 12
measure: Number of Participants With Any Adverse Events (AE) or Any Serious Adverse Events (SAE) During the Open-Label Extension Phase
timeFrame: From Month 6 to Month 12
measure: Change From Baseline in Albumin/Globulin Ratio and Blood Urea Nitrogen (BUN)/Creatinine Ratio at Month 12
timeFrame: Baseline and Month 12
measure: Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin and Total Protein at Month 12
timeFrame: Baseline and Month 12
measure: Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Month 12
timeFrame: Baseline and Month 12
measure: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Platelet Count and White Blood Cell Count at Month 12
timeFrame: Baseline and Month 12
measure: Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine and Uric Acid at Month 12
timeFrame: Baseline and Month 12
measure: Change From Baseline in Calcium Corrected, Calcium, Chloride, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Triglycerides, Urea/BUN, Very Low Density Lipoproteins (VLDL) Cholesterol Calculation at Month 12
timeFrame: Baseline and Month 12
measure: Change From Baseline in Hematocrit at Month 12
timeFrame: Baseline and Month 12
measure: Change From Baseline in Mean Corpuscle Hemoglobin at Month 12
timeFrame: Baseline and Month 12
measure: Change From Baseline in Red Blood Cell Count at Month 12
timeFrame: Baseline and Month 12
measure: Change From Baseline in Red Cell Distribution Width at Month 12
timeFrame: Baseline and Month 12
measure: Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Month 12
timeFrame: Baseline and Month 12
measure: Number of Participants With Positive and Negative Results for Anti-body Formation to Denosumab at Month 12
timeFrame: Month 12
Locations:
city: Busan
country: Korea, Republic of
facility: GSK Investigational Site
city: Daegu
country: Korea, Republic of
facility: GSK Investigational Site
city: Gwangju
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: songpa-gu, Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Suwon
country: Korea, Republic of
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: