A Study in Korean Postmenopausal Women With Osteoporosis to Evaluate the Efficacy and Safety of Denosumab

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01457950
First received: October 20, 2011
Last updated: April 17, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Osteoporosis, Postmenopausal
Drug: denosumab
Drug: placebo
Drug: open-label denosumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Mean Percent Change From Baseline in Lumbar Spine BMD at Month 6 [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    Mean percent change from Baseline in lumbar spine bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using the Analysis of Covariance (ANCOVA) model adjusting for treatment and Baseline BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Baseline=(measure at Month 6 - measure at Baseline) divided by the measure at Baseline * 100.


Secondary Outcome Measures:
  • Mean Percent Change From Baseline in Lumbar Spine BMD at Month 1 [ Time Frame: Baseline and Month 1 ] [ Designated as safety issue: No ]
    Mean percent change from Baseline in lumbar spine bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using Analysis of Covariance (ANCOVA) model adjusting for treatment and Baseline BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Baseline=(measure at Month 1 - measure at Baseline) divided by the measure at Baseline * 100.

  • Mean Percent Change From Baseline in Total Hip, Femoral Neck, and Trochanter BMD at Month 1 and Month 6 [ Time Frame: Baseline, Month 1 and Month 6 ] [ Designated as safety issue: No ]
    Mean percent change from Baseline in total hip, femoral neck, and trochanter bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using Analysis of Covarience (ANCOVA) model adjusting for treatment and Baseline BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Baseline=(measure at Month 1/6 - measure at Baseline) divided by the measure at Baseline * 100.

  • Median Percent Change From Baseline in s-CTX and s-P1NP Biomarkers at Months 1, 3 and 6 [ Time Frame: Baseline, Months 1, 3 and 6 ] [ Designated as safety issue: No ]
    Serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTx) I and Serum procollagen type I N propeptide s (s-PINP) are used as serum biomarkers of bone resorption in the assessment of osteoporosis and is measured in units of micrograms (µg)/liters (L). Percentage change from Baseline=(measure at post-Baseline - measure at Baseline) divided by measure at Baseline * 100.

  • Number of Participants With Any Adverse Events (AE) or Any Serious Adverse Events (SAE) [ Time Frame: From Baseline up to Month 6 ] [ Designated as safety issue: No ]
    An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.

  • Change From Baseline in Albumin/Globulin Ratio and Blood Urea Nitrogen (BUN)/Creatinine Ratio at Month 6 [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 6 value minus the Baseline value.

  • Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin and Total Protein at Month 6 [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 6 value minus the Baseline value.

  • Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Month 6 [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 6 value minus the Baseline value.

  • Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Platelet Count and White Blood Cell Count at Month 6 [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 6 value minus the Baseline value.

  • Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine and Uric Acid at Month 6 [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 6 value minus the Baseline value.

  • 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 [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 6 value minus the Baseline value.

  • Change From Baseline in Hematocrit at Month 6 [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 6 value minus the Baseline value.

  • Change From Baseline in Mean Corpuscle Hemoglobin at Month 6 [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 6 value minus the Baseline value.

  • Change From Baseline in Mean Corpuscular Volume at Month 6 [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 6 value minus the Baseline value.

  • Change From Baseline in Red Blood Cell Count at Month 6 [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 6 value minus the Baseline value.

  • Change From Baseline in Red Cell Distribution Width at Month 6 [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 6 value minus the Baseline value.

  • Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Month 6 [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    Vital Sign Changes from Baseline of potential clinical concern for Diastolic Blood Pressure (<50 or >120 Bits Per Minutes [bpm]), Systolic Blood Pressure (>170 Millimeters of Mercury [mmHg] or <100 mmHg) and Heart rate (>110 mmHg or <50 mmHg) are summarized. Change from Baseline was calculated as the Month 6 value minus the Baseline value.

  • Number of Participants With Positive and Negative Results for Anti-body Formation to Denosumab [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
    Number of participants with positive and negative results for both neutralizing antibodies to denosumab, and for binding antibodies to denosumab at Month 6 was summarized.


Other Outcome Measures:
  • Mean Percent Change From Baseline in Lumbar Spine BMD at Month 12 for Participants Previously Randomized to Denosumab [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    Mean percent change from Baseline in lumbar spine bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using Analysis of Covariance (ANCOVA) model adjusting for treatment and Baseline BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Baseline=(measure at Month 12 - measure at Baseline) divided by the measure at Baseline * 100.

  • Mean Percent Change From Month 6 in Lumbar Spine BMD at Month 12 for Participants Previously Randomized to Placebo [ Time Frame: Month 6 and Month 12 ] [ Designated as safety issue: No ]
    Mean percent change from Month 6 in lumbar spine bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using Analysis of Covariance (ANCOVA) model adjusting for treatment and Month 6 BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Month 6=(measure at Month 12 - measure at Month 6) divided by the measure at Month 6 * 100.

  • Mean Percent Change From Baseline in Total Hip, Femoral Neck, and Trochanter BMD at Month 12 for Participants Previously Randomized to Denosumab [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    Mean percent change from Baseline in total hip, femoral neck, and trochanter bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using Analysis of Covariance (ANCOVA) model adjusting for treatment and Baseline BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Baseline=(measure at Month 12 - measure at Baseline) divided by the measure at Baseline * 100.

  • Mean Percent Change From Month 6 in Total Hip, Femoral Neck, and Trochanter BMD at Month 12 for Participants Previously Randomized to Placebo [ Time Frame: Month 6 and Month 12 ] [ Designated as safety issue: No ]
    Mean percent change from Month 6 in total hip, femoral neck, and trochanter bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using Analysis of Covariance (ANCOVA) model adjusting for treatment and Month 6 BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Month 6=(measure at Month 12 - measure at Month 6) divided by the measure at Month 6 * 100.

  • Median Percent Change From Baseline in s-CTX and s-P1NP Biomarkers at Month 12 for Participants Previously Randomized to Denosumab [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    Serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTx) I and Serum procollagen type I N propeptide s (s-PINP) are used as serum biomarkers of bone resorption in the assessment of osteoporosis and is measured in units of micrograms (µg)/liters (L). Percentage change from Baseline=(measure at post-Baseline - measure at Baseline) divided by measure at Baseline * 100.

  • Median Percent Change From Month 6 in s-CTX and s-P1NP Biomarkers at Month 12 for Participants Previously Randomized to Placebo [ Time Frame: Month 6 and Month 12 ] [ Designated as safety issue: No ]
    Serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTx) I and Serum procollagen type I N propeptide s (s-PINP) are used as serum biomarkers of bone resorption in the assessment of osteoporosis and is measured in units of micrograms (µg)/liters (L). Percentage change from Month 6=(measure at Month 12 - measure at Month 6) divided by measure at Month 6 * 100.

  • Number of Participants With Any Adverse Events (AE) or Any Serious Adverse Events (SAE) During the Open-Label Extension Phase [ Time Frame: From Month 6 to Month 12 ] [ Designated as safety issue: No ]
    An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.

  • Change From Baseline in Albumin/Globulin Ratio and Blood Urea Nitrogen (BUN)/Creatinine Ratio at Month 12 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 12 value minus the Baseline value.

  • Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin and Total Protein at Month 12 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 12 value minus the Baseline value.

  • Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Month 12 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 12 value minus the Baseline value.

  • Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Platelet Count and White Blood Cell Count at Month 12 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 12 value minus the Baseline value.

  • Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine and Uric Acid at Month 12 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 12 value minus the Baseline value.

  • 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 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 12 value minus the Baseline value.

  • Change From Baseline in Hematocrit at Month 12 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 12 value minus the Baseline value.

  • Change From Baseline in Mean Corpuscle Hemoglobin at Month 12 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 12 value minus the Baseline value.

  • Change From Baseline in Red Blood Cell Count at Month 12 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 12 value minus the Baseline value.

  • Change From Baseline in Red Cell Distribution Width at Month 12 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    Change from Baseline was calculated as the Month 12 value minus the Baseline value.

  • Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Month 12 [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    Vital Sign Changes from Baseline of potential clinical concern for Diastolic Blood Pressure (<50 or >120 Bits Per Minutes [bpm]), Systolic Blood Pressure (>170 Millimeters of Mercury [mmHg] or <100 mmHg) and Heart rate (>110 mmHg or <50 mmHg) are summarized. Change from Baseline was calculated as the Month 12 value minus the Baseline value.

  • Number of Participants With Positive and Negative Results for Anti-body Formation to Denosumab at Month 12 [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    Number of participants with positive and negative results for both neutralizing antibodies to denosumab, and for binding antibodies to denosumab at Month 12 was summarized.


Enrollment: 135
Study Start Date: November 2011
Study Completion Date: June 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
denosumab 60mg subcutaneous injection, single dose at the start of the 6-month double-blind phase
Drug: denosumab
double-blind phase: 60mg subcutaneous injection, single dose
Placebo Comparator: Arm 2
placebo subcutaneous injection, single dose at the start of the 6-month double-blind phase
Drug: placebo
double-blind phase: placebo subcutaneous injection, single dose
Experimental: Arm 3
open-label phase follows the double-blind phase, denosumab 60mg subcutaneous injection, single dose at the start of the 6-month open-label phase
Drug: open-label denosumab
open-label phase: 60mg subcutaneous injection, single dose

  Eligibility

Ages Eligible for Study:   60 Years to 90 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01457950

Locations
Korea, Republic of
GSK Investigational Site
Busan, Korea, Republic of, 602-739
GSK Investigational Site
Daegu, Korea, Republic of
GSK Investigational Site
Gwangju, Korea, Republic of, 501-757
GSK Investigational Site
Seoul, Korea, Republic of, 100-380
GSK Investigational Site
Seoul, Korea, Republic of, 135-710
GSK Investigational Site
Seoul, Korea, Republic of, 120-752
GSK Investigational Site
Seoul, Korea, Republic of, 110-744
GSK Investigational Site
Seoul, Korea, Republic of, 137-701
GSK Investigational Site
songpa-gu, Seoul, Korea, Republic of, 138-736
GSK Investigational Site
Suwon, Korea, Republic of, 443-721
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01457950     History of Changes
Other Study ID Numbers: 114163
Study First Received: October 20, 2011
Results First Received: August 22, 2013
Last Updated: April 17, 2014
Health Authority: Korea: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
denosumab
Republic of Korea
dual energy x-ray absorptiometry

Additional relevant MeSH terms:
Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases

ClinicalTrials.gov processed this record on September 18, 2014