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

Osteoporosis, Postmenopausal Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01457950
• Other study ID #: 114163
• Status: Completed
• Phase: Phase 3
• First received: October 20, 2011
• Last updated: April 17, 2014
• Start date: November 2011
• Est. completion date: June 2013

Study information

• Verified date: February 2014
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 135
• Est. completion date: June 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 60 Years to 90 Years

Eligibility

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)

Study Design

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

Related Conditions & MeSH terms

• Osteoporosis
• Osteoporosis, Postmenopausal

Intervention

Drug:
• denosumab
double-blind phase: 60mg subcutaneous injection, single dose
• placebo
double-blind phase: placebo subcutaneous injection, single dose
• open-label denosumab
open-label phase: 60mg subcutaneous injection, single dose

Locations

Country	Name	City	State
Korea, Republic of	GSK Investigational Site	Busan
Korea, Republic of	GSK Investigational Site	Daegu
Korea, Republic of	GSK Investigational Site	Gwangju
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	songpa-gu, Seoul
Korea, Republic of	GSK Investigational Site	Suwon

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mean Percent Change From Baseline in Lumbar Spine BMD at Month 12 for Participants Previously Randomized to Denosumab	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.	Baseline and Month 12	No
Other	Mean Percent Change From Month 6 in Lumbar Spine BMD at Month 12 for Participants Previously Randomized to Placebo	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.	Month 6 and Month 12	No
Other	Mean Percent Change From Baseline in Total Hip, Femoral Neck, and Trochanter BMD at Month 12 for Participants Previously Randomized to Denosumab	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.	Baseline and Month 12	No
Other	Mean Percent Change From Month 6 in Total Hip, Femoral Neck, and Trochanter BMD at Month 12 for Participants Previously Randomized to Placebo	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.	Month 6 and Month 12	No
Other	Median Percent Change From Baseline in s-CTX and s-P1NP Biomarkers at Month 12 for Participants Previously Randomized to Denosumab	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.	Baseline and Month 12	No
Other	Median Percent Change From Month 6 in s-CTX and s-P1NP Biomarkers at Month 12 for Participants Previously Randomized to Placebo	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.	Month 6 and Month 12	No
Other	Number of Participants With Any Adverse Events (AE) or Any Serious Adverse Events (SAE) During the Open-Label Extension Phase	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.	From Month 6 to Month 12	No
Other	Change From Baseline in Albumin/Globulin Ratio and Blood Urea Nitrogen (BUN)/Creatinine Ratio at Month 12	Change from Baseline was calculated as the Month 12 value minus the Baseline value.	Baseline and Month 12	No
Other	Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin and Total Protein at Month 12	Change from Baseline was calculated as the Month 12 value minus the Baseline value.	Baseline and Month 12	No
Other	Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Month 12	Change from Baseline was calculated as the Month 12 value minus the Baseline value.	Baseline and Month 12	No
Other	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Platelet Count and White Blood Cell Count at Month 12	Change from Baseline was calculated as the Month 12 value minus the Baseline value.	Baseline and Month 12	No
Other	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine and Uric Acid at Month 12	Change from Baseline was calculated as the Month 12 value minus the Baseline value.	Baseline and Month 12	No
Other	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	Change from Baseline was calculated as the Month 12 value minus the Baseline value.	Baseline and Month 12	No
Other	Change From Baseline in Hematocrit at Month 12	Change from Baseline was calculated as the Month 12 value minus the Baseline value.	Baseline and Month 12	No
Other	Change From Baseline in Mean Corpuscle Hemoglobin at Month 12	Change from Baseline was calculated as the Month 12 value minus the Baseline value.	Baseline and Month 12	No
Other	Change From Baseline in Red Blood Cell Count at Month 12	Change from Baseline was calculated as the Month 12 value minus the Baseline value.	Baseline and Month 12	No
Other	Change From Baseline in Red Cell Distribution Width at Month 12	Change from Baseline was calculated as the Month 12 value minus the Baseline value.	Baseline and Month 12	No
Other	Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Month 12	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.	Baseline and Month 12	No
Other	Number of Participants With Positive and Negative Results for Anti-body Formation to Denosumab at Month 12	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.	Month 12	No
Primary	Mean Percent Change From Baseline in Lumbar Spine BMD at Month 6	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.	Baseline and Month 6	No
Secondary	Mean Percent Change From Baseline in Lumbar Spine BMD at Month 1	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.	Baseline and Month 1	No
Secondary	Mean Percent Change From Baseline in Total Hip, Femoral Neck, and Trochanter BMD at Month 1 and Month 6	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.	Baseline, Month 1 and Month 6	No
Secondary	Median Percent Change From Baseline in s-CTX and s-P1NP Biomarkers at Months 1, 3 and 6	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.	Baseline, Months 1, 3 and 6	No
Secondary	Number of Participants With Any Adverse Events (AE) or Any Serious Adverse Events (SAE)	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.	From Baseline up to Month 6	No
Secondary	Change From Baseline in Albumin/Globulin Ratio and Blood Urea Nitrogen (BUN)/Creatinine Ratio at Month 6	Change from Baseline was calculated as the Month 6 value minus the Baseline value.	Baseline and Month 6	No
Secondary	Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin and Total Protein at Month 6	Change from Baseline was calculated as the Month 6 value minus the Baseline value.	Baseline and Month 6	No
Secondary	Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Month 6	Change from Baseline was calculated as the Month 6 value minus the Baseline value.	Baseline and Month 6	No
Secondary	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Platelet Count and White Blood Cell Count at Month 6	Change from Baseline was calculated as the Month 6 value minus the Baseline value.	Baseline and Month 6	No
Secondary	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine and Uric Acid at Month 6	Change from Baseline was calculated as the Month 6 value minus the Baseline value.	Baseline and Month 6	No
Secondary	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	Change from Baseline was calculated as the Month 6 value minus the Baseline value.	Baseline and Month 6	No
Secondary	Change From Baseline in Hematocrit at Month 6	Change from Baseline was calculated as the Month 6 value minus the Baseline value.	Baseline and Month 6	No
Secondary	Change From Baseline in Mean Corpuscle Hemoglobin at Month 6	Change from Baseline was calculated as the Month 6 value minus the Baseline value.	Baseline and Month 6	No
Secondary	Change From Baseline in Mean Corpuscular Volume at Month 6	Change from Baseline was calculated as the Month 6 value minus the Baseline value.	Baseline and Month 6	No
Secondary	Change From Baseline in Red Blood Cell Count at Month 6	Change from Baseline was calculated as the Month 6 value minus the Baseline value.	Baseline and Month 6	No
Secondary	Change From Baseline in Red Cell Distribution Width at Month 6	Change from Baseline was calculated as the Month 6 value minus the Baseline value.	Baseline and Month 6	No
Secondary	Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Month 6	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.	Baseline and Month 6	No
Secondary	Number of Participants With Positive and Negative Results for Anti-body Formation to Denosumab	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.	Month 6	No