Osteoporosis, PostmenopausalPhase 3NCT02014467
Denosumab China Phase III Study
A Phase 3 study testing Denosumab, Elemental Calcium and Vitamin D in people with Osteoporosis, Postmenopausal, run by GlaxoSmithKline at 8 sites in China.
Trial summary
This study is to evaluate the efficacy and safety of denosumab 60 milligrams (mg) for 12 month treatment in Chinese postmenopausal women with osteoporosis at increased risk of fracture. Read more about this study
- Who is it for?
- Ages 60 to 90 years, women only
- Conditions the study is for
- Osteoporosis, Postmenopausal
- What is being tested?
- Denosumab, Elemental Calcium and Vitamin D
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 486 participants
- Where
- 8 sitesChina
- Study dates
- Jan 2014to Aug 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 90 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject is willing and able to provide written informed consent.
- Of Chinese origin - defined as being born in China, having four ethnic Chinese grandparents.
- Ambulatory woman between the age of 60 and 90 years, inclusive.
- The subject has a BMD absolute value consistent with a T-score<-2.5 and >-4.0 at either the lumbar spine or total hip.
- All subjects must have at least one of following additional the risk factors:
- history of fracture parental history of hip fracture increased bone turnover rate at screening (s-CTX >1.0 SD above the mean in healthy premenopausal women) low body weight (BMI≤19kg/m2) elderly (age≥70y) current smoker
- Postmenopausal defined as >5 years postmenopausal, which can be >5 years of spontaneous amenorrhea or >5 years post surgical bilateral oophorectomy. Use follicle stimulating hormone (FSH) levels >40 mIU/mL to confirm surgical postmenopausal status, where bilateral oophorectomy status is uncertain.
Who cannot join
- Bone/metabolic disease:
- Any metabolic bone disease, e.g., osteomalacia or osteogenesis imperfecta, which may interfere with the interpretation of the findings.
- Paget's disease Cushing's disease Hyperprolactinemia
- Current hyperparathyroidism or hypoparathyroidism by medical record
- Thyroid condition: Hyperthyroidism or hypothyroidism. Only subjects with hypothyroidism who are on stable thyroid hormone replacement therapy may be allowed per the following criteria:
- If TSH level is below normal range, subject is not eligible for the study. If TSH level is elevated (>5.5 μIU/mL and ≤10.0 μIU/mL), serum T4 should be measured.
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- If serum T4 is within normal range, subject is eligible. If serum T4 is outside of normal range, subject is not eligible for the study. If TSH level is > 10.0 μIU/mL, subject is not eligible.
- Rheumatoid arthritis
- Malignancy:
- Malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical or breast ductal carcinoma in situ) within the last 5years.
- Malabsorption syndrome: malabsorption syndrome or any gastrointestinal disorders associated with malabsorption, for example Crohn's Disease and chronic pancreatitis.
- Renal disease - severe renal impairment
- Liver disease:
- Cirrhosis of the liver Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). Chronic stable hepatitis B and C are acceptable if the subject otherwise meets study entry criteria (e.g., presence of hepatitis B surface antigen or positive Hepatitis C test result within 3 months of Screening).
- Drug or alcohol abuse: Evidence of alcohol or substance-abuse within the last 12 months which the investigator believes would interfere with understanding or completing the study.
- Biological abnormalities:
- 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 which, in the opinion of the investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results.
- Known to have tested positive for human immunodeficiency virus (HIV).
- Vitamin D deficiency: Vitamin D deficiency (25-(OH) vitamin D level <20 ng/mL). Vitamin D repletion will be permitted and after repletion subjects may be re-tested once for 25-(OH) vitamin D levels.
- Oral/Dental Conditions Prior history or current evidence of osteomyelitis or osteonecrosis of the jaw. Active dental or jaw condition which requires oral surgery. Planned invasive dental procedure. Non-healed dental or oral surgery.
- Concomitant Medications:
- Previous strontium or IV bisphosphonate: Administration of intravenous (IV) bisphosphonate, fluoride, or strontium for osteoporosis within the last 5 years.
- Oral bisphosphonate: Oral bisphosphonate treatment for osteoporosis:
- If used for ≥3 years cumulatively, subject is ineligible.
- If used for >3-months but <3 years cumulatively:
- If the last dose was <1 year before enrolment, subject is ineligible. If the last dose was ≥1 year before enrolment, subject is eligible. If used ≤3 months, cumulatively, subject is eligible.
- Bone metabolism drugs: Administration of any of the following treatments within the last 6 weeks:
- Parathyroid hormone (PTH) or PTH derivatives, e.g., teriparatide. Anabolic steroids or testosterone. Glucocorticosteroids (>5 mg prednisone equivalent per day for more than 10 days).
- Systemic hormone replacement therapy. Selective estrogen receptor modulators (SERMs), e.g., raloxifene Tibolone. Calcitonin. Calcitriol or vitamin D derivatives. Other bone active drugs including anti-convulsives (except benzodiazepines) and heparin.
- Chronic systemic ketoconazole, androgens, ACTH, cinacalcet, aluminum, lithium, protease inhibitors, methotrexate, gonadotropin-releasing hormone agonists.
- Investigational drug exposure: Currently enrolled in an investigational device or drug trial(s) or it has not been at least 30 days since the last study visit in an investigational device or drug trial(s), or subject is receiving other investigational agent(s).
- Sensitivity: Known sensitivity to mammalian cell-derived drug products.
- Clinically significant hypersensitivity to denosumab Abnormal laboratory values
- General: Any laboratory abnormality which, in the opinion of the investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results.
- Abnormal serum calcium: current hypocalcemia or hypercalcemia. Albumin adjusted serum calcium levels must be within normal limits of the central laboratory.
- Liver transaminases:
- Serum aspartate aminotransferase (AST) ≥2.0 x upper limits of normal (ULN). Serum alanine aminotransferase (ALT) ≥2.0 x ULN. Alkaline phosphatase and bilirubin ≥1.5 x ULN (isolated bilirubin ≥1.5 ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%.
- DXA measurements:
- Less than two lumbar vertebrae evaluable for DXA measurements. Height, weight, or girth which may preclude accurate DXA measurements.
- Subjects with a history of greater than 2 vertebral fractures.
- Subjects at very high risk of fracture who must be treated with active drugs in the opinion of investigator.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
China8 sites
GSK Investigational Site
Beijing, 100035
GSK Investigational Site
Beijing, 100050
GSK Investigational Site
Beijing, 100730
GSK Investigational Site
Chengdu, Sichuan, 610041
GSK Investigational Site
Chengdu, Sichuan, 610072
GSK Investigational Site
Chengdu, 610083
GSK Investigational Site
Shanghai, 200040
GSK Investigational Site
Shanghai, 200233
About this study
Official title: A Twelve-Month Randomized, Double-Blind, Placebo Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy and Safety of Denosumab in Chinese Postmenopausal Women With Osteoporosis at Increased Risk of Fracture
This study is to evaluate the efficacy and safety of denosumab 60 milligrams (mg) for 12 month treatment in Chinese postmenopausal women with osteoporosis at increased risk of fracture.
Read the detailed description
The aim of this Phase III, randomized, double-blind, placebo-controlled, parallel-group study is to evaluate the efficacy and safety of denosumab (DMAb) in Chinese postmenopausal women with osteoporosis at increased risk of fracture. The study design consists of two phases: Screening and 12-month Double-Blind treatment phase. Following the Screening phase, all eligible subjects will be randomized to receive Double-Blind DMAb (60 mg) or Placebo study medication in a 3:1 ratio. DMAb 60 mg and placebo will be administered as a single subcutaneous (SC) injection at the beginning of the Double-Blind phase and at 6 months following the initial dose. All subjects will receive daily supplementation of oral elemental calcium (at least 600 mg) and vitamin D (at least 400 International Units [IU]). The primary objective is to determine the effects of DMAb compared to placebo with respect to mean percent change in BMD at the lumbar spine, as measured by dual-energy x-ray absorptiometry (DXA), from Baseline to Month 12. Secondary objectives include the evaluation between the DMAb and placebo treatment groups: change in BMD: at the lumbar spine (Month 6), total hip (Months 6 and 12), femoral neck (Months 6 and 12) and trochanter (Months 6 and 12); and serum biomarkers of bone formation and resorption (Months 6 and 12). Clinical safety of denosumab will also be assessed in this population.
- Conditions
- Osteoporosis, Postmenopausal
- Being tested
- Denosumab, Placebo, Elemental Calcium, Vitamin D
- Medical subject headings
- Osteoporosis, Postmenopausal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabDrug
Injection
PlaceboDrug
Injection
Elemental CalciumDietary supplement
Oral, at least 600 mg
Vitamin DDietary supplement
Oral, at least 400 IU
| Study group | Role | What they receive |
|---|---|---|
| Denosumab 60mg | Experimental | injection Receives: Drug: Denosumab; Dietary Supplement: Elemental Calcium; Dietary Supplement: Vitamin D |
| Placebo | Placebo comparator | injection Receives: Drug: Placebo; Dietary Supplement: Elemental Calcium; Dietary Supplement: Vitamin D |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine at Month 12
Bone mineral density (BMD) is the amount of bone mineral in bone tissue. BMD scan was done using dual energy x-ray absorptiometry (DXA). It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calcuated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value. The analysis was performed by Analysis of Covariance (ANCOVA) model adjusted for treatment, region and Baseline BMD for the skeletal site under consideration as a continuous covariate for assessment. Region and treatment by region interaction was included in the model. Screening visit was considered as Baseline for BMD. For participants who withdrew early, the missing BMD assessments was estimated by the Last Observation Carried Forward (LOCF), provided the assessment was taken on or after at least one month on-therapy.
Measured: Baseline and Month 12
Secondary outcomes (27)
Percent Change From Baseline in BMD at the Lumbar Spine at Month 6
BMD is the amount of bone mineral in bone tissue. BMD scan was done using DXA. It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calculated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value. ANCOVA model adjusted for treatment, center/region and Baseline BMD for the skeletal site under consideration as a continuous covariate for assessment. Region and treatment by region interaction was included in the model. Screening visit was considered as baseline for BMD. For participants who withdrew early, the missing BMD assessments was estimated by the LOCF, provided the assessment was taken on or after at least one month on-therapy.
Measured: Baseline and Month 6
Percent Change From Baseline in BMD at the Total Hip at Month 6
BMD is the amount of bone mineral in bone tissue. BMD scan was done using DXA. It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calculated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value. ANCOVA model adjusted for treatment, center/region and Baseline BMD for the skeletal site under consideration as a continuous covariate for assessment. Region and treatment by region interaction was included in the model. Screening visit was considered as baseline for BMD. For participants who withdrew early, the missing BMD assessments was estimated by the LOCF, provided the assessment was taken on or after at least one month on-therapy.
Measured: Baseline and Month 6
Percent Change From Baseline in BMD at the Femoral Neck at Month 6
BMD is the amount of bone mineral in bone tissue. BMD scan was done using DXA. It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calculated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value. ANCOVA model adjusted for treatment, center/region and Baseline BMD for the skeletal site under consideration as a continuous covariate for assessment. Region and treatment by region interaction was included in the model. Screening visit was considered as baseline for BMD. For participants who withdrew early, the missing BMD assessments was estimated by the LOCF, provided the assessment was taken on or after at least one month on-therapy.
Measured: Baseline and Month 6
Percent Change From Baseline in BMD at the Trochanter at Month 6
BMD is the amount of bone mineral in bone tissue. BMD scan was done using DXA. It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calculated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value. ANCOVA model adjusted for treatment, center/region and Baseline BMD for the skeletal site under consideration as a continuous covariate for assessment. Region and treatment by region interaction was included in the model. Screening visit was considered as baseline for BMD. For participants who withdrew early, the missing BMD assessments was estimated by the LOCF, provided the assessment was taken on or after at least one month on-therapy.
Measured: Baseline and Month 6
Percent Change From Baseline in BMD at the Total Hip at Month 12
BMD is the amount of bone mineral in bone tissue. BMD scan was done using DXA. It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calculated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value. ANCOVA model adjusted for treatment, center/region and Baseline BMD for the skeletal site under consideration as a continuous covariate for assessment. Region and treatment by region interaction was included in the model. Screening visit was considered as baseline for BMD. For participants who withdrew early, the missing BMD assessments was estimated by the LOCF, provided the assessment was taken on or after at least one month on-therapy.
Measured: Baseline and Month 12
Percent Change From Baseline in BMD at the Femoral Neck at Month 12
BMD is the amount of bone mineral in bone tissue. BMD scan was done using DXA. It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calculated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value. ANCOVA model adjusted for treatment, center/region and Baseline BMD for the skeletal site under consideration as a continuous covariate for assessment. Region and treatment by region interaction was included in the model. Screening visit was considered as baseline for BMD. For participants who withdrew early, the missing BMD assessments was estimated by the LOCF, provided the assessment was taken on or after at least one month on-therapy.
Measured: Baseline and Month 12
Percent Change From Baseline in BMD at the Trochanter at Month 12
BMD is the amount of bone mineral in bone tissue. BMD scan was done using DXA. It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calculated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value. ANCOVA model adjusted for treatment, center/region and Baseline BMD for the skeletal site under consideration as a continuous covariate for assessment. Region and treatment by region interaction was included in the model. Screening visit was considered as baseline for BMD. For participants who withdrew early, the missing BMD assessments was estimated by the LOCF, provided the assessment was taken on or after at least one month on-therapy.
Measured: Baseline and Month 12
Percent Change in Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) From Baseline to Month 6 and Month 12
s-CTX is biomarker of bone resorption and formation. s-CTX was assessed during Screening, Month 6 and Month 12 in the Double-blind Treatment Phase. The value during Screening was considered as the Baseline value. Percent change from Baseline was assessed as the value at the indicated visit minus the Baseline value divided by the Baseline value x 100. A two-sided Wilcoxon rank sum test was used to compare percent change in s-CTX. Between group inferences is presented by p-values, Hodges-Lehmann estimates along with 95% confidence intervals.
Measured: Baseline, Month 6 and Month 12
Percent Change in Serum Procollagen Type I N Propeptideserum (s-PINP) From Baseline to Month 6 and Month 12
s-PINP is biomarker of bone resorption and formation. s-PINP was assessed during Screening, Month 6 and Month 12 in the Double-blind Treatment Phase. The value during Screening was considered as the Baseline value. Percent change from Baseline was assessed as the value at the indicated visit minus the Baseline value divided by the Baseline value x 100. A two-sided Wilcoxon rank sum test was used to compare percent change in serum CTX. Between group inferences is presented by p-values, Hodges-Lehmann estimates along with 95% confidence intervals.
Measured: Baseline, Month 6, Month 12
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 1, Month 3, Month 6, and Month 12
Baseline value was obtained at Randomization (Visit 3). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Change from Baseline in SBP and DBP was assessed at Baseline, Month 1, Month 3, Month 6, and Month 12.
Measured: Baseline, Month 1, Month 3, Month 6 and Month 12
Change From Baseline in Heart Rate at Month 1, Month 3, Month 6, and Month 12
Baseline value was obtained at Randomization (Visit 3). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Change from Baseline in heart rate was assessed at Baseline, Month 1, Month 3, Month 6 and Month 12.
Measured: Baseline, Month 1, Month 3, Month 6 and Month 12
Change From Baseline in Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Month 1, Month 6 and Month 12
Baseline values were obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Alanine amino transferase, alkaline phosphatase, aspartate amino transferase, and gamma glutamyl transferase were assessed at Baseline, Month 1, Month 6 and Month 12.
Measured: Baseline, Month 1, Month 6, and Month 12
Change From Baseline in Creatine Kinase, Lactate Dehydrogenase at Month 6 and Month 12.
Baseline values was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Creatine kinase and lactate dehydrogenase were assessed at Baseline, Month 6 and Month 12.
Measured: Baseline, Month 6 and Month 12
Change From Baseline in Albumin at Month 1, Month 6 and Month 12.
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Albumin was assessed at Baseline, Month 1, Month 6 and Month 12.
Measured: Baseline, Month 1, Month 6 and Month 12.
Change From Baseline in Globulin at Month 6 and Month 12.
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at indicated visit minus the Baseline value. Blood samples were collected for measurement. Globulin was assessed at Baseline, Month 6 and Month 12.
Measured: Baseline, Month 6 and Month 12
Change From Baseline in Hemoglobin and Total Protein at Month 6 and Month 12.
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at indicated visit minus the Baseline value. Blood samples were collected for measurement. Hemoglobin and total protein were assessed at Baseline, Month 6 and Month 12.
Measured: Baseline, Month 6 and Month 12
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils-total Absolute Neutrophil Count (ANC), White Blood Cell Count at Month 6 and Month 12.
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Basophils, eosinophils, lymphocytes, monocytes, platelet count, total neutrophils-total ANC and white blood cell count were assessed at Baseline, Month 6 and Month 12.
Measured: Baseline, Month 6 and Month 12
Change From Baseline in Calcium (Corrected), Calcium at Month 1, Month 6 and Month 12.
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Calcium (corrected) and calcium were assessed at Baseline, Month 1, Month 6 and Month 12.
Measured: Baseline, Month 1, Month 6 and Month 12.
Change From Baseline in Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorous, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen (BUN) at Month 6 and Month 12.
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Chloride, cholesterol, glucose, magnesium, inorganic phosphorous, potassium, sodium, triglycerides and urea/BUN were assessed at Baseline, Month 6 and Month 12.
Measured: Baseline, Month 6 and Month 12
Change From Baseline in Direct Bilirubin, Total Bilirubin at Month 1, Month 6 and Month 12.
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Direct bilirubin and total bilirubin were assessed at Baseline, Month 1, Month 6 and Month 12.
Measured: Baseline, Month 1, Month 6 and Month 12
Change From Baseline in Creatinine and Uric Acid at Month 6 and Month 12
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Creatinine and uric acid were assessed at Baseline, Month 6 and Month 12.
Measured: Baseline, Month 6 and Month 12
Change From Baseline in Hematocrit at Month 6 and Month 12.
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Hematocrit was assessed at Baseline, Month 6 and Month 12.
Measured: Baseline, Month 6 and Month 12.
Change From Baseline in Mean Corpuscle Hemoglobin at Month 6 and Month 12.
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Mean corpuscle hemoglobin was assessed at Baseline, Month 6 and Month 12.
Measured: Baseline, Month 6 and Month 12.
Change From Baseline in Mean Corpuscle Volume at Month 6 and Month 12.
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Mean corpuscle volume was assessed at Baseline, Month 6 and Month 12.
Measured: Baseline, Month 6 and Month 12
Change From Baseline in Red Blood Cell Count at Month 6 and Month 12
Baseline value was obtained at screening (visit 2). If missing, the most recent non-missing value was used. Change in baseline value was assessed as: Value at Indicated visit minus Baseline value. Blood samples were collected for measurement. Red blood cell count was assessed at Baseline, Month 6 and Month 12.
Measured: Baseline, Month 6 and Month 12
Number of Participants With Confirmed Anti-denosumab Antibody Formation at Baseline and Month 12
Anti-denosumab antibody formation was assessed at Baseline (Visit 3) and Month 12. Binding antibody and neutralizing antibody assays were used to assess number of participants with anti-denosumab antibody.
Measured: Baseline and Month 12
Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (Non-fatal Serious Adverse Events and Fatal Serious Adverse Events)
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. A serious adverse event (SAE) is 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, or is a congenital anomaly/birth defect or other events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the outcome listed above, liver injury and impaired liver function and grade 4 laboratory abnormalities. Number of participants with any AEs, serious non-fatal AEs, serious fatal AEs have been presented.
Measured: From start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2013 (estimated)
- Study startJan 2014
- Primary completionAug 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Osteoporosis, PostmenopausalStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 486 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02014467
- Sponsor's protocol ID
- 114165
- Status last verified
- Sep 2016
- First submitted
- 12 Dec 2013
- Last updated
- 31 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Twelve-Month Randomized, Double-Blind, Placebo Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy and Safety of Denosumab in Chinese Postmenopausal Women With Osteoporosis at Increased Risk of Fracture
- ClinicalTrials.gov ID
- NCT02014467
- Acronym / sponsor ID
- 114165
- Conditions
- Osteoporosis, Postmenopausal
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 486 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Jan 2014
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 18 Dec 2013 (estimated)
- Results
- Posted 31 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is to evaluate the efficacy and safety of denosumab 60 milligrams (mg) for 12 month treatment in Chinese postmenopausal women with osteoporosis at increased risk of fracture.
Detailed description
The aim of this Phase III, randomized, double-blind, placebo-controlled, parallel-group study is to evaluate the efficacy and safety of denosumab (DMAb) in Chinese postmenopausal women with osteoporosis at increased risk of fracture. The study design consists of two phases: Screening and 12-month Double-Blind treatment phase. Following the Screening phase, all eligible subjects will be randomized to receive Double-Blind DMAb (60 mg) or Placebo study medication in a 3:1 ratio. DMAb 60 mg and placebo will be administered as a single subcutaneous (SC) injection at the beginning of the Double-Blind phase and at 6 months following the initial dose. All subjects will receive daily supplementation of oral elemental calcium (at least 600 mg) and vitamin D (at least 400 International Units [IU]). The primary objective is to determine the effects of DMAb compared to placebo with respect to mean percent change in BMD at the lumbar spine, as measured by dual-energy x-ray absorptiometry (DXA), from Baseline to Month 12. Secondary objectives include the evaluation between the DMAb and placebo treatment groups: change in BMD: at the lumbar spine (Month 6), total hip (Months 6 and 12), femoral neck (Months 6 and 12) and trochanter (Months 6 and 12); and serum biomarkers of bone formation and resorption (Months 6 and 12). Clinical safety of denosumab will also be assessed in this population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Denosumab 60mg | Experimental | Drug: Denosumab, Dietary Supplement: Elemental Calcium, Dietary Supplement: Vitamin Dinjection |
| Placebo | Placebo comparator | Drug: Placebo, Dietary Supplement: Elemental Calcium, Dietary Supplement: Vitamin Dinjection |
Who may qualify
- Ages
- 60 to 90 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subject is willing and able to provide written informed consent.
- Of Chinese origin - defined as being born in China, having four ethnic Chinese grandparents.
- Ambulatory woman between the age of 60 and 90 years, inclusive.
- The subject has a BMD absolute value consistent with a T-score<-2.5 and >-4.0 at either the lumbar spine or total hip.
- All subjects must have at least one of following additional the risk factors:
Key exclusion criteria (42 listed)
- Bone/metabolic disease:
- Any metabolic bone disease, e.g., osteomalacia or osteogenesis imperfecta, which may interfere with the interpretation of the findings.
- Paget's disease Cushing's disease Hyperprolactinemia
- Current hyperparathyroidism or hypoparathyroidism by medical record
- Thyroid condition: Hyperthyroidism or hypothyroidism. Only subjects with hypothyroidism who are on stable thyroid hormone replacement therapy may be allowed per the following criteria:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DenosumabInjection | Drug | Denosumab 60mg |
| PlaceboInjection | Drug | Placebo |
| Elemental CalciumOral, at least 600 mg | Dietary supplement | Denosumab 60mg, Placebo |
| Vitamin DOral, at least 400 IU | Dietary supplement | Denosumab 60mg, Placebo |
Primary outcome
Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine at Month 12
Time frame: Baseline and Month 12
Bone mineral density (BMD) is the amount of bone mineral in bone tissue. BMD scan was done using dual energy x-ray absorptiometry (DXA). It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calcuated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value. The analysis was performed by Analysis of Covariance (ANCOVA) model adjusted for treatment, region and Baseline BMD for the skeletal site under consideration as a continuous covariate for assessment. Region and treatment by region interaction was included in the model. Screening visit was considered as Baseline for BMD. For participants who withdrew early, the missing BMD assessments was estimated by the Last Observation Carried Forward (LOCF), provided the assessment was taken on or after at least one month on-therapy.
27 secondary outcomes
Percent Change From Baseline in BMD at the Lumbar Spine at Month 6
Time frame: Baseline and Month 6
Percent Change From Baseline in BMD at the Total Hip at Month 6
Time frame: Baseline and Month 6
Percent Change From Baseline in BMD at the Femoral Neck at Month 6
Time frame: Baseline and Month 6
Percent Change From Baseline in BMD at the Trochanter at Month 6
Time frame: Baseline and Month 6
Percent Change From Baseline in BMD at the Total Hip at Month 12
Time frame: Baseline and Month 12
Percent Change From Baseline in BMD at the Femoral Neck at Month 12
Time frame: Baseline and Month 12
Percent Change From Baseline in BMD at the Trochanter at Month 12
Time frame: Baseline and Month 12
Percent Change in Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) From Baseline to Month 6 and Month 12
Time frame: Baseline, Month 6 and Month 12
Percent Change in Serum Procollagen Type I N Propeptideserum (s-PINP) From Baseline to Month 6 and Month 12
Time frame: Baseline, Month 6, Month 12
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 1, Month 3, Month 6, and Month 12
Time frame: Baseline, Month 1, Month 3, Month 6 and Month 12
Change From Baseline in Heart Rate at Month 1, Month 3, Month 6, and Month 12
Time frame: Baseline, Month 1, Month 3, Month 6 and Month 12
Change From Baseline in Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Month 1, Month 6 and Month 12
Time frame: Baseline, Month 1, Month 6, and Month 12
Change From Baseline in Creatine Kinase, Lactate Dehydrogenase at Month 6 and Month 12.
Time frame: Baseline, Month 6 and Month 12
Change From Baseline in Albumin at Month 1, Month 6 and Month 12.
Time frame: Baseline, Month 1, Month 6 and Month 12.
Change From Baseline in Globulin at Month 6 and Month 12.
Time frame: Baseline, Month 6 and Month 12
Change From Baseline in Hemoglobin and Total Protein at Month 6 and Month 12.
Time frame: Baseline, Month 6 and Month 12
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils-total Absolute Neutrophil Count (ANC), White Blood Cell Count at Month 6 and Month 12.
Time frame: Baseline, Month 6 and Month 12
Change From Baseline in Calcium (Corrected), Calcium at Month 1, Month 6 and Month 12.
Time frame: Baseline, Month 1, Month 6 and Month 12.
Change From Baseline in Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorous, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen (BUN) at Month 6 and Month 12.
Time frame: Baseline, Month 6 and Month 12
Change From Baseline in Direct Bilirubin, Total Bilirubin at Month 1, Month 6 and Month 12.
Time frame: Baseline, Month 1, Month 6 and Month 12
Change From Baseline in Creatinine and Uric Acid at Month 6 and Month 12
Time frame: Baseline, Month 6 and Month 12
Change From Baseline in Hematocrit at Month 6 and Month 12.
Time frame: Baseline, Month 6 and Month 12.
Change From Baseline in Mean Corpuscle Hemoglobin at Month 6 and Month 12.
Time frame: Baseline, Month 6 and Month 12.
Change From Baseline in Mean Corpuscle Volume at Month 6 and Month 12.
Time frame: Baseline, Month 6 and Month 12
Change From Baseline in Red Blood Cell Count at Month 6 and Month 12
Time frame: Baseline, Month 6 and Month 12
Number of Participants With Confirmed Anti-denosumab Antibody Formation at Baseline and Month 12
Time frame: Baseline and Month 12
Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (Non-fatal Serious Adverse Events and Fatal Serious Adverse Events)
Time frame: From start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Denosumab, Elemental Calcium and Vitamin D in people with Osteoporosis, Postmenopausal, run by GlaxoSmithKline at 8 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine at Month 12 (time frame: Baseline and Month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2016.