Study to Evaluate the Safety and Efficacy of Denosumab and Actonel® in Post Menopausal Women Transitioned From Alendronate Therapy

Conditions: Postmenopausal osteoporosis
MedDRA version: 14.0Level: PTClassification code 10031285Term: Osteoporosis postmenopausalSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Registration Number: EUCTR2009-010587-42-DE

Lead Sponsor: Amgen Inc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 800

Inclusion Criteria

Subjects will meet the following inclusion criteria prior to enrolment:
- Ambulatory, postmenopausal women (based on medical history) aged 55 years or older at screening:
• Postmenopause will be defined as no vaginal bleeding or spotting for at least 12 months
• If the subject is < 60 years old and there is uncertainty regarding menopausal status, confirmation of serum FSH (= 50 mIU/mL) and serum estradiol (= 20 pg/mL) must be obtained
- Have received their first prescription of daily or weekly alendronate therapy, for the treatment for postmenopausal osteoporosis at least 1 month prior to screening. Use of raloxifene, calcitonin prior to alendronate treatment will be allowed. Prior and current use of vitamin D and calcium will be allowed.
• Hormone replacement therapy (e.g. estrogen use for mitigation of
menopausal symptoms) will be allowed.
- Subject has demonstrated 1 of the following:
• Has stopped oral alendronate therapy (is denoted as non-persistent) before the screening visit.
• Is still taking oral alendronate therapy but demonstrates low adherence to therapy assessed by a score of less than 6 on the Osteoporosis Specific Morisky Medication Adherence Scale (OS-MMAS)
- Provide signed informed consent before any study-specific procedures are conducted
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 284
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 586

Exclusion Criteria

Subjects meeting any of the following criteria are not eligible for participation in the study:
- Any prior or current use of medications prescribed for osteoporosis treatment other than:
• oral daily or weekly alendronate
• Hormone replacement therapy (e.g. estrogen use to mitigate
menopausal symptoms)
• calcium and vitamin D
• prior use of raloxifene and calcitonin before alendronate therapy was initiated will
be allowed. Use of these therapies must have stopped prior to initiating oral
alendronate and their current use is not allowed
- Hypersensitivity to Actonel® or other constituents of Actonel® tablets
- Contraindicated or poorly tolerant of alendronate therapy; contraindications for alendronate therapy include:
• Abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia
• Inability to stand or sit upright for at least 30 minutes
- Active gastric or duodenal ulcer; history of significant gastrointestinal bleed requiring hospitalization or transfusion, or dyspepsia or gastro esophageal reflux disease that is uncontrolled by medication
- Known sensitivity to mammalian cell derived drug products
- Known intolerance to calcium supplements
- Malignancy within the last 5 years (except cervical carcinoma in situ or basal cell carcinoma
- Vitamin D deficiency [25(OH) vitamin D level < 20 ng/mL (< 49.9 nmol/L)] - Repletion will be allowed and subjects may be re-screened
- Current hypo- or hypercalcemia based on the central laboratory reference ranges
- Uncontrolled hyper- or hypothyroidism (stable on antithyroid therapy or post-ablation is allowed, if the central laboratory TSH is within the normal range)
- Hyper- or hypoparathyroidism per the central laboratory reference ranges
- Any metabolic bone disease, eg, osteomalacia or osteogenesis imperfecta, Paget’s
disease of bone, that may interfere with the interpretation of the findings, and other
disorders including
• Significantly impaired renal function as determined by a derived glomerular
filtration rate (GFR) (using the Modification of Diet in Renal Disease [MDRD]
formula) of = 30 mL/min/1.73 m2 calculated by the central laboratory.
• Clinically determined malabsorption syndrome that may result from disorders such as celiac disease, gastric bypass surgery, bowel
resection, uncontrolled diarrhea and steatorrhea.
• Elevated transaminases = 2.0 x upper limits of normal (ULN)
- Height, weight or girth which may preclude accurate DXA measurements
- Fewer than 2 lumbar vertebrae (L1-L4) able to be evaluated by DXA
- Known to have tested positive for human immunodeficiency virus
- Previous participation in clinical trials with denosumab within the last 12 months (regardless of treatment)
- Any laboratory abnormality, physical or psychiatric disorder (including substance abuse in last 12 months) which, in the opinion of the investigator, will prevent the subject from giving written informed consent or completing the study or interfere with the interpretation of the study results
- Currently enrolled in or within 30 days of ending another investigational device or drug trial(s)
- Administration of any of the following treatments within 3 months of screening
• Tibolone
• Anabolic steroids or testosterone
• Glucocorticosteroids (= 5 mg prednisone equivalent per day for more than 10
days or a total cumulative dose of = 50 mg)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the study is to evaluate the effect of denosumab 60 mg every 6 months (Q6M) compared with Actonel® 150mg monthly (QM) on total hip Bone Mineral Density (BMD) at 12 months in postmenopausal women transitioning from previous alendronate therapy.;Secondary Objective: To evaluate the effects of denosumab 60 mg Q6M and Actonel® 150 mg QM on:<br>• CTX (in a subset of subjects) at 1 month<br>• BMD at the femoral neck at 12 months<br>• BMD at the lumbar spine at 12 months;Primary end point(s): Percent change from baseline in BMD at the total hip ;Timepoint(s) of evaluation of this end point: 12 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Percent change from baseline in CTX (in subset of subjects) <br>• Percent change from baseline in BMD at the femoral neck <br>• Percent change from baseline in BMD at the lumbar spine;Timepoint(s) of evaluation of this end point: Percent change from baseline in CTX (in subset of subjects) at 1 month<br>• Percent change from baseline in BMD at the femoral neck at 12 months<br>• Percent change from baseline in BMD at the lumbar spine at 12 months

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