Treatment of osteoporosis in men MedDRA version: 8.1 Level: LLT Classification code 10031282 Term: Osteoporosis
Conditions
Interventions
Trade Name: Aclasta 5 mg solution for infusion
Product Name: NA
Product Code: NA
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ZOLEDRONIC ACID
CAS Number: 118072938
Current Sponsor c
Sponsors
Novartis Pharma Services AG
Novartis CPO to fill
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: • Male patients between 50 and 85 years of age, inclusive • At least three readable L1-L4 vertebra, confirmed by the centralized expert readers prior to randomization • Bone mineral density T-score of less than or equal to -2.5 SD at the total hip or femoral neck AND less than or equal to -1.5 SD at the lumbar spine as confirmed by the central expert reader. OR • Bone mineral density T-score of less than or equal to -1.5 SD at the total hip or femoral neck as confirmed by the central expert reader, AND at least 1 up to a maximum of 3 prevalent vertebral fractures of mild or moderate grade as defined by the modified Genant method for males and confirmed by the central expert reader. Important: The BMD T-score must be confirmed by the central expert reader prior to randomization. Additionally, vertebral x-rays (lateral thoracic and lumbar views) will be performed and must be submitted to the central imaging laboratory for confirmation of prevalent vertebral fractures prior to randomization. Please note: Patients with more than 3 or any severe vertebral fracture or patients with acute painful osteoporotic fractures requiring treatment with any of the prohibited medications can not be included in the trial. 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Patients with 25-(OH) Vitamin D levels less than 15 ng/mL at Visit 1. If the vitamin D level is < 15 ng/ml the patient should receive a loading dose of 75,000-100,000 IU of vitamin D IM or orally once at visit 1 and have the vitamin D test repeated at visit 1A. This repeat test for vitamin D should be done after at least 3 weeks have passed since the loading dose was given. • Baseline renal insufficiency (calculated creatinine clearance less than 30.0 mL/min) at Visit 1 and/or Visit 1A or urine dipstick greater than or equal to 2+ protein without evidence of contamination or bacteriuria (may be repeated one time at least a week apart if there is suspicion of contamination). Patients with calculated creatinine clearance equal to or greater than 30.0 mL/min and less than 60.0 mL/min or serum creatinine greater than the upper limit of normal at Visit 1 must be confirmed at a second visit (Visit 1A). Patients with calculated creatinine clearance greater than 60.0 mL/min and serum creatinine within normal limits at Visit 1 do not require re-test. • Patients who require re-test of creatinine clearance at Visit 1A will be excluded if there is an increase in serum creatinine greater than 0.5 mg/dL between Visit 1 and Visit 1A. Serum creatinine may be repeated once and the investigator may discuss with the Novartis Clinical Research Physician whether to consider the patient’s entry into the trial based on the repeated serum creatinine result and the patient’s overall renal status. • Hypercalcemia, defined as serum calcium greater than or equal to 2.75 mmol/L (11.0 mg/dL) at Visit 1 or Visit 1A. • Hypocalcemia, defined as serum calcium less than or equal to 2.0 mmol/L (8.0 mg/dL) at Visit 1 or Visit 1A. • AST or ALT greater than 3 times the upper limit of normal • Serum alkaline phosphatase greater than 1.5 times the upper limit of normal • Previous use of calcitonin except according to the following washout schedule, measured from randomization: - 6 months (if used for 12 weeks or longer) - 3 months (if used for greater than or equal to 4 weeks but less or equal to 12 weeks) • Hypersensitivity to bisphosphonates • Prior treatment with i.v. bisphosphonates within the last 2 years prior to randomization • Use of oral bisphosphonates except according to the following washout schedule, measured from the date of randomization: - 2 years (if used for 48 weeks or longer) - 1 year (if used for greater than 8 weeks but less than 48 weeks) - 6 months (if used for greater than 2 weeks but less than or equal to 8 weeks) • Any prior use of PTH for more than 1 week; if used for less than or equal to 1 week, the washout period for PTH is 3 months prior to randomization. • Any prior use of strontium ranelate or sodium fluoride • Use of testosterone therapy within one year prior to randomization. • Chronic use of systemic corticosteroids (oral or i.v.) within the last year: NOTE: Use of corticosteroids in forms such as topical creams, nasal or inhaled formulations or those injected locally (intra-articularly) are NOT exclusionary. • Prior exposure to anabolic steroids or growth hormone within 6 months prior to randomization • Treatment with any investigational drug(s) and/or devices within 30 days prior to randomization. • History of iritis or uveitis, except when secondary to trauma, and must have resolved for more
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to demonstrate the superiority of treatment with zoledronic acid relative to placebo in reducing the incidence of vertebral fractures in men with osteoporosis. The incidence of new morphometric vertebral fractures will be evaluated based on the proportion of new morphometric vertebral fractures over 24 months.;Secondary Objective: The secondary objectives include the evaluation of the following parameters: • Time to first clinical vertebral fracture • Proportion of patients with at least one new vertebral fracture over 12 months. • Proportion of patients with at least one new moderate or severe morphometric vertebral fracture over 12 and 24 months • The change in height at Month 12 and Month 24. • The percent change of BMD at lumbar spine and total hip at Month 6, Month 12 and Month 24 relative to baseline as measured by DXA in a sub-set of at least 100 evaluable patients at selected sites. • The changes in biochemical markers of bone resorption and bone formation at all post-baseline time points relative to baseline in a sub-set of at least 100 evaluable patients at selected sites. • Time to first clinical fracture • Time to first non-vertebral fracture • The overall safety of zoledronic acid compared to placebo in osteoporotic men. ;Primary end point(s): The primary efficacy endpoint is the proportion of patients with at least one new morphometric vertebral fracture over 24 months. | — |
Countries
Austria, Belgium, Czech Republic, Finland, Germany, Hungary, Iceland, Italy, Poland, Portugal, Sweden, United Kingdom
Outcome results
None listed