osteoporosis in patients with multiple sclerosis MedDRA version: 14.1 Level: PT Classification code 10049088 Term: Osteopenia System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders MedDRA version: 14.1 Level: PT Classification code 10031282 Term: Osteoporosis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Trade Name: Aclasta 5 mg Infusionslösung
Product Name: Aclasta
Product Code: ZOL446H
Pharmaceutical Form: Solution for infusion
CAS Number: 165800-06-6
Other descriptive name: ZOLEDRONIC ACID MONOHYDR
Sponsors
Novartis Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Written informed consent to participate in the trial 2) Males and Females between 18 and 75 years of age 3) Definite diagnosis of multiple sclerosis as defined by 2005 revised McDonald criteria (Appendix 3) 4) MS-subtype: RRMS, SPMS, PPMS 5) EDSS score between 2.5 to 6.5 (including) 6) No immunomodulatory treatment for MS within the last 30 days or stable and well tolerated therapy with any beta-interferon formulation, glatirameracetate or fingolimod for at least 30 days immediately prior to baseline. 7) BMD T-score of less or equal to -2.0 but not less or equal to -4.0 at the lumbar spine (L1-L4 with at least 2 evaluable vertebrae) and/or total hip region and/or femoral neck in recent DXA-scan (= 3 months). The DXA-scans for all assessments need to be performed with the same DXA-machine. 8) Previous participation in CZOL446HDE39 9) 25-OH vitamin D level greater or equal to 15 ng/ml 10) Sufficient ability to read, write and communicate comprehensibly and comply to study procedures 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: 1) Contraindications against Calcium and Vitamin D according to the summary product characteristics 2) Contraindications against zoledronic acid according to the summary of product characteristics 3) Hypersensitivity to bisphosphonates, Calcium and Vitamin D or to drugs with similar chemical structures 4) More than one osteoporotic fracture 5) Severe disability or any clinical impairment that can prevent the patient to meet all study requirements 6) Concomitant medication with influence on bone mineral density (eg. enzyme-inducing antiepileptics like Carbamazepin, Phenytoin, Phenobarbital, Primidon) 7) Any neurological disorder other than MS which is known to affect bone mineral density (e.g. muscular dystrophy, severe paresis due to other reasons than MS, degenerative nervous disorder, stroke) 8) Any bone disorder other than osteoporosis known to affect bone mineral density (e.g. paget´s disease, osteogenesis imperfecta, multiple myeloma) 9) Study personnel or first degree relatives of investigator(s) must not be included in the study. 10) Women who are - pregnant or breast feeding (pregnancy defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mlU/ml)). - menstruating and capable of becoming pregnant* and not practicing two medically approved methods of contraception (Pearl Index 40 mlU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy **examples of particularly reliable methods with Pearl Index (PI) < 1, according to guidelines of Deutsche Gesellschaft für Gynäkologie und Geburtshilfe: • Combination pill with estrogen and gestagen (no minipill, PI=0.1-0.9) • Vaginal ring (NuvaRing®, PI=0.65 uncorr.; 0.4 corr.) • Contraceptive patch (EVRA®, PI=0.72 uncorr.; 0.9 corr.) • Estrogen-free ovulation inhibitors (Cerazette®, PI=0.14) • Progestin-containing contraceptives (Implanon®, PI=0-0.08) • Injectable 3-month depot progestins (PI=0.3-1.4; 0.88 corr.) • Intra-uterine progestine device (Mirena®, PI=0.16) 11) Baseline renal insufficiency (calculated creatinine clearance less than 35.0 mL/min); Urine dipstick greater than or equal to 2+ protein at Visit 1 without evidence of contamination or bacteriuria (may be repeated one time at least a week apart if there is suspicion of contamination). 12) Pre-existing hypocalcemia = 2.0 mmol/L (8.0 mg/dL) not adequately treated by intake of calcium and vitamin D before baseline 13) Use of testosterone therapy within one year prior to randomization 14) Use of systemic corticosteroids (oral or i.v.) in the last year with more than 7.5 mg/day prednisolone (or equivalent) continuously for more than four weeks. NOTE: Use of corticosteroids in forms such as topical creams, nasal or inhaled formulations or those injected locally (eg. intra-articularly, ocular, intrsthecal) or pulsed therapy for MS-relapses are NOT exclusionary. 15) Prior exposure to anabolic steroids or growth hormone within 6 months prior to randomization 16) Treatment with any investigational drug(s) and/or devices within 30 days prior to randomization. 17) Treat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that zoledronic acid has superior efficacy compared with placebo on the percent change of bone mineral density (BMD) as assessed by the T-score at lumbar spine and total hip region at month 12 relative to screening as measured by Dual X-ray Absorptiometry (DXA) in MS patients suffering from osteoporosis.;Secondary Objective: To further explore efficacy of zoledronic acid the following secondary outcomes will be evaluated •change from baseline to month 6 of BMD at lumbar spine,total hip, and femoral neck as measured by DXA •change from baseline to month 12 of BMD at femoral neck as measured by DXA •change from baseline to end of study of BMD at lumbar spine, total hip, and femoral neck as measured by DXA •To evaluate the effect of zoledronic acid vs. placebo on the course of disease in MS- patients; the Expanded Disability Status Scale (EDSS) will be used at month 12 •To evaluate the effect of zoledronic acid vs. placebo on the number of new clinically evident fractures at month 12 and at the end of the additional 1 year open label phase •To evaluate safety and tolerability of zoledronic acid versus placebo in MS-patients •To evaluate safety and tolerability of zoledronic acid in MS patients at the end of the additional 1 year open label phase ;Primary end point(s): The co-primary endpoints are the change in bone mineral density as measured by the T-score from the DXA of lumbar spine and total hip total region (baseline to week 53). The DXA is a widely used measure of bone mineral density. | — |
Countries
Germany
Outcome results
None listed