Zoledronic Acid in MS-patients With Osteoporosis

NCT01166178 | Terminated Phase 3 Results

• 2 other identifiers: CZOL446HDE402009-011888-37
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 15

Brief Summary

This study is designed to evaluate the efficacy and safety of zoledronic acid 5 mg intravenous (i.v.) relative to placebo in Multiple Sclerosis (MS) patients with osteoporosis and to support the optimal use of zoledronic acid for this indication. Primary objective is the change of Bone Mineral Density (BMD) at lumbar spine (L1-L4) and total hip region assessed by T-Score at month 12 relative to screening as measured by Dual X-ray Absorptiometry (DXA). This double-blind period will be followed by a 52-week open-label treatment phase to assess long-term efficacy and safety of zoledronic acid in these patients.

Conditions

Osteoporosis; Multiple Sclerosis

Keywords

Multiple Sclerosis; Osteoporosis; Zoledronic Acid

Outcome Measures

Primary Outcomes (2)

• Change in Bone Mineral Density of the Lumbar Spine at 12 Months

  Change in bone mineral density (BMD) of the lumbar spine was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 12. A DXA scanner is a device that uses x-ray beams to measure the amount of minerals in the bone.

  Screening (day -21 to -1) and month 12

• Change in Bone Mineral Density of the Total Hip Region at 12 Months

  Change in bone mineral density (BMD) of the total hip region was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 12. A DXA scanner is a device that uses x-ray beams to measure the amount of minerals in the bone.

  Screening (day -21 to -1) and month 12

Secondary Outcomes (9)

• Change in Bone Mineral Density of the Lumbar Spine at 6 Months

  Screening (day -21 to -1) and month 6

• Change in Bone Mineral Density of the Femoral Neck at 6 Months

  Screening (day -21 to -1) and month 6

• Change in Bone Mineral Density of the Total Hip at 6 Months

  Screening (day -21 to -1) and month 6

• Change in Bone Mineral Density of the Femoral Neck at 12 Months

  Screening (day -21 to -1) and month 12

• Change in Bone Mineral Density of the Lumbar Spine at 24 Months

  Screening (day -21 to -1) and month 24

Study Arms (2)

Zoledronic Acid

EXPERIMENTAL

Participants received zoledronic acid infusion in addition to calcium and vitamin D

Drug: Zoledronic Acid; Dietary Supplement: Calcium and Vitamin D combination

Placebo

PLACEBO COMPARATOR

Participants received placebo to zoledronic acid infusion in addition to calcium and vitamin D

Drug: Placebo; Dietary Supplement: Calcium and Vitamin D combination

Interventions

Zoledronic Acid DRUG

Zoledronic acid 5 mg once a year via intravenous infusion

Zoledronic Acid

Placebo DRUG

Placebo to zoledronic acid once a year via intravenous infusion

Placebo

Calcium and Vitamin D combination DIETARY_SUPPLEMENT

Calcium 500 mg and Vitamin D 400 IU combined tablet, taken orally twice a day

Placebo; Zoledronic Acid

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent to participate in the trial
• Definite diagnosis of Multiple Sclerosis (MS) as defined by 2005 revised McDonald criteria
• MS-subtype: Relapsing-remitting MS (RRMS), Secondary progressive MS (SPMS), Primary progressive MS (PPMS)
• Expanded Disability Status Scale (Kurtzke's scale; EDSS) score between 2.5 to 6.5 (including both)
• Bone mineral density (BMD) T-score of less or equal to -2.0 and more 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 Dual X-Ray Absorptiometry (DXA)-scan (\< or = 3 months)
• Sufficient ability to read, write and communicate comprehensibly and comply to study procedures
• No immunomodulatory treatment for MS within the last 30 days or stable and well tolerated therapy with any beta-interferon formulation, or glatirameracetate or fingolimod for at least 30 days immediately prior to baseline

You may not qualify if:

• Contraindications against Calcium and Vitamin D and zoledronic acid according to the summary product characteristics
• More than one osteoporotic fracture
• Concomitant medication with influence on bone mineral density (eg. enzyme- inducing antiepileptics like Carbamazepin, Phenytoin, Phenobarbital, Primidon)
• Any neurological disorder other than MS which is known to affect bone mineral density (e.g. muscular dystrophy, severe paresis for other reasons than MS, degenerative nervous disorder, stroke)
• Women who are pregnant or breast feeding, or menstruating and capable of becoming pregnant.
• Baseline renal insufficiency
• OH vitamin D level \< 10 ng/ml at screening
• Serum calcium levels \> 2.75 mmol/l (11.0 mg/dL) or \< 2.00 mmol/L (8.0 mg/dL) at screening

Sponsors & Collaborators

• Novartis: lead

Study Sites (15)

Novartis Investigative Site

Bamberg, Germany

Location

Novartis Investigative Site

Berlin, Germany

Location

Novartis Investigative Site

Bochum, Germany

Location

Novartis Investigative Site

Hamburg, Germany

Location

Novartis Investigative Site

Heidelberg, Germany

Location

Novartis Investigative Site

Kassel, Germany

Location

Novartis investigative site

Leipzig, Germany

Location

Novartis Investigative Site

Leverkusen, Germany

Location

Novartis investigative site

Ludwigshafen, Germany

Location

Novartis investigative site

Magdeburg, Germany

Location

Novartis investigative site

München, Germany

Location

Novartis investigative site

Nümbrecht, Germany

Location

Novartis investigative site

Oldenburg, Germany

Location

Novartis Investigative Site

Siegen, Germany

Location

Novartis investigative site

Stade, Germany

Location

MeSH Terms

Conditions

Osteoporosis; Multiple Sclerosis

Interventions

Zoledronic Acid; Calcium

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals; Blood Coagulation Factors; Biological Factors

Limitations and Caveats

Study termination due to small number of participants recruited lead to lack of power for analysis of all outcome measures.

Results Point of Contact

• Title: Study Director
• Organization: Novartis

41 61 324 1111

Study Officials

• Novartis Pharmceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2010
• First Posted: July 20, 2010
• Study Start: October 1, 2010
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: November 26, 2013
• Results First Posted: November 26, 2013

Record last verified: 2013-10

Locations

DE (15)