Zoledronic Acid in MS-patients With Osteoporosis

Multiple Sclerosis Clinical Trial

— EXALT  

Official title:

A 1-year, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy of Zoledronic Acid 5 mg (Aclasta®) on Bone Mineral Density in Patients With Multiple Sclerosis Followed by a 1-year Open-label Treatment Phase

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01166178
• Other study ID #: CZOL446HDE40
• Secondary ID: 2009-011888-37
• Status: Terminated
• Phase: Phase 3
• First received: July 19, 2010
• Last updated: October 24, 2013
• Start date: October 2010
• Est. completion date: June 2012

Study information

• Verified date: October 2013
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 29
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion:

• 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

Exclusion criteria:

• 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

• 25-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

• Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Osteoporosis
• Sclerosis

Intervention

Drug:
• Zoledronic Acid
Zoledronic acid 5 mg once a year via intravenous infusion
• Placebo
Placebo to zoledronic acid once a year via intravenous infusion

Dietary Supplement:
• Calcium and Vitamin D combination
Calcium 500 mg and Vitamin D 400 IU combined tablet, taken orally twice a day

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Bamberg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Kassel
Germany	Novartis investigative site	Leipzig
Germany	Novartis Investigative Site	Leverkusen
Germany	Novartis investigative site	Ludwigshafen
Germany	Novartis investigative site	Magdeburg
Germany	Novartis investigative site	Muenchen
Germany	Novartis investigative site	Numbrecht
Germany	Novartis investigative site	Oldenburg
Germany	Novartis Investigative Site	Siegen
Germany	Novartis investigative site	Stade

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	Change in Bone Mineral Density of the Lumbar Spine at 6 Months	Change in bone mineral density (BMD) of the lumbar spine was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 6.; 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 6	No
Secondary	Change in Bone Mineral Density of the Femoral Neck at 6 Months	Change in bone mineral density (BMD) of the femoral neck was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 6.; 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 6	No
Secondary	Change in Bone Mineral Density of the Total Hip at 6 Months	Change in bone mineral density (BMD) of the total hip was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 6. 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 6	No
Secondary	Change in Bone Mineral Density of the Femoral Neck at 12 Months	Change in bone mineral density (BMD) of the femoral neck 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	No
Secondary	Change in Bone Mineral Density of the Lumbar Spine at 24 Months	Change in bone mineral density (BMD) of the lumbar spine was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 24.; 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 24	No
Secondary	Change in Bone Mineral Density of the Total Hip Region at 24 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 24.; 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 24	No
Secondary	Change in Bone Mineral Density of the Femoral Neck at 24 Months	Change in bone mineral density (BMD) of the femoral neck was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 24.; 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 24	No
Secondary	Course of Disease in Multiple Sclerosis Patients	The course of disease in Multiple Sclerosis (MS) patients was measured comparing results from the Expanded Disability Status Scale (EDSS) from screening and month 12. EDSS is a scale, ranging from 0 (normal) to 10 (death due to MS) for assessing neurologic impairment in MS. It is based on a weighting scheme of eight functional systems. The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel&Bladder, Cerebral and Other functions. EDSS was assessed by the treating neurologist.	Screening (day -21 to -1) and month 12	No
Secondary	Adverse Events and Serious Adverse Events Comparison of Treatment Groups	Adverse Events and Serious Adverse events are reported in the safety section.	24 months	Yes