OsteoporosisPhase 3EXALTNCT01166178

Zoledronic Acid in MS-patients With Osteoporosis

A Phase 3 study testing Zoledronic Acid and Calcium and Vitamin D combination in people with Osteoporosis and Multiple Sclerosis, run by Novartis at 15 sites in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Osteoporosis, Multiple Sclerosis
What is being tested?: Zoledronic Acid and Calcium and Vitamin D combination
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 29 participants
Where: 15 sitesGermany
Study dates: Oct 2010to Jun 2012
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

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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

Trial locations and contacts

15 sites in 1 country.

City, postcode or hospital

15 sites in 1 country

Germany15 sites

Novartis Investigative Site
Bamberg
Novartis Investigative Site
Berlin
Novartis Investigative Site
Bochum
Novartis Investigative Site
Hamburg
Novartis Investigative Site
Heidelberg
Novartis Investigative Site
Kassel
Novartis investigative site
Leipzig
Novartis Investigative Site
Leverkusen
Novartis investigative site
Ludwigshafen
Novartis investigative site
Magdeburg
Novartis investigative site
München
Novartis investigative site
Nümbrecht
Novartis investigative site
Oldenburg
Novartis Investigative Site
Siegen
Novartis investigative site
Stade

Other trials in Germany

About this study

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

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
Being tested: Zoledronic Acid, Placebo, Calcium and Vitamin D combination
Keywords: Multiple Sclerosis, Osteoporosis, Zoledronic Acid
Medical subject headings: Osteoporosis, Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Zoledronic AcidDrug
Zoledronic acid 5 mg once a year via intravenous infusion
PlaceboDrug
Placebo to zoledronic acid once a year via intravenous infusion
Calcium and Vitamin D combinationDietary supplement
Calcium 500 mg and Vitamin D 400 IU combined tablet, taken orally twice a day

Study groups in NCT01166178
Study group	Role	What they receive
Zoledronic Acid	Experimental	Participants received zoledronic acid infusion in addition to calcium and vitamin D Receives: 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 Receives: Drug: Placebo; Dietary Supplement: Calcium and Vitamin D combination

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: Screening (day -21 to -1) and month 12

Secondary outcomes (9)

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.
Measured: Screening (day -21 to -1) and month 6
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.
Measured: Screening (day -21 to -1) and month 6
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.
Measured: Screening (day -21 to -1) and month 6
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.
Measured: Screening (day -21 to -1) and month 12
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.
Measured: Screening (day -21 to -1) and month 24
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.
Measured: Screening (day -21 to -1) and month 24
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.
Measured: Screening (day -21 to -1) and month 24
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.
Measured: Screening (day -21 to -1) and month 12
Adverse Events and Serious Adverse Events Comparison of Treatment Groups
Adverse Events and Serious Adverse events are reported in the safety section.
Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2010Jun 2012

First posted20 Jul 2010 (estimated)
Study startOct 2010
Primary completionJun 2012
Study completionJun 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for OsteoporosisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 29 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01166178
Sponsor's protocol ID: CZOL446HDE40
Other IDs: 2009-011888-37, 2009
Acronym: EXALT
Status last verified: Oct 2013
First submitted: 19 Jul 2010
Last updated: 26 Nov 2013
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Osteoporosis trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01166178
Acronym / sponsor ID: EXALT / CZOL446HDE40
Conditions: Osteoporosis, Multiple Sclerosis
Keywords: Multiple Sclerosis, Osteoporosis, Zoledronic Acid
Phase: Phase 3
Study type: Interventional
Recruitment status: Terminated
Enrolment: 29 participants (actual)
Lead sponsor: NovartisIndustry (pharma, biotech, devices)
Study start: Oct 2010
Primary completion: Jun 2012 (actual)
Study completion: Jun 2012 (actual)
First posted: 20 Jul 2010 (estimated)
Results: Posted 26 Nov 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Zoledronic Acid	Experimental	Drug: Zoledronic Acid, Dietary Supplement: Calcium and Vitamin D combinationParticipants received zoledronic acid infusion in addition to calcium and vitamin D
Placebo	Placebo comparator	Drug: Placebo, Dietary Supplement: Calcium and Vitamin D combinationParticipants received placebo to zoledronic acid infusion in addition to calcium and vitamin D

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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)

Key exclusion criteria (9 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Zoledronic AcidZoledronic acid 5 mg once a year via intravenous infusion	Drug	Zoledronic Acid
PlaceboPlacebo to zoledronic acid once a year via intravenous infusion	Drug	Placebo
Calcium and Vitamin D combinationCalcium 500 mg and Vitamin D 400 IU combined tablet, taken orally twice a day	Dietary supplement	Placebo, Zoledronic Acid

Primary outcome

Change in Bone Mineral Density of the Lumbar Spine at 12 Months
Time frame: Screening (day -21 to -1) and month 12
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.
Change in Bone Mineral Density of the Total Hip Region at 12 Months
Time frame: Screening (day -21 to -1) and month 12
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.

9 secondary outcomes

Change in Bone Mineral Density of the Lumbar Spine at 6 Months
Time frame: Screening (day -21 to -1) and month 6
Change in Bone Mineral Density of the Femoral Neck at 6 Months
Time frame: Screening (day -21 to -1) and month 6
Change in Bone Mineral Density of the Total Hip at 6 Months
Time frame: Screening (day -21 to -1) and month 6
Change in Bone Mineral Density of the Femoral Neck at 12 Months
Time frame: Screening (day -21 to -1) and month 12
Change in Bone Mineral Density of the Lumbar Spine at 24 Months
Time frame: Screening (day -21 to -1) and month 24
Change in Bone Mineral Density of the Total Hip Region at 24 Months
Time frame: Screening (day -21 to -1) and month 24
Change in Bone Mineral Density of the Femoral Neck at 24 Months
Time frame: Screening (day -21 to -1) and month 24
Course of Disease in Multiple Sclerosis Patients
Time frame: Screening (day -21 to -1) and month 12
Adverse Events and Serious Adverse Events Comparison of Treatment Groups
Time frame: 24 months

Results and safety

Results posted to the registry on 26 Nov 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Zoledronic Acid	21	0
Placebo	8	0

Primary outcome: Change in Bone Mineral Density of the Lumbar Spine at 12 Months

Time frame: Screening (day -21 to -1) and month 12

Population analysed: A total of 168 randomized participants were needed to have a power of 93% % to detect a significant difference in lumbar spine BMD. This study randomized 29 participants of the planned 168; hence, the planned analysis was not done.

Primary outcome: Change in Bone Mineral Density of the Total Hip Region at 12 Months

Time frame: Screening (day -21 to -1) and month 12

9 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Zoledronic Acid	2 of 21 (9.5%)	16 of 21 (76.2%)	Not reported
Placebo	0 of 8 (0%)	5 of 8 (62.5%)	Not reported

Limitations and caveats (from the sponsor): Study termination due to small number of participants recruited lead to lack of power for analysis of all outcome measures.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Osteoporosis

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmceuticals study director

Novartis Pharmaceuticals

15 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Zoledronic Acid and Calcium and Vitamin D combination in people with Osteoporosis and Multiple Sclerosis, run by Novartis at 15 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 26 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Bone Mineral Density of the Lumbar Spine at 12 Months (time frame: Screening (day -21 to -1) and month 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01166178.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2013.