OsteoporosisPhase 3NCT00439244
Efficacy Study of Zoledronic Acid and Teriparatide Combination Therapy in Women With Osteoporosis
A Phase 3 study testing Zoledronic acid and Teriparatide in people with Osteoporosis, run by Novartis at 33 sites in 4 countries.
Trial summary
The purpose of this study is to assess the effects of zoledronic acid administered at the same time with teriparatide compared to zoledronic acid alone and teriparatide alone on bone mineral density (BMD) gain in the lumbar spine and total hip Read more about this study
- Who is it for?
- Ages 45 to 89 years, women only
- Conditions the study is for
- Osteoporosis
- What is being tested?
- Zoledronic acid and Teriparatide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 412 participants
- Where
- 33 sitesin 4 countries
- Study dates
- Dec 2006to Feb 2009
- 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 45 to 89 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Postmenopausal (PMO) women between 45 and 89 years of age.
- Bone mineral density T score of -2.5 or less at femoral neck, total hip or lumbar spine OR
- Bone mineral density T score of -2.0 or less at femoral neck, total hip or lumbar spine with at least one documented osteoporotic vertebral fracture or a previously documented history of an osteoporotic clinical non-vertebral fracture not due to excessive trauma
Who cannot join
- Any prior use of strontium
- Any past or active kidney disease or problems with kidney function
- Prior treatment with any intravenous (i.v.) or oral bisphosphonate (such as but not limited to alendronate, risedronate and pamidronate) longer than 3 months consecutively. If bisphosphonate exposure is less than or equal to 3 months , a washout period of 1 year to randomization is required
- Calcium levels in blood within the normal range
- Normal liver function
- Non-osteoporotic forms of metabolic bone disease such as and not limited to Paget's disease of bone, osteomalacia, osteogenesis imperfecta or multiple myeloma
Show all 10Show fewer
- Less than 3 evaluable lumbar (L1-L4) vertebrae for dual energy x-ray absorptiometry (DXA) measurement
- Treatment with osteoporotic therapies such as raloxifene, calcitonin or Hormone Replacement Therapy within 3 months of randomization
- Allergy or previous exposure to teriparatide
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
33 sites in 4 countries.
33 sites in 4 countries
United States18 sites
Study site
Albuquerque, New Mexico, 87106
Study site
Bangor, Maine, 04401
Study site
Beverly Hills, California, 90211
Study site
Birmingham, Alabama, 35294
Study site
Colorado Springs, Colorado, 80910
Study site
Gainesville, Georgia, 30501
Novartis Investigative Site
La Mesa, California
Study site
Lakewood, Colorado, 80227
Study site
Lincoln, Nebraska, 68516
Study site
Madison, Wisconsin, 53705
Study site
Morton Grove, Illinois, 60053
Novartis Investigative Site
Oakland, California
Novartis Investigative Site
Pittsburgh, Pennsylvania, 15253
Novartis Investigative Site
Spokane, Washington
Study site
St Louis, Missouri, 63110
Study site
Urbandale, Iowa, 50322
Study site
West Haverstraw, New York, 10993
Novartis Investigative Site
Woodbury, Minnesota
Germany6 sites
Novartis Investigative Site
Essen
Novartis Investigative Site
Hanover
Novartis Investigative Site
Heidelberg
Novartis Investigative Site
Magdeburg
Novartis Investigative Site
München
Novartis Investigative site
Würzburg
Belgium5 sites
Novartis Investigative Site
Brussels
Novartis Investigative Site
Ghent
Novartis Investigative site
Godinne
Novartis Investigative Site
Leuven
Novartis Investigative Site
Liège
Spain4 sites
Novartis Investigative Site
Barcelona
Novartis Investigative Site
Granada
Novartis Investigative Site
Madrid
Novartis Investigative Site
Valencia
About this study
Official title: A One-year Partial Double-blinded, Randomized, Multi-center, Multi-national Study to Assess the Effects of Combination Therapy of Annual Zoledronic Acid (5 mg) and Daily Subcutaneous Teriparatide (2mcrg) on Postmenopausal Women With Severe Osteoporosis
The purpose of this study is to assess the effects of zoledronic acid administered at the same time with teriparatide compared to zoledronic acid alone and teriparatide alone on bone mineral density (BMD) gain in the lumbar spine and total hip
- Conditions
- Osteoporosis
- Being tested
- Zoledronic acid, Placebo, Teriparatide
- Keywords
- Bone Mineral Density (BMD), C-Telopeptides (CTx), dual x-ray absorptiometry (DXA), pro-collagen type 1 N-propeptide (P1NP), teriparatide, zoledronic acid, Osteoporosis, postmenopausal women
- Medical subject headings
- Osteoporosis, Xanthomatosis, Cerebrotendinous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zoledronic acidDrug
Also called Reclast, Aclasta
Zoledronic acid 5.0 mg in a ready-to-infuse plastic bottle with a total fill volume of 103 mL to allow an infusion of 100 mL total volume corresponding to 5 mg of zoledronic acid.
PlaceboDrug
Zoledronic acid matched placebo as a 103 mL solution of sterile water (physiologic 0.9% normal saline) to allow an infusion of 100 mL total volume in a ready-to-infuse plastic bottle
TeriparatideDrug
Also called Forteo/Forsteo™
Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. Each pre-filled delivery device is filled with 3.3 mL to deliver 3 mL.
Each mL contains 250 μg teriparatide (corrected for acetate, chloride, and water content), 0.41 mg glacial acetate acid, 0.10 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3.0 mg Metacresol, and water for injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4. Each cartridge pre-assembled into a pen device delivers 20 μg of teriparatide per dose each day for up to 28 days.
| Study group | Role | What they receive |
|---|---|---|
| Zoledronic acid plus teriparatide | Active comparator | Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion. Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks. Receives: Drug: Zoledronic acid; Drug: Teriparatide |
| Zoledronic acid | Experimental | Zoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion. Receives: Drug: Zoledronic acid |
| Placebo zoledronic acid plus teriparatide | Active comparator | Placebo zoledronic acid 100 mL intravenous (i.v.) (once at randomization) plus teriparatide 20 μg (daily subcutaneous injections administered concurrently through 52 weeks). Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks. Receives: Drug: Placebo; Drug: Teriparatide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 52
BMD measurements of the lumbar spine (L1-L4) by Dual X-ray absorptiometry (DXA) were performed on all patients at screening, and Weeks 13, 26, and 52 (or early termination). Every attempt was made to obtain the BMD measurements at the scheduled visit. If this was not possible, a BMD measurement ± 7 days from the scheduled visit was obtained. For the Final DXA at Week 52, the window was 10 - 15 days prior to the final study visit. BMD scans were acquired locally and all results sent to a central reader for evaluation.
Measured: Baseline through Week 52
Secondary outcomes (4)
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 13 and Week 26
BMD measurements of the lumbar spine (L1-L4) by Dual X-ray absorptiometry (DXA) were performed on all patients at screening, and Weeks 13, 26, and 52 (or early termination). Every attempt was made to obtain the BMD measurements at the scheduled visit. If this was not possible, a BMD measurement ± 7 days from the scheduled visit was obtained. For the Final DXA at Week 52, the window was 10 - 15 days prior to the final study visit. BMD scans were acquired locally and all results sent to a central reader for evaluation.
Measured: Baseline through Week 13 and Week 26
Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) at Week 13, Week 26 and Week 52
BMD measurements of the total hip by Dual X-ray absorptiometry (DXA) were performed on all patients at screening, and Weeks 13, 26, and 52 (or early termination). Every attempt was made to obtain the BMD measurements at the scheduled visit. If this was not possible, a BMD measurement ± 7 days from the scheduled visit was obtained. For the final DXA at Week 52, the window was 10 - 15 days prior to the final study visit. BMD scans were acquired locally and all results sent to a central reader for evaluation.
Measured: Baseline through Week 13, Week 26 and Week 52
Bone Resorption and Formation Biochemical Markers : N-terminal Propeptide of Type I Collagen (P1NP)
Specialized tests for markers of bone formation such as n-terminal propeptide of type I collagen (P1NP) were performed at Baseline, and Weeks 4, 8, 26, 39, and 52. The amount of serum P1NP was determined by the central laboratory.
Measured: At Baseline, Week 4, Week 8, Week 26, Week 39 and Week 52
Bone Resorption and Formation Biochemical Markers : Beta C-terminal Telopeptides of Type I Collagen (β-CTx)
Specialized tests for markers of bone formation such as β-CTx were performed at Baseline, and Weeks 4, 8, 26, 39, and 52. The amount of serum β-CTx was determined by the central laboratory.
Measured: At Baseline, Week 4, Week 8, Week 26, Week 39 and Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2007 (estimated)
- Study startDec 2006
- Primary completionFeb 2009
- Study completionFeb 2009
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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 412 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis
- Sponsor type
- Industry (pharma, biotech, devices)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00439244
- Sponsor's protocol ID
- CZOL446H2409
- Status last verified
- Mar 2011
- First submitted
- 22 Feb 2007
- Last updated
- 20 Apr 2011
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A One-year Partial Double-blinded, Randomized, Multi-center, Multi-national Study to Assess the Effects of Combination Therapy of Annual Zoledronic Acid (5 mg) and Daily Subcutaneous Teriparatide (2mcrg) on Postmenopausal Women With Severe Osteoporosis
- ClinicalTrials.gov ID
- NCT00439244
- Acronym / sponsor ID
- CZOL446H2409
- Conditions
- Osteoporosis
- Keywords
- Bone Mineral Density (BMD), C-Telopeptides (CTx), dual x-ray absorptiometry (DXA), pro-collagen type 1 N-propeptide (P1NP), teriparatide, zoledronic acid, Osteoporosis, postmenopausal women
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 412 participants (actual)
- Lead sponsor
- NovartisIndustry (pharma, biotech, devices)
- Study start
- Dec 2006
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 23 Feb 2007 (estimated)
- Results
- Posted 20 Apr 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the effects of zoledronic acid administered at the same time with teriparatide compared to zoledronic acid alone and teriparatide alone on bone mineral density (BMD) gain in the lumbar spine and total hip
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Zoledronic acid plus teriparatide | Active comparator | Drug: Zoledronic acid, Drug: TeriparatideZoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion. Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks. |
| Zoledronic acid | Experimental | Drug: Zoledronic acidZoledronic acid 5.0 mg/100 mL was administered via a peripheral intravenous site at Visit 2 (once at randomization) as a slow 15-minute infusion. |
| Placebo zoledronic acid plus teriparatide | Active comparator | Drug: Placebo, Drug: TeriparatidePlacebo zoledronic acid 100 mL intravenous (i.v.) (once at randomization) plus teriparatide 20 μg (daily subcutaneous injections administered concurrently through 52 weeks). Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. The pen device delivers 20 μg of teriparatide concurrently as daily subcutaneous injections for 52 weeks. |
Who may qualify
- Ages
- 45 to 89 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Postmenopausal (PMO) women between 45 and 89 years of age.
- Bone mineral density T score of -2.5 or less at femoral neck, total hip or lumbar spine OR
- Bone mineral density T score of -2.0 or less at femoral neck, total hip or lumbar spine with at least one documented osteoporotic vertebral fracture or a previously documented history of an osteoporotic clinical non-vertebral fracture not due to excessive trauma
Key exclusion criteria (10 listed)
- Any prior use of strontium
- Any past or active kidney disease or problems with kidney function
- Prior treatment with any intravenous (i.v.) or oral bisphosphonate (such as but not limited to alendronate, risedronate and pamidronate) longer than 3 months consecutively. If bisphosphonate exposure is less than or equal to 3 months , a washout period of 1 year to randomization is required
- Calcium levels in blood within the normal range
- Normal liver function
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 acidAlso: Reclast, AclastaZoledronic acid 5.0 mg in a ready-to-infuse plastic bottle with a total fill volume of 103 mL to allow an infusion of 100 mL total volume corresponding to 5 mg of zoledronic acid. | Drug | Zoledronic acid, Zoledronic acid plus teriparatide |
| PlaceboZoledronic acid matched placebo as a 103 mL solution of sterile water (physiologic 0.9% normal saline) to allow an infusion of 100 mL total volume in a ready-to-infuse plastic bottle | Drug | Placebo zoledronic acid plus teriparatide |
| TeriparatideAlso: Forteo/Forsteo™Teriparatide is supplied as sterile, colorless clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable pen device for subcutaneous injection. Each pre-filled delivery device is filled with 3.3 mL to deliver 3 mL. Each mL contains 250 μg teriparatide (corrected for acetate, chloride, and water content), 0.41 mg glacial acetate acid, 0.10 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3.0 mg Metacresol, and water for injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4. Each cartridge pre-assembled into a pen device delivers 20 μg of teriparatide per dose each day for up to 28 days. | Drug | Placebo zoledronic acid plus teriparatide, Zoledronic acid plus teriparatide |
Primary outcome
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 52
Time frame: Baseline through Week 52
BMD measurements of the lumbar spine (L1-L4) by Dual X-ray absorptiometry (DXA) were performed on all patients at screening, and Weeks 13, 26, and 52 (or early termination). Every attempt was made to obtain the BMD measurements at the scheduled visit. If this was not possible, a BMD measurement ± 7 days from the scheduled visit was obtained. For the Final DXA at Week 52, the window was 10 - 15 days prior to the final study visit. BMD scans were acquired locally and all results sent to a central reader for evaluation.
4 secondary outcomes
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 13 and Week 26
Time frame: Baseline through Week 13 and Week 26
Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) at Week 13, Week 26 and Week 52
Time frame: Baseline through Week 13, Week 26 and Week 52
Bone Resorption and Formation Biochemical Markers : N-terminal Propeptide of Type I Collagen (P1NP)
Time frame: At Baseline, Week 4, Week 8, Week 26, Week 39 and Week 52
Bone Resorption and Formation Biochemical Markers : Beta C-terminal Telopeptides of Type I Collagen (β-CTx)
Time frame: At Baseline, Week 4, Week 8, Week 26, Week 39 and Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
The record lists no contact. Use the official record to reach the sponsor.
33 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Zoledronic acid and Teriparatide in people with Osteoporosis, run by Novartis at 33 sites in 4 countries.
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 3 inclusion and 10 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: finished, as of the sponsor's last update on 20 Apr 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in United States, Germany, Belgium, Spain. 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. 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 20 Apr 2011). 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?
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 52 (time frame: Baseline through Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Apr 2011.