Efficacy Study of Zoledronic Acid and Teriparatide Combination Therapy in Women With Osteoporosis - Full Text View

Purpose

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

Condition	Intervention	Phase
Osteoporosis	Drug: Zoledronic acid Drug: Placebo Drug: Teriparatide	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Bone Density Minerals Osteoporosis

Drug Information available for: Teriparatide Teriparatide acetate Zoledronic acid

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 52 [ Time Frame: Baseline through Week 52 ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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.
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 ] [ Designated as safety issue: No ]
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.
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 ] [ Designated as safety issue: No ]
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.
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 ] [ Designated as safety issue: No ]
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.


Enrollment:	412
Study Start Date:	December 2006
Study Completion Date:	February 2009
Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Zoledronic acid plus teriparatide 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.	Drug: Zoledronic acid 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. Other Name: Reclast, Aclasta Drug: Teriparatide 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. Other Name: Forteo/Forsteo™
Experimental: Zoledronic acid 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.	Drug: Zoledronic acid 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. Other Name: Reclast, Aclasta
Active Comparator: Placebo zoledronic acid plus teriparatide 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.	Drug: Placebo 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 Drug: Teriparatide 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. Other Name: Forteo/Forsteo™

Eligibility


Ages Eligible for Study:	45 Years to 89 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

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

Exclusion criteria:

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
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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00439244

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Sponsors and Collaborators

Novartis

More Information

No publications provided


Responsible Party:	External Affairs, Novartis
ClinicalTrials.gov Identifier:	NCT00439244 History of Changes
Other Study ID Numbers:	CZOL446H2409
Study First Received:	February 22, 2007
Results First Received:	January 5, 2011
Last Updated:	March 23, 2011
Health Authority:	Argentina: National Administration of Drugs, Foods and Medical Technology Belgium: Federal Agency for Medicines and Health Products, FAMHP Germany: Federal Institute for Drugs and Medical Devices Spain: Spanish Agency of Medicines United States: Food and Drug Administration

Keywords provided by Novartis:


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

Additional relevant MeSH terms:


Osteoporosis Bone Diseases Bone Diseases, Metabolic Musculoskeletal Diseases Diphosphonates	Teriparatide Zoledronic acid Bone Density Conservation Agents Pharmacologic Actions Physiological Effects of Drugs

ClinicalTrials.gov processed this record on March 03, 2015