Efficacy Study of Zoledronic Acid and Teriparatide Combination Therapy in Women With Osteoporosis

NCT00439244 | Completed Phase 3 Results

• 1 other identifier: CZOL446H2409
• Study Type: interventional
• Target: 412
• Locations: 4 countries
• Sites: 33

Brief 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

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline through Week 52

Secondary Outcomes (4)

• Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 13 and Week 26

  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

  Baseline through Week 13, Week 26 and Week 52

• Bone Resorption and Formation Biochemical Markers : N-terminal Propeptide of Type I Collagen (P1NP)

  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)

  At Baseline, Week 4, Week 8, Week 26, Week 39 and Week 52

Study Arms (3)

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.

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.

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.

Drug: Placebo; Drug: Teriparatide

Interventions

Zoledronic acid DRUG

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.

Also known as: Reclast, Aclasta

Zoledronic acid; Zoledronic acid plus teriparatide

Placebo DRUG

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

Placebo zoledronic acid plus teriparatide

Teriparatide DRUG

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.

Also known as: Forteo/Forsteo™

Placebo zoledronic acid plus teriparatide; Zoledronic acid plus teriparatide

Eligibility Criteria

• Age: 45 Years - 89 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis: lead

Study Sites (33)

Unknown Facility

Birmingham, Alabama, 35294, United States

Location

Unknown Facility

Beverly Hills, California, 90211, United States

Location

Novartis Investigative Site

La Mesa, California, United States

Location

Novartis Investigative Site

Oakland, California, United States

Location

Unknown Facility

Colorado Springs, Colorado, 80910, United States

Location

Unknown Facility

Lakewood, Colorado, 80227, United States

Location

Unknown Facility

Gainesville, Georgia, 30501, United States

Location

Unknown Facility

Morton Grove, Illinois, 60053, United States

Location

Unknown Facility

Urbandale, Iowa, 50322, United States

Location

Unknown Facility

Bangor, Maine, 04401, United States

Location

Novartis Investigative Site

Woodbury, Minnesota, United States

Location

Unknown Facility

St Louis, Missouri, 63110, United States

Location

Unknown Facility

Lincoln, Nebraska, 68516, United States

Location

Unknown Facility

Albuquerque, New Mexico, 87106, United States

Location

Unknown Facility

West Haverstraw, New York, 10993, United States

Location

Novartis Investigative Site

Pittsburgh, Pennsylvania, 15253, United States

Location

Novartis Investigative Site

Spokane, Washington, United States

Location

Unknown Facility

Madison, Wisconsin, 53705, United States

Location

Novartis Investigative Site

Brussels, Belgium

Location

Novartis Investigative Site

Ghent, Belgium

Location

Novartis Investigative site

Godinne, Belgium

Location

Novartis Investigative Site

Leuven, Belgium

Location

Novartis Investigative Site

Liège, Belgium

Location

Novartis Investigative Site

Essen, Germany

Location

Novartis Investigative Site

Hanover, Germany

Location

Novartis Investigative Site

Heidelberg, Germany

Location

Novartis Investigative Site

Magdeburg, Germany

Location

Novartis Investigative Site

München, Germany

Location

Novartis Investigative site

Würzburg, Germany

Location

Novartis Investigative Site

Barcelona, Spain

Location

Novartis Investigative Site

Granada, Spain

Location

Novartis Investigative Site

Madrid, Spain

Location

Novartis Investigative Site

Valencia, Spain

Location

MeSH Terms

Conditions

Osteoporosis; Xanthomatosis, Cerebrotendinous

Interventions

Zoledronic Acid; Teriparatide

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipid Metabolism Disorders; Xanthomatosis

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Parathyroid Hormone; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

No teriparatide placebo available, Short study duration, Only bone mineral data, No bone strength or bone stucture assessment, No bone turnover markers data between 8 and 26 weeks, Study not powered for fracture outcomes.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

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: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 22, 2007
• First Posted: February 23, 2007
• Study Start: December 1, 2006
• Primary Completion: February 1, 2009
• Study Completion: February 1, 2009
• Last Updated: April 20, 2011
• Results First Posted: April 20, 2011

Record last verified: 2011-03

Locations

DE (6); BE (5); ES (4); US (18)