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

Osteoporosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00439244
• Other study ID #: CZOL446H2409
• Status: Completed
• Phase: Phase 3
• First received: February 22, 2007
• Last updated: March 23, 2011
• Start date: December 2006
• Est. completion date: February 2009

Study information

• Verified date: March 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: National Administration of Drugs, Foods and Medical TechnologyBelgium: Federal Agency for Medicines and Health Products, FAMHPGermany: Federal Institute for Drugs and Medical DevicesSpain: Spanish Agency of MedicinesUnited States: Food and Drug Administration
• Study type: Interventional

Clinical 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 412
• Est. completion date: February 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 45 Years to 89 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Osteoporosis

Intervention

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.
• 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
• 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.

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative site	Godinne
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Liege
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Munchen
Germany	Novartis Investigative site	Wuerzburg
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Granada
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Valencia
United States	Novartis Investigative Site	La Mesa	California
United States	Novartis Investigative Site	Oakland	California
United States	Novartis Investigative Site	Pittsburgh	Pennsylvania
United States	Novartis Investigative Site	Spokane	Washington
United States	Novartis Investigative Site	Woodbury	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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.	Baseline through Week 13 and Week 26	No
Secondary	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.	Baseline through Week 13, Week 26 and Week 52	No
Secondary	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.	At Baseline, Week 4, Week 8, Week 26, Week 39 and Week 52	No
Secondary	Bone Resorption and Formation Biochemical Markers : Beta C-terminal Telopeptides of Type I Collagen (ß-CTx)	Specialized tests for markers of bone formation such as ß-CTx were performed at Baseline, and Weeks 4, 8, 26, 39, and 52. The amount of serum ß-CTx was determined by the central laboratory.	At Baseline, Week 4, Week 8, Week 26, Week 39 and Week 52	No