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

Back to results

Primary Purpose

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Zoledronic acid

Placebo

Teriparatide

About this trial

This is an interventional treatment trial for Osteoporosis focused on measuring 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

Eligibility Criteria

45 Years - 89 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Active Comparator

Arm Label

Zoledronic acid plus teriparatide

Zoledronic acid

Placebo zoledronic acid plus teriparatide

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

Full Information

NCT ID

NCT00439244

First Posted

February 22, 2007

Last Updated

March 23, 2011

Sponsor

Novartis

1. Study Identification

Unique Protocol Identification Number

NCT00439244

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2011

Overall Recruitment Status

Completed

Study Start Date

December 2006 (undefined)

Primary Completion Date

February 2009 (Actual)

Study Completion Date

February 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Novartis

4. Oversight

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

412 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Zoledronic acid plus teriparatide

Arm Type

Active Comparator

Arm Description

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.

Arm Title

Zoledronic acid

Arm Type

Experimental

Arm Description

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.

Arm Title

Placebo zoledronic acid plus teriparatide

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Zoledronic acid

Other Intervention Name(s)

Reclast, Aclasta

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Teriparatide

Other Intervention Name(s)

Forteo/Forsteo™

Intervention Description

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.

Primary Outcome Measure Information:

Title

Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 52

Description

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.

Time Frame

Baseline through Week 52

Secondary Outcome Measure Information:

Title

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

Description

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.

Time Frame

Baseline through Week 13 and Week 26

Title

Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) at Week 13, Week 26 and Week 52

Description

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.

Time Frame

Baseline through Week 13, Week 26 and Week 52

Title

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

Description

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.

Time Frame

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

Title

Bone Resorption and Formation Biochemical Markers : Beta C-terminal Telopeptides of Type I Collagen (β-CTx)

Description

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.

Time Frame

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

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

45 Years

Maximum Age & Unit of Time

89 Years

Accepts Healthy Volunteers

No

Eligibility 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

Facility Information:

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294

Country

United States

City

Beverly Hills

State/Province

California

ZIP/Postal Code

90211

Country

United States

Facility Name

Novartis Investigative Site

City

La Mesa

State/Province

California

Country

United States

Facility Name

Novartis Investigative Site

City

Oakland

State/Province

California

Country

United States

City

Colorado Springs

State/Province

Colorado

ZIP/Postal Code

80910

Country

United States

City

Lakewood

State/Province

Colorado

ZIP/Postal Code

80227

Country

United States

City

Gainesville

State/Province

Georgia

ZIP/Postal Code

30501

Country

United States

City

Morton Grove

State/Province

Illinois

ZIP/Postal Code

60053

Country

United States

City

Urbandale

State/Province

Iowa

ZIP/Postal Code

50322

Country

United States

City

Bangor

State/Province

Maine

ZIP/Postal Code

04401

Country

United States

Facility Name

Novartis Investigative Site

City

Woodbury

State/Province

Minnesota

Country

United States

City

St. Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

City

Lincoln

State/Province

Nebraska

ZIP/Postal Code

68516

Country

United States

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87106

Country

United States

City

West Haverstraw

State/Province

New York

ZIP/Postal Code

10993

Country

United States

Facility Name

Novartis Investigative Site

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15253

Country

United States

Facility Name

Novartis Investigative Site

City

Spokane

State/Province

Washington

Country

United States

City

Madison

State/Province

Wisconsin

ZIP/Postal Code

53705

Country

United States

Facility Name

Novartis Investigative Site

City

Bruxelles

Country

Belgium

Facility Name

Novartis Investigative Site

City

Gent

Country

Belgium

Facility Name

Novartis Investigative site

City

Godinne

Country

Belgium

Facility Name

Novartis Investigative Site

City

Leuven

Country

Belgium

Facility Name

Novartis Investigative Site

City

Liege

Country

Belgium

Facility Name

Novartis Investigative Site

City

Essen

Country

Germany

Facility Name

Novartis Investigative Site

City

Hannover

Country

Germany

Facility Name

Novartis Investigative Site

City

Heidelberg

Country

Germany

Facility Name

Novartis Investigative Site

City

Magdeburg

Country

Germany

Facility Name

Novartis Investigative Site

City

Munchen

Country

Germany

Facility Name

Novartis Investigative site

City

Wuerzburg

Country

Germany

Facility Name

Novartis Investigative Site

City

Barcelona

Country

Spain

Facility Name

Novartis Investigative Site

City

Granada

Country

Spain

Facility Name

Novartis Investigative Site

City

Madrid

Country

Spain

Facility Name

Novartis Investigative Site

City

Valencia

Country

Spain

Osteoporosis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial