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Intervenous (IV) Zoledronic Acid After Forteo in Postmenopausal Women

Primary Purpose

Osteoporosis

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
zoledronic acid
Sponsored by
The Cleveland Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteoporosis focused on measuring osteoporosis, zoledronic acid, forteo

Eligibility Criteria

undefined - 85 Years (Child, Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Postmenopausal women to age 85, inclusive Finish treatment of 12 months or longer with Forteo Signed informed consent prior to initiation of any study-mandated procedure. Exclusion Criteria: Hip and spine DXA T-score >-1.0 Patients with 25-(OH) vitamin D levels less than 15 ng/mL at Visit 1. (Patient can be repleted with vitamin D 50,000 units biweekly for up to 2 months and re-screened anytime during the 2 months while continuing Forteo.) Baseline renal insufficiency (calculated creatinine clearance less than 40.0 mL/min (MDRD) at Visit 1 and/or Visit 2 or urine dipstick greater than or equal to 2+ protein without evidence of contamination or bacteriuria (may be repeated one time at least a week apart if there is suspicion of contamination). Patients with calculated creatinine clearance equal to or greater than 40.0 mL/min and less than 60.0 mL/min or serum creatinine greater than the upper limit of normal at Visit 1 must be retested between Visit 1 and 2. Patients with calculated creatinine clearance greater than 60.0 mL/min and serum creatinine within normal limits at Visit 1 do not require re-test. Patients who require re-test of creatinine clearance between Visit 1 and 2 will be excluded if there is an increase in serum creatinine greater than 0.5 mg/dL between Visit 1 and Visit 2. Serum calcium <8.5 or >11.0 mg/dl at Visit 1 AST or ALT greater than twice the upper limit of normal Serum alkaline phosphatase greater than 1.5 times the upper limit of normal (liver fraction) No history of retinopathy or nephropathy especially in the presence of uncontrollable IDDM with Hb1 AC > 10% Hypersensitivity to bisphosphonates Treatment with biphosphonates while on Forteo Prior treatment with i.v. biphosphonates Estrogen, calcitonin, raloxifene use prior to Forteo treatment are not exclusions, but concomitant therapy during with any bone agents during the trial will not be permitted Any prior use of strontium ranelate or sodium fluoride Chronic use of systemic corticosteroids (oral or i.v.) within the last year: NOTE: Use of corticosteroids in forms such as topical creams, nasal or inhaled formulations or those injected locally (intra-articularly) are NOT exclusionary. Prior exposure to anabolic steroids or growth hormone within 6 months prior to randomization Treatment with any investigational drug(s) and/or devices within 30 days prior to randomization. History of iritis or uveitis, except when secondary to trauma, and must have resolved for more than 2 years prior to randomization. Cancer exclusions: Patients with a new diagnosis or active treatment for any malignancy less than or equal to 12 months prior to Visit 1. Patients with evidence of any metastases on or prior to randomization, or with a history of metastases Subjects with evidence of paraneoplastic syndrome, especially those characterized by hypercalcemia during screening or by history Patients with the following may be included: basal cell or squamous cell carcinoma of the skin, colonic polyps with non-invasive malignancy which have been removed, and Carcinoma in-situ (CIS) of the prostate (Stage I only) that has been surgically removed. Previous major solid organ or bone marrow transplant recipient or on a transplant waiting list Any disease of the spine that would preclude the proper acquisition of a lumbar spine DXA (L1-L4) e.g., implantable devices, scoliosis, ankylosing spondylitis, DJD. (Less than two lumbar spine vertebral bodies evaluable) Active primary hyperparathyroidism or hypoparathyroidism Subject with complete thyroidectomy Active hyperthyroidism Hypothyroidism not treated with adequate replacement therapy History of multiple myeloma or Paget's disease Patients with severe dental problems or current dental infections, or with recent or impending dental surgery within three months of dosing Any medical or psychiatric condition which, in the opinion of the investigator, would preclude the participant from adhering to the protocol or completing the trial per protocol

Sites / Locations

  • The Cleveland Clinic Foundation

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

open label

Arm Description

5 mg zoledronic acid in a single 15 minute IV

Outcomes

Primary Outcome Measures

Change in Lumbar Spine BMD (Bone Mineral Density) in g/cm^2 From Baseline to Month 12 Relative to Baseline as Measured by DXA (Dual-energy X-ray Absorptiometry)

Secondary Outcome Measures

Change in Bone Density (Grams/cm^2) at the Total Hip at 6 and 12 Months
Change in bone density (grams/cm^2) at the total hip at 6 and 12 months. 12 month reported based on usual interval for bone density follow-up in clinical practice.
Change in Serum C-telopeptide Type 1 Collagen (CTX) (at Day 10 and Months 2, 6, 9 and 12)
Change in serum c-telopeptide type 1 collagen (CTX) (at day 10 and months 2, 6, 9 and 12. 12 month values reported based on 12 month duraton of zolendronic acid effect.
Change in Serum N-propeptide Type 1 Collagen (P1NP) (at Day 10 and Months 2, 6, 9 and 12)
Change in serum n-propeptide type 1 collagen (P1NP) (at day 10 and months 2, 6, 9 and 12. 12 month values reported based on 12 month duraton of zolendronic acid effect.

Full Information

First Posted
August 4, 2006
Last Updated
March 23, 2017
Sponsor
The Cleveland Clinic
Collaborators
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00361595
Brief Title
Intervenous (IV) Zoledronic Acid After Forteo in Postmenopausal Women
Official Title
Open Label Proof of Concept Study of IV Zoledronic Acid (ZA) 5 mg After Forteo in Postmenopausal Women
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
August 2006 (undefined)
Primary Completion Date
April 2008 (Actual)
Study Completion Date
April 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Cleveland Clinic
Collaborators
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to evaluate the adequacy of zoledronic acid in maintaining bone mass after two years of treatment with Forteo, in postmenopausal women.
Detailed Description
This will be a single center open label proof of concept study, recruiting subjects previously treated with Forteo for at least 12 months. A screening period of 3 to 6 weeks will precede the treatment period. At the baseline visit, patients whose eligibility is confirmed will be treated with ZA and followed for 12 months. Safety and efficacy will be assessed at regular intervals (day one, day 10, month 2, month 6, month 9 and month 12). Renal safety will be assessed prior to the i.v. dose of study medication, day 10 after the i.v. dose of study medication and at 12 months. Bone density at the lumbar spine (L1-4) and total hip will be performed at 6 months and at the end of the 12 month treatment period. Biomarker analyses for secondary endpoint will be performed for at day 10, month 2, month 6, month 9 and month 12.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoporosis
Keywords
osteoporosis, zoledronic acid, forteo

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
open label
Arm Type
Experimental
Arm Description
5 mg zoledronic acid in a single 15 minute IV
Intervention Type
Drug
Intervention Name(s)
zoledronic acid
Other Intervention Name(s)
zometa
Intervention Description
5 mg zoledronic acid administered in a single 15 minute IV
Primary Outcome Measure Information:
Title
Change in Lumbar Spine BMD (Bone Mineral Density) in g/cm^2 From Baseline to Month 12 Relative to Baseline as Measured by DXA (Dual-energy X-ray Absorptiometry)
Time Frame
Baseline and 12 months
Secondary Outcome Measure Information:
Title
Change in Bone Density (Grams/cm^2) at the Total Hip at 6 and 12 Months
Description
Change in bone density (grams/cm^2) at the total hip at 6 and 12 months. 12 month reported based on usual interval for bone density follow-up in clinical practice.
Time Frame
6 months and 12 months
Title
Change in Serum C-telopeptide Type 1 Collagen (CTX) (at Day 10 and Months 2, 6, 9 and 12)
Description
Change in serum c-telopeptide type 1 collagen (CTX) (at day 10 and months 2, 6, 9 and 12. 12 month values reported based on 12 month duraton of zolendronic acid effect.
Time Frame
12 months
Title
Change in Serum N-propeptide Type 1 Collagen (P1NP) (at Day 10 and Months 2, 6, 9 and 12)
Description
Change in serum n-propeptide type 1 collagen (P1NP) (at day 10 and months 2, 6, 9 and 12. 12 month values reported based on 12 month duraton of zolendronic acid effect.
Time Frame
12 months

10. Eligibility

Sex
Female
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Postmenopausal women to age 85, inclusive Finish treatment of 12 months or longer with Forteo Signed informed consent prior to initiation of any study-mandated procedure. Exclusion Criteria: Hip and spine DXA T-score >-1.0 Patients with 25-(OH) vitamin D levels less than 15 ng/mL at Visit 1. (Patient can be repleted with vitamin D 50,000 units biweekly for up to 2 months and re-screened anytime during the 2 months while continuing Forteo.) Baseline renal insufficiency (calculated creatinine clearance less than 40.0 mL/min (MDRD) at Visit 1 and/or Visit 2 or urine dipstick greater than or equal to 2+ protein without evidence of contamination or bacteriuria (may be repeated one time at least a week apart if there is suspicion of contamination). Patients with calculated creatinine clearance equal to or greater than 40.0 mL/min and less than 60.0 mL/min or serum creatinine greater than the upper limit of normal at Visit 1 must be retested between Visit 1 and 2. Patients with calculated creatinine clearance greater than 60.0 mL/min and serum creatinine within normal limits at Visit 1 do not require re-test. Patients who require re-test of creatinine clearance between Visit 1 and 2 will be excluded if there is an increase in serum creatinine greater than 0.5 mg/dL between Visit 1 and Visit 2. Serum calcium <8.5 or >11.0 mg/dl at Visit 1 AST or ALT greater than twice the upper limit of normal Serum alkaline phosphatase greater than 1.5 times the upper limit of normal (liver fraction) No history of retinopathy or nephropathy especially in the presence of uncontrollable IDDM with Hb1 AC > 10% Hypersensitivity to bisphosphonates Treatment with biphosphonates while on Forteo Prior treatment with i.v. biphosphonates Estrogen, calcitonin, raloxifene use prior to Forteo treatment are not exclusions, but concomitant therapy during with any bone agents during the trial will not be permitted Any prior use of strontium ranelate or sodium fluoride Chronic use of systemic corticosteroids (oral or i.v.) within the last year: NOTE: Use of corticosteroids in forms such as topical creams, nasal or inhaled formulations or those injected locally (intra-articularly) are NOT exclusionary. Prior exposure to anabolic steroids or growth hormone within 6 months prior to randomization Treatment with any investigational drug(s) and/or devices within 30 days prior to randomization. History of iritis or uveitis, except when secondary to trauma, and must have resolved for more than 2 years prior to randomization. Cancer exclusions: Patients with a new diagnosis or active treatment for any malignancy less than or equal to 12 months prior to Visit 1. Patients with evidence of any metastases on or prior to randomization, or with a history of metastases Subjects with evidence of paraneoplastic syndrome, especially those characterized by hypercalcemia during screening or by history Patients with the following may be included: basal cell or squamous cell carcinoma of the skin, colonic polyps with non-invasive malignancy which have been removed, and Carcinoma in-situ (CIS) of the prostate (Stage I only) that has been surgically removed. Previous major solid organ or bone marrow transplant recipient or on a transplant waiting list Any disease of the spine that would preclude the proper acquisition of a lumbar spine DXA (L1-L4) e.g., implantable devices, scoliosis, ankylosing spondylitis, DJD. (Less than two lumbar spine vertebral bodies evaluable) Active primary hyperparathyroidism or hypoparathyroidism Subject with complete thyroidectomy Active hyperthyroidism Hypothyroidism not treated with adequate replacement therapy History of multiple myeloma or Paget's disease Patients with severe dental problems or current dental infections, or with recent or impending dental surgery within three months of dosing Any medical or psychiatric condition which, in the opinion of the investigator, would preclude the participant from adhering to the protocol or completing the trial per protocol
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chad Deal, MD
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Intervenous (IV) Zoledronic Acid After Forteo in Postmenopausal Women

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