A 3 year, double-blind extension to CZOL446H2301 to evaluate the long term safety and efficacy of zoledronic acid in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D. - 2301 E1

• Register: EUCTR
• Last refreshed on: 3 July 2012
• Main ID: EUCTR2005-000668-17-HU
• Date of registration: 17/05/2005
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A 3 year, double-blind extension to CZOL446H2301 to evaluate the long term safety and efficacy of zoledronic acid in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D. - 2301 E1
• Scientific title: A 3 year, double-blind extension to CZOL446H2301 to evaluate the long term safety and efficacy of zoledronic acid in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D. - 2301 E1
• Date of first enrolment: 12/07/2005
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-000668-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Finland, Germany, Hungary, Italy, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
•Women, 93 years of age and under, inclusive (at the time of randomization in extension study) who have received 3 infusions of study medication in the core study according to the guidelines and instructions provided.

•Signed written informed consent to participate in the extension study

•Patients must be considered ambulatory. Patients can be included who are ambulatory with an assistive device (cane, walker, etc)

•Patients must have been taking the dosage of calcium and vitamin D required in the core study (1000 to 1500 mg of elemental calcium and 400 to 1200 IU of vitamin D daily) for at least 3 months prior to entry into the extension and have a serum calcium within the normal range at baseline

•Patients must have DXA measurements of the hip performed at Visit 7 (final core study visit)

• Patients must be randomized into the extension study at Visit 8 between 10 and 18 months after receiving their third dose of study medication in the core study at Visit 6

Additional Inclusion Criteria for Bone Biopsy Subset (up to 60
patients)

• Patients must have received three doses of study drug in this extension study to be eligible
• Signed written informed consent to participate in the bone biopsy subset

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
•Patients who demonstrated a major protocol violation in the core study or patients for whom the investigator feels participation in the extension study is not appropriate

•Pregnant or nursing (lactating) women

•Women of child-bearing potential (WOCBP)

•Any prior use of iv bisphosphonate other than the study drug during the core study and during the period after completion of the core study but prior to randomization in the extension study

•Any use of oral bisphosphonates for more than 1 month total during the core study and during the period after completion of the core study but prior to randomization in the extension study

•Any prior use of PTH for more than 1 month during the core study and during the period after completion of the core study but prior to randomization in the extension study

•Use of systemic corticosteroids (oral or i.v.) at an average dose of greater than or equal to 7.5 mg per day of oral prednisone or equivalent for a period of three months just prior to entering the extension

•Any use of anabolic steroids or growth hormone for more than 3 months just prior to entering the extension

•Any prior use of strontium (all formulations)

•Any use of sodium fluoride for osteoporosis during the core study and during the period after completion of the core study but prior to randomization in the extension study

•Serum calcium less than 8 mg/dL (2.0 mmol/L) at Visit 7 (final core study visit) or at a subsequent pre-dose laboratory test prior to randomization in the extension study

•Serum calcium greater than 11.0 mg/dL (2.75 mmol/L) at Visit 7 (final core study visit) or at a subsequent pre-dose laboratory test prior to randomization in the extension study

•Active primary hyperparathyroidism

•Surgery to the thyroid or parathyroids resulting in partial or complete hypoparathyroidism

•Uncontrolled seizure disorders associated with falls

•Bilateral hip replacement or bilateral hip surgery with implantation of an appliance during the core study

•Cancer exclusions:
•Patients with a new diagnosis or active treatment for cancer during the course of the core study.
•Patients using tamoxifen or aromatase inhibitors for a recent or active cancer
•Patients with metastases (or with a history of metastases)
•Patients with a history of radiation therapy to the head or neck area
•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, Ductal Carcinoma in-situ (DCIS) that has been surgically removed, and Carcinoma in-situ (CIS) of the uterine cervix that has been surgically removed.

•Multiple myeloma or Paget’s disease diagnosed or discovered during the core study

•Occurrence of iritis or uveitis except when secondary to trauma during the core study and during the period after completion of the core study but prior to randomization in the extension study

•History of diabetic nephropathy or retinopathy or uncontrolled diabetes (e.g. patients with a history of HbA1c > 10%).

•AST or ALT greater than twice the upper limit of normal at Visit 7 (final core study visit) or at a subsequent pre-dose laboratory test prior to randomization in the extension study

•Alkaline phosphatase greater than 1.5 times the upper limit of normal at Visit 7 (final core study visit) or at a subsequent pre-dose laboratory test prior to randomization in the extension study

•Renal insufficiency with a calculated creatinine clearance les

Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Osteoporosis in postmenopausal women
MedDRA version: 9.1 Level: LLT Classification code 10031282 Term: Osteoporosis

Intervention(s)

Trade Name: Aclasta
Product Name: Aclasta
Product Code: ZOL446H
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: zoledronic acid
Current Sponsor code: ZOL446H
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): Percent change in BMD of the femoral neck at Year 6 relative to Year 3 in Z6 patients compared to Z3P3 patients.

Secondary Objective: •To assess the percent changes in BMD of the femoral neck, total hip, and trochanter at Year 4.5 and Year 6 relative to Year 0 in Z6 patients compared to Z3P3 patients.

•To assess the percent changes in BMD of the femoral neck, total hip, and trochanter at Year 4.5 relative to Year 3 in Z6 patients compared to Z3P3 patients.

•To assess the percent changes in BMD of the total hip and trochanter at Year 6 relative to Year 3 in Z6 patients compared to Z3P3 patients.

•To assess the relative change in biochemical markers of bone turnover at Year 4.5 and Year 6 relative to Year 0 and Year 3 in Z6 patients compared to Z3P3 patients.

•To assess the relative change in biochemical markers of bone turnover at Year 3.5, 4, 4.5, 5, and 6 relative to Year 0 and Year 3 in a subset of approximately 200 Z6 and Z3P3 patients who participated in this subset in the core study.

Main Objective: To assess the percent change in BMD of the femoral neck as measured by DXA at Year 6 relative to Year 3 in patients treated with zoledronic acid for up to 6 years in the CZOL446H2301 core and extension studies (Group Z6) compared to patients treated with zoledronic acid for 3 years in the CZOL446H2301 core study followed by up to 3 years of placebo in the CZOL446H2301 extension study (Group Z3P3).

Secondary ID(s)

CZOL446H2301 E1