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 post-menopausal women taking calcium and vitamin D

• Register: EUCTR
• Last refreshed on: 7 January 2013
• Main ID: EUCTR2005-000668-17-IT
• Date of registration: 14/03/2006
• Prospective Registration: No
• Primary sponsor: NOVARTIS FARMA
• 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 post-menopausal women taking calcium and vitamin D
• 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 post-menopausal women taking calcium and vitamin D
• Date of first enrolment: 25/05/2005
• Target sample size: 2480
• 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 Number of treatment arms in the trial: 3

Countries of recruitment

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

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion criteria ? Women, 93 years of age and under, inclusive (at the time of randomization in extension study) and 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
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) no
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:
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, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml) ? Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy ? 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 ? Note: Use of corticosteroids in forms such as topical creams, nasal or inhaled formulations or those injected locally (intra-articularly) are NOT exclusionary ? 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


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

Health Condition(s) or Problem(s) studied

Post menopausal osteoporosis
MedDRA version: 14.1 Level: PT Classification code 10031285 Term: Osteoporosis postmenopausal System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Trade Name: aclasta
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Zoledronic acid
Concentration unit: mg milligram(s)
Concentration number: 5-

Primary Outcome(s)

Secondary Objective: Secondary efficacy objectives are: ? 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 in Z6 patients compared to Z3P3 patients. ? To assess the relative change in biochemical markers of bone turnover at Year 4.5 and 6 relative to Year 3 in Z6 patients compared to Z3P3 patients. ? PLS see protocol

Primary end point(s): 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).

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)

2005-000668-17-HU

CZOL446H2301E1