E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Information not present in EudraCT |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
to examine the long-term safety of two different dosage regiments of zoledronic acid over an additional 12 months in pediatric patients who have completed one-year of treatment of zoledronic acid in the core CZOL446H2202 study, with focus on general safety and renal safety. |
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E.2.2 | Secondary objectives of the trial |
to assess continued efficacy, compared to baseline (visit 1 of core) : • % change in lumbar spine bone mineral density at mo 18 & 24 • change in Z score of lumbar spine at mo18 & 24 • # clinical fractures per patient over 12-mo ext & 24-mo total • change in bone resorption / formation markers at mo15, 18, 21 & 24 • change in supine length/height at mo 15, 18, 21 & 24 • change in bone pain • change in bone mineral content of total body at mo 18 & 24 • change in cortical bone thickness at mo 24 • change in vertebral spine length at mo 24 • change in grip strength at mo 15, 18, 21 & 24 • % of patients need treatment before scheduled dosing visits during the extension |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
• Children, male or female, between 1 year and 17 years of age at visit 1 of the extension, all inclusive, who have completed 1 year treatment of zoledronic acid or pamidronate in CZOL446H2202 trial. |
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E.4 | Principal exclusion criteria |
• Any disease or planned therapy which will interfere with the procedures or data collection of this trial. • Any disease or abnormality that would prevent accurate bone-mineral density measurements of the lumbar spine (e.g., intra-abdominal calcification that may prohibit accurate data collection/interpretation; severe scoliosis, kyphosis, or metal implants, etc.) • Any surgical bone-lengthening procedure, e.g. Ilizarov procedure planned/scheduled to occur during the trial. • Female patients of child-bearing potential are eligible only if they are: not pregnant (serum β-hCG pregnancy-test negative)/non-lactating; are sexually abstinent or are surgically sterile (tubal ligation or hysterectomy): and if sexually active, must be practicing a medically acceptable form of birth control, defined as the use of an IUD, a barrier method with spermicide, condoms, subdermal implant or oral contraceptives. Females of child-bearing potential who are sexually active must agree to continue to practice their birth control during the trial and at least 1 year after completing the trial and must consent to a pregnancy test prior to every dose administration. • Renal abnormality (please see section 7.5.1): defined as a serum-creatinine value above the upper limit of normal (age- and sex-matched) or a urine dipstick greater than 2 + protein. • Hypocalcemia: any value (age-matched) below the normal range. • History or evidence of an intestinal malabsorption syndrome. • Patients with a significant drug-related adverse event in the original protocol. • Patients who discontinued treatment in the original protocol ZOL446H2202.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Bone-mineral density (BMD) measurements (lumbar spine and total body) by dual energy absorptiometry (DEXA) • X-rays of the vertebral spine and the left hand: to determine vertebral spine length, bone cortical thickness and number of clinical fractures. • Specialized serum tests to evaluate bone resorption and formation will be performed for C-telopeptide (CTX), N-terminal propeptide of type I collagen (P1NP), parathyroid hormone (PTH) and bone specific alkaline phosphatase (SAP). • Bone Pain Assessment using the pediatric Wong-Baker FACES Pain Rating Scale. • Grip Strength using dynamometry • Clinical fractures • Height using stadiometer • Incidence of patients who need treatment before scheduled dosing visit.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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if the trial is endangering the safety of the patients |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |