E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
A descriptive investigation of adult Danish patients with OI is at the moment being conducted. In this study the underlying genetic background is compared with the phenotype.
The aim of the present study is to investigate the effect of treatment of adult patients with OI with bisphosphonate (zoledronic acid)and parathyroid hormone (PTH) compared with placebo on bone mass, fracture risk and quality of life. The hypothesis is tested in a randomized, placebo controlled, double blind trial.
The following endpoints have been identified:
Primary endpoint:
1. The effect of the treatments on bone mineral density (BMD) at the lumbar spine.
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E.2.2 | Secondary objectives of the trial |
Secondary endpoints:
1. The effect of the treatments on bone mineral density (BMD) at the hip (femoral neck and total hip)
2. The effect of the treatments on fracture risk
3. The effect of the treatments on bone turnover evaluated by biochemical markers before, during and after treatment.
4. The effect of the treatments on bone architecture evaluated by histomorphometry after 2 years treatment.
5. The effect of the treatments on bone architecture investigated by QCT and pQCT before and after 2 years treatment.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inklusion criterias
• Patients with OI type I and IV
• Age 22 - 70 years
• Informed consent
o Low BMD (T-score =/< -1.0) or =/<-1
• For women: ≥ 1 year postmenopausal
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E.4 | Principal exclusion criteria |
Exklusion criterias
• Creatinine clearance < 30 mL/min
• Previous treatment with PTH. Previous treatment with antiresorptives is not an exclusion criteria, but will be used for stratification of the patients
• Treatment with glucocorticoids ≥ 5mg daily during the last 3 months.
• Metabolic bone disease or vitamin D deficiency.
• Liver- or kidney disease
• Existing contra indications for treatment with zoledronic acid or PTH
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint:
1. The effect of the treatments on bone mineral density (BMD) at the lumbar spine.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
DXA evaluation at 6, 12, 18, 24, 30 and 36 months |
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E.5.2 | Secondary end point(s) |
Secondary endpoints:
1. The effect of the treatments on bone mineral density (BMD) at the hip (femoral neck and total hip)
2. The effect of the treatments on fracture risk
3. The effect of the treatments on bone turnover evaluated by biochemical markers before, during and after treatment.
4. The effect of the treatments on bone architecture evaluated by histomorphometry after 1 years treatment.
5. The effect of the treatments on bone architecture investigated by QCT and pQCT before, after 1 year of treatment and after treatment.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
ad 1: DXA evaluation at 6, 12, 18, 24, 30 and 36 months
ad 2: Continuously and at 36 months
ad 3: before, during (at 1, 3, 6, 12, 18, 24 and 30 months) and after treatment.
ad 4: after year 1
ad 5: before treatment, after 1 year of treatment and after treatment.
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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 | Yes |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 11 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |