E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Osteoporosis in postmenopausal women |
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E.1.1.1 | Medical condition in easily understood language |
Osteoporosis in postmenopausal women |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10031285 |
E.1.2 | Term | Osteoporosis postmenopausal |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Determine the comparative safety and efficacy of 18 months of treatment with BA058 80 µg on reduction of vertebral fracture incidence in otherwise healthy ambulatory postmenopausal women at risk of fracture from severe osteoporosis when compared with Placebo. |
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E.2.2 | Secondary objectives of the trial |
Determine the comparative efficacy of 18 months of BA058 80 μg treatment in otherwise healthy ambulatory postmenopausal women at risk of fracture from severe osteoporosis:
• on lumbar spine, hip, and femoral neck bone mineral density when compared to teriparatide
• on reduction of non-vertebral fracture incidence when compared with placebo
Determine the overall safety and tolerability of 18 months of BA058 80 μg treatment in otherwise healthy ambulatory postmenopausal women at risk of fracture from severe osteoporosis:
• specifically with respect to number of hypercalcemic events when compared to teriparatide and placebo
Provide additional evidence of safety through:
• bone histomorphometric assessment of bone biopsy samples in a subset of patients in the BA058 80 μg, placebo and Teriparatide groups.
• renal radiological assessment by renal CT scan in a subset of patients from selected centers in the BA058 80 μg, placebo and teriparatide groups
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Bone Bipsy sub study and Renal CT scan sub study |
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E.3 | Principal inclusion criteria |
Inclusion Criteria
• Healthy ambulatory postmenopausal (≥ 5 years) women from 50 to 85 years of age (inclusive) with a diagnosis of osteoporosis
• The women are to have a BMD T score ≤ 2.5 and > -5.0 at the lumbar spine or hip (femoral neck) by dual energy x-ray absorptiometry (DXA) and radiological evidence of 2 or more mild or one or more moderate lumbar or thoracic vertebral fractures, or history of low trauma forearm, humerus, sacral, pelvic, hip, femoral, or tibial fracture within the past 5 years
o Postmenopausal women older than 65 who meet the above fracture criteria but have a T score ≤ 2.0 and > -5.0 may be enrolled. Women older than 65 who do not meet the fracture criteria may also be enrolled if their T score is ≤-3.0 and > -5.0
• Normal physical exam, vital signs, ECG and medical history, with a body mass index (BMI) of 18.5 to 33
• Laboratory tests within the normal range including serum calcium, PTH(1-84), serum phosphorus and alkaline phosphatase
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E.4 | Principal exclusion criteria |
Exclusion Criteria
• History of more than 4 mild or moderate spine fractures or any severe fracture
• Abnormality of the spine or hip that would prohibit assessment of bone mineral density (BMD)
• History of radiotherapy - other than radioiodine
• Unexplained elevation of serum alkaline phosphatase, history of bone disorders (such as Paget’s disease) or a diagnosis of cancer within the last 5 years (with the exception of basal cell or squamous cancer of the skin)
• History of nephrolithiasis or urolithiasis within the past five years, or history of osteosarcoma at any time
• History of thyroid disorders, malabsorptive syndromes or any chronic or recurrent diseases or disturbances that would interfere with the interpretation of study data or compromise the safety of the patient
• Prior treatment with PTH or PTHrP
• Prior treatment with bone acting drugs within the past five years
• Prior treatment with androgens, anabolic steroids, corticosteroids or selective estrogen receptor modulators within the past 12 months
• Prior treatment with an investigational drug within the past 12 months
• Hepatitis B, Hepatitis C, HIV-1 or HIV-2 positive
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of BA058-treated patients showing new vertebral fractures at End-of-Treatment when compared to Placebo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline and at the end-of-trial |
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E.5.2 | Secondary end point(s) |
Determine the comparative efficacy of 18 months of BA058 80 μg treatment in otherwise healthy ambulatory postmenopausal women at risk of fracture from severe osteoporosis:
• on lumbar spine, hip, and femoral neck bone mineral density when compared to teriparatide
• on reduction of non-vertebral fracture incidence when compared with placebo
Determine the overall safety and tolerability of 18 months of BA058 80 μg treatment in otherwise healthy ambulatory postmenopausal women at risk of fracture from severe osteoporosis:
• specifically with respect to number of hypercalcemic events when compared to teriparatide and placebo
Provide additional evidence of safety through:
• bone histomorphometric assessment of bone biopsy samples in a subset of patients in the BA058 80 μg, placebo and Teriparatide groups
• renal radiological assessment by renal CT scan in a subset of patients from selected centers in the BA058 80 μg, placebo and teriparatide groups |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Screening, pre-treatment, baseline, months 1, 3, 6, 9, 12, 15, 18, 19 |
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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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
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
| Yes |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 | No |
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 |
Argentina |
Brazil |
Czech Republic |
Denmark |
Estonia |
Hong Kong |
India |
Lithuania |
Poland |
Romania |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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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 | 3 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 16 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |