E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Osteoporosis in postmenopausal women |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 |
|
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 |
To determine the clinical safety and efficacy of BA058 Transdermal in otherwise healthy postmenopausal women with osteoporosis. |
|
E.2.2 | Secondary objectives of the trial |
• Determine the effects of six months of treatment with BA058 Transdermal on lumbar spine BMD when compared with placebo.
• Determine the effects of six months of treatment with BA058 Transdermal on hip and forearm BMD when compared with placebo.
• Determine the effects of six months of treatment with BA058 Transdermal on serum markers of bone formation and resorption when compared with placebo.
• Determine the safety and tolerability of six months of dosing with BA058 Transdermal.
• Select a dose level of BA058 Transdermal for further clinical evaluation.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• The subject is a healthy ambulatory postmenopausal woman not older than 85 years of age with osteoporosis.
• Subject has been postmenopausal for at least 5 years.
• Subject has a BMD T-score ≤ -2.5 at the lumbar spine or hip (femoral neck) by dual energy x-ray absorptiometry (DXA).
- Subjects may also be included if they have a BMD T-score of ≤ 2.0 and a prior low-trauma forearm, humerus, vertebral, sacral, pelvic, hip, femoral, or tibial fracture within the past 5 years
- or who have an additional risk factor such as age 65 to 85 , or a strong maternal history of osteoporosis.
• Is in good general health as determined by medical history and physical examination (including vital signs)
• The subject has serum calcium (albumin-corrected), PTH (1-84), serum phosphorus and alkaline phosphatase values all within the normal range during the Screening Period.
• Has a serum 25-hydroxy vitamin D value >15 ng/mL (37.4 nmol/L) and within 3 times the upper normal range.
• Subject’s resting 12-lead electrocardiogram shows no clinically significant abnormality and a QTc ≤470˚msec (Bazett’s correction).
• Subject’s systolic blood pressure is ≥100 and ≤155 mmHg, diastolic blood pressure is ≥40 and ≤95 mmHg, and heart rate is ≥45 and ≤100 bpm (sitting or supine).
• Subject has no clinically significant abnormality of serum hemoglobin, hematocrit, WBC and platelets, or serum biochemistry: electrolytes, renal function, liver function and serum proteins.
• Subject has signed the written informed consent form. |
|
E.4 | Principal exclusion criteria |
• Abnormalities of the lumbar spine that would prohibit assessment of spinal BMD.
• Unevaluable hip BMD or have undergone bilateral hip replacement
• History of bone disorders (e.g., Paget’s disease).
• Chronic radiation therapy other than radioiodine.
• History of chronic or recurrent disease or medical condition that would interfere with the interpretation of study data or compromise the safety of the subject.
• Significantly impaired renal function (serum creatinine >177 µmol/L or >2.0 mg/dL).
• History of any cancer within the past 5 years.
• History of osteosarcoma.
• History of nephrolithiasis or urolithiasis within the past 5 years.
• Decrease of 20 mmHg or more in systolic blood pressure or 10 mmHg or more in diastolic blood pressure from supine to standing and/or any symptomatic hypotension at screening
• Positive for Hepatitis B, Hepatitis C, HIV-1 or HIV-2.
• Known hypersensitivity to any of the test materials or related compounds.
• Prior treatment with PTH or PTHrP drugs.
• Prior treatment with bisphosphonates or strontium in the past five years, or prior treatment with gallium nitrate, or with a bone-acting investigational agent at any time.
• Prior treatment with denosumab, calcitonin, SERMs, tibolone, or anabolic steroids in the past 12 months.
• Treatments with anticonvulsants that affect vitamin D metabolism or with heparin within the 6 months prior.
• Daily treatment with oral, intranasal or inhaled corticosteroids above the equivalent of 5 mg oral cortisone per day within the 12 months prior.
• Exposure to general anesthesia within the four weeks prior.
• Exposure to an investigational drug within the 12 months prior.
• Abnormal nutritional status, vitamin D intake of ≥4,000 IU/day or vitamin A intake of ≥10,000 IU/day.
• Known to abuse alcohol or use illegal drugs within 12 months prior. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Changes in levels of PINP, PICP, BSAP, osteocalcin and CTXI
• Safety analyses will include the incidence and severity of adverse events by treatment, dose and cumulative dose and pathological changes in hematology, chemistry and urinalysis data
• Optimal Dose Selection |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
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 | 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 | 5 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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 |
Czech Republic |
Denmark |
Estonia |
Hong Kong |
Lithuania |
Poland |
Romania |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |