| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Osteoporosis or Osteopenia |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10049088 |
| E.1.2 | Term | Osteopenia |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10031285 |
| E.1.2 | Term | Osteoporosis postmenopausal |
|
| 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 |
| The primary objective of this trial is to compare the percentage change in DXA BMD of the lumbar spine between baseline and 12 months following treatment with ONO-5334 or placebo. |
|
| E.2.2 | Secondary objectives of the trial |
The following secondary objectives of this trial will be assessed during initial 12-month data:
• To compare the effect of ONO-5334 or once weekly Alendronate (Fosamax Once Weekly®) versus placebo on DXA BMD and BMC (Lumbar spine, Total hip, Femoral neck and Trochanter) and biochemical markers of bone turnover from baseline during 12 month treatment.
• To compare the proportions of responders to ONO-5334 or Alendronate therapy at the end of 12 months treatment compared with placebo.
• To compare the safety and tolerability of ONO-5334 or Alendronate versus placebo.
• To compare compliance with treatment with ONO-5334 or Alendronate versus placebo.
• To compare the efficacy and safety of ONO-5334 versus Alendronate.
• To investigate the efficacy and safety of three different doses of ONO-5334 (50mg BID, 100mg QD, 300mg |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
INCLUSION CRITERIA FOR THE INITIAL 12-MONTH TREATMENT PHASE
1. Post menopausal women aged between 55 and 75 years old inclusive (55 ≤ age ≤ 75). Post menopausal is defined as more than 5 years after menopause and with Oestradiol and FSH levels consistent with menopause (FSH > 30IU/L, Oestradiol <92pmol/L),
2. Osteoporosis defined as a value of DXA BMD 2.5 standard deviations or more below the young adult mean (T-score ≤ -2.5) at the lumbar spine (L1 to L4) or total hip, OR, Osteopenia defined as a value of DXA BMD more than 1 standard deviation below the young adult mean, but less than 2.5 standard deviations below this value (T-score <-1 and >-2.5) at the lumbar spine (L1 to L4) or total hip.
3. Able and willing to give written informed consent.
INCLUSION CRITERIA FOR THE 12-MONTH EXTENDED TREATMENT PHASE
1. Patients who have completed the initial 12-month treatment phase of the study.
2. Patients who are able and willing to give written informed consent for the extended treatment phase. |
|
| E.4 | Principal exclusion criteria |
1. value of DXA BMD more than 3.5 standard deviation below the young adult mean, (T-score < -3.5) at the lumbar spine (L1 to L4) or total hip.
2. Osteoporosis patients (T-score ≤ -2.5) who have any vertebral fragility fracture between T4 and L4 inclusive.
3. Osteopenia pts. (T-score <-1 and >-2.5) who have no vertebral fragility fractures between T4 and L4 inclusive,
OR, Osteopenia pts.(T-score <-1 and >-2.5) who have two or more vertebral fragility fractures between T4 and L4 inclusive
4. History of any non-vertebral fragility fractures after age of 50.
5. Abnormalities of the lumbar spine or femoral neck or internal organs around them precluding the assessment of BMD. e.g.,
A) severe scoliosis.
B) two or more vertebral levels in L1, L2, L3, L4 that are not evaluable by DXA due to fracture, metal implants or other orthopaedic procedures etc.,
C) a previous fracture, severe deformity or metal pins, plates, prostheses, etc., affecting either femur.
D) severe osteoarthritis (oeteophytes, sclerosis, etc.) in L1, L2, L3, L4 or femoral neck
E) severe aortic calcification interfering with spinal BMD measurement.
6. Clinically relevant fractures 1 year prior to the Randomisation v.(Visit 1).
7. Secondary causes of osteoporosis. e.g.,
A) Endocrine disorders: thyrotoxicosis, primary hyperparathyroidism, Cushing’s syndrome
B) Rheumatologic conditions: RA, ankylosing spondylitis
C) Gastro-intestinal disorders: malabsorption partial gastrectomy
D) Malignancy: multiple myeloma, metatastic carcinoma
E) Drug treatment: systemic oral glucocorticoids, methotrexate, heparin, anti-convulsants
F) Genetic disorders:osteogenesis imperfecta
G) Nutritional deficiencies:osteomalacia or anorexia
H) Immobility
I) Other conditions: Diabetes(patients with IDDM, insulin treated or HbA1c ≥8.0%), hepatic impairment (defined by the exclusion criteria 8), alcohol intake (≥20 unit per week)
8. Disorders of bone and mineral metabolism. e.g.
A) Vitamin D deficiency (defined as serum 25 hydroxy vitamin D value < 10 ng/mL)
B) Hypocalcemia (defined as serum Calcium < 8.5 mg/dL)
C) Paget’s disease of bone
D) Controlled or uncontrolled hypo- or hyperthyroidism, hypo or hyperparathyroidism, hypo- or hypercalcemia
E) Osteomalacia, or osteogenesis imperfecta
9. Patients for whom once weekly Alendronate treatment is contraindicated.
10. Low bone turnover defined as urinary CTX-I below 200μg /mmolCr at the Screening visit.
11. History or presence of other significant disease, which in the opinion of the Investigator, might compromise the patient’s safety or the evaluation of the study results.
12. A history of drug or alcohol abuse (alcoholic patients who are recovered for at least 2 years will be allowed to enrol in this study).
13. History of malignancy within the past 5 years of the Screening v.
14. Impaired hepatic function defined as raised liver function tests (ASAT, ALAT, alkaline phosphatase) greater than 2.5 times upper limit of laboratory normal.
15. Impaired renal function defined as calculated creatinine clearance < 35mL/min based upon the value derived from the Cockcroft and Gault equation.
16. Any previous use of PTH and its derivatives, Strontium or Fluoride including ones in development before Screening visit.
17. Use of bisphosphonates in the 3 years preceding the Screening v.
18. Use of HRT, SERMs, Calcitonin, Anabolic steroids, Thiazides (>12mg/day hydrochlorothiazide or equivalent), Vitamin K (at doses > 200 μg/day) or any medication that may in the opinion of the Investigator have an effect on bone metabolism in the preceding 1 year of the Screening v.
19. Use of Systemic oral glucocorticoids, High daily dose of inhaled glucocorticoids, Methotrexate, Systemic heparin or Anti-convulsant in the preceding 1 year of the Screening visit.
20.Use of cytochrome P450 3A4 inhibitors or inducers specified in Section 10.5.3.2 in the preceding one week of the Randomisation v. (Visit 1).
21. Poor medication compliance: defined as taking <80% of the elemental calcium and vitamin D dose scheduled between the Screening v. and the Randomisation v. (Visit 1).
22. Usage of any investigational drug and/or participation in any clinical trial within 3 months of the Screening visit.
23. Patients previously received ONO-5334.
24. In the opinion of the Investigator, the patient may not be able to cooperate fully with the study staff, may have difficulty following some requirements, or is otherwise not qualified for the study.
EXCLUSION CRITERIA FOR THE 12-MONTH EXTENDED TREATMENT PHASE
1. 1. Patients for whom the Investigator has any safety concerns and judges it would not be in the best interest of the patient to continue with any of the study medications.*
2. Patients whom, in the opinion of the Investigator, may not be able to cooperate fully with the study requirements. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| To compare the percentage change in DXA BMD of the lumbar spine between baseline and 12 months following treatment with ONO-5334 or placebo |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Information not present in EudraCT |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| 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.8.3 |
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 | Information not present in EudraCT |
| E.8.5.1 | Number of sites anticipated in the EEA | 13 |
| 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 | Information not present in EudraCT |
| 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
| |
| 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 | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
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