The objective of this study is to investigate if use of ONO-5334 has a more positive effect on bone density and biochemical markers of bone turnover than Alendronate (a bisphosphonate) and placebo.
ID
Source
Brief title
Condition
- Bone disorders (excl congenital and fractures)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this clinical study is to compare the percentual
change in bone density of the lumbar spine between baseline and 12 months
following treatment with ONO-5334 or placebo. The objective of the extension
study is to investigate the efficacy of ONO-5334 over a longer period.
Secondary outcome
- To compare the effect of ONO-5334 or once weekly Alendronate versus placebo
on DXA BMD and BMC and biochemical markers of bone turnover.
- To compare the proportions of responders to ONO-5334 or Alendronate therapy
versus 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.
Background summary
Osteoporosis is a systemic disease characterized by a progressive decrease in
bone mass due to an imbalance between bone resorption (involving the protein
cathepsin K) and bone formation. Bisphosphonates are commonly used for
prevention and treatment of osteoporosis, but inhibit not only bone resorption,
but also bone formation. If a cathepsin K inhibitor that inhibits bone
resorption without affecting bone formation would be available, there is a
possibility this would strongly improve bone mass and bone strength.
ONO-5334 is a potent and selective cathepsin K inhibitor and has shown
suppressive effects on bone resorption, and may have a clinical role in
treatment of osteoporosis. The hypothesis of this study is that one or more of
the investigational doses of ONO-5334 will result in a relative increase of
bone density in the lumbar spine of at least 4% compared with baseline levels.
Study objective
The objective of this study is to investigate if use of ONO-5334 has a more
positive effect on bone density and biochemical markers of bone turnover than
Alendronate (a bisphosphonate) and placebo.
Study design
This is a double blind, placebo controlled trial, in which patients will
receive one out of three dosages of ONO-5334, placebo or Alendronate once
weekly after randomisation, for a treatment period of 12 months. During the
trial, bone density will be assessed using X-rays of the lumbar spine, DXA BMD
and QCT BMD. Additionally, biochemical bone turnover markers will be assessed
from blood and urine samples. The extension study reflects an extension of the
study with 12 months, to determine long term efficacy of ONO-5334.
Intervention
During the treatment period, the subjects will receive:
either 50 mg ONO-5334, twice daily,
either 100 mg ONO-5334 once daily,
either 300 mg ONO-5334 once daily,
either a weekly dose of Alendronate (Fosamax 70mg Once Weekly)
or placebo, and additionally (for all groups) daily 1000mg Calcium and 800IU
Vitamin D as a supplement.
Study burden and risks
- The patients will need to keep a weekly telephone diary
- Patients need to have fasted overnight before the second screening visit and
all following study visits (except visits 7 and 9)
- Physical examination at screening, visits 4, 6, 10, Follow Up 1
- ECG at screening, visits 3, 4, 5, 6, 8, 10, Follow Up 1
- Spine X-ray at screening, visit 6, and visit 10
- CT scan of spine and femur at visit 1, 6 and 10 (optional)
- DXA BMD at screening, and visits 3,4, 6, 8, 10
- Drawing of blood samples at screening and all treatment visits except 7 and 9
- Urine sample at screening and all treatment visits except 7 and 9
- Measuring blood pressure and heart rate at screening and visits 3, 4, 5, 6,
8, 10, Follow Up 1
11th Floor, Marble Arch Tower, 55 Bryanston Street
W1H 7AA, London
United Kingdom
11th Floor, Marble Arch Tower, 55 Bryanston Street
W1H 7AA, London
United Kingdom
Listed location countries
Age
Inclusion criteria
- Post-menopausal women aged between 55 and 75 years old
- Osteoporosis defined as a value of DXA BMD 2.5 standard deviations or more below the young adult mean at the lumbar spine or total hip in the absence of any fragility fractures OR
- Osteopenia defined as a value of DXA BMD more than 1 standard deviation below the young adult mean, but less that 2.5 standard deviations below this value at the lumbar spine or total hip with the presence of one or more fragility fractures
- Written informed consent
Exclusion criteria
- Patients with a value of DXA BMD more than 3.5 standard deviation below the young adult mean at the lumbar spine or total hip,
- Patients who have abnormalities of the lumbar spine or femoral neck or internal organs around them precluding the assessment of BMD,
- Patients who have experienced clinical fractures one year prior to the Randomisation visit (visit 1)
- Patients who have secondary causes of osteoporosis
- Patients who have other disorders of bone and mineral metabolism
- Patients for whom once weekly Alendronate treatment is contraindicated
- Patients with a low bone turnover defined as urinary CTX-I below 200 microgramme/mmolCr at the Screening visit
- Patients who have 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
- A history of drug or alcohol abuse
- Patients who have history of malignancy within the past 5 years of the Screening visit.
- Patients with impaired hepatic function
- Patients with impaired renal function
- Any previous use of PTH and its derivatives, Strontium or Fluoride including ones in development before screening visit
- Use of bisphosphonates in the three years preceding screening visit
- Use of HRT, SERMs, Calcitonin, Anabolic Steroid, Thiazides, Vitamin K or any medication that may in the opinion of the investigator have an effect on bone metabolism in the preceding one year or the screening visit
- Use of Antacids, Systemic oral glucocorticiods, high daily dose of inhaled glucocorticoids, Methotrexate, Systemic heparin or Anti-convulsant in the preceding one year of the Screening visit
- Poor medication compliance (<80%)
Patients who have sed any investigational drug and/or participated in any clinical trial within 3 months of the Screening visit
- Patients who have previously received ONO-5334
- In the opinion of the invastigator, 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-002417-39-NL |
| CCMO | NL18017.003.07 |