Post-menopausal Osteopaenia MedDRA version: 16.1 Level: PT Classification code 10049088 Term: Osteopenia System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent prior to any study specific procedures. 2. Aged >50 and post-menopausal based on amenorrhoea for >12 months. 3. Documented presence of osteopaenia (bone density T-score at lumbar spine or hip of less than -1 and greater than -2.5 by Dual-energy X-ray Absorptiometry (DXA) criteria). 4. Placebo treatment for the duration of the study must not be considered detrimental to the study subject. 5. Must be able to understand the patient information sheet and consent form and comply with study requirements. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: Bone Related Exclusion Criteria: 1 Clinical or biochemical evidence of secondary causes of bone loss 2. 25-OH vitamin D level twice upper limit normal on 2 consecutive measurements. 6. Liver transaminases > upper limit normal. 7. Alkaline phosphatase > upper limit normal. 8. Bilirubin (total) > upper limit normal. 9. User of recreational or illicit drugs (including marijuana) or has had a recent history (within the last year) of drug or alcohol abuse or dependence. 10. Uncontrolled systemic hypertension (BP >150/90); on 3 successive measurements on the morning of the screening visit. 11. Systemic (including vaginal/rectal) or inhaled glucocorticoid treatment at the time of the screening visit. 12. Probenicid therapy at the time of the screening visit. 13. Any screening laboratory abnormality that, in the investigator’s judgement, is considered to be clinically significant 14. History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results of the subject’s ability to participate in the study. Specifically, a diagnosis of any inflammatory disorder that might reasonably need treatment with glucocorticoids during the course of the study. 15. History of any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs. 16. Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IP as judged by the investigator. 17. Hypersensitivity or intolerance to 11ß-HSD1 antagonists or to AZD4017. 18. Involvement in the planning and/or conduct of the study 19. Participation in any other clinical study within 1 month prior to the screening visit. 20. Previous randomisation for treatment in the present study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Principal objective To examine the effect of AZD4017, ie inhibition of the enzyme 11b hydroxysteroid dehydrogenase type 1, on the levels of biochemical markers of bone formation and resorption, in women with post-menopausal osteopaenia. Bone turnover markers are substances detectable in blood tests that reflect how much bone is being removed (resorbed) by cells called osteoclasts, and how much is being formed by cells called osteoblasts. ;Secondary Objective: Secondary objectives 1. To examine the change over time in bone markers to provide information relating to remodeling imbalance. This means seeing if blocking the 11bHSD1 enzyme changes the amount that bone is formed and resorbed over the different timepoints while the subject is taking the medication, over the 3 months of the study. 2. To examine whether the changes in bone turnover markers correlate with the baseline or the change in the urinary [THF+alloTHF]/THE ratio (a marker of systemic 11b-HSD1 activity). We can measure the activity of the 11b HSD1 enzyme using a ratio of steroid breakdown products in the urine. By measuring this steroid ratio at the beginning of, and during the study, and seeing if it relates to the bone marker changes, we can assess whether the drug works in the way that we think it does, and whether patients who would benefit the most from the drug can be picked out early. 3. To examine the reversibility of 11b-HSD1 inhibitor on markers of bone f;Primary end point(s): Change in the bone formation marker serum osteocalcin between baseline and after 90 days treatment with AZD4017;Timepoint(s) of evaluation of this end point: Main evaluation = 0 compared to 90 days, will also compare with 180 days (3 months after discontinuation of AZD4017). Measurements will be taken at 7, 30 and 60 days while on treatment, for a dynamic evaluation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Outcome Variables: • The secondary endpoint for the study is the change in bone resorption marker (serum bCTx) between baseline and after 3 months treatment with AZD4017. • Further analyses: the change in bone density between baseline, 90 and 180 days. the change in remodeling ‘balance’ to see if increased formation is associated with reduced resorption. the change in muscle strength between baseline and 90 days. ;Timepoint(s) of evaluation of this end point: Main evaluation = 0 compared to 90 days, will also compare with 180 days (3 months after discontinuation of AZD4017). | — |
Countries
United Kingdom
Contacts
Public ContactCrowley
University of Birmingham
Outcome results
None listed