E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10031282 |
E.1.2 | Term | Osteoporosis |
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 |
The primary objective is to evaluate the effect of denosumab 60 mg Q6 months compared with placebo on lumbar spine BMD at 12 months in men with low BMD. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate the effects of denosumab in men with low BMD compared to placebo on
• BMD at proximal femur (total hip, hip trochanter, femoral neck) and distal radius at 12 months
• CTX at Day 15
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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 |
Transiliac Bone Biopsy Sub-study, 22 Jun 09
A target of approximately 20 subjects enrolled at selected study sites will be requested to undergo a transiliac bone biopsy within 30 days prior to the month 12 visit in order to evaluate the effect of denosumab on bone histology and histomorphometry. |
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E.3 | Principal inclusion criteria |
BMD values (g/cm2) assessed by the local site at either the lumbar spine OR femoral neck that occur within the following ranges, based on the particular scanner that is used:
GE Lunar Hologic
Lumbar spine 0.800 ≤ BMD ≤ 0.980 0.706 ≤ BMD ≤ 0.871
Femoral neck 0.573 ≤ BMD ≤ 0.808 0.454 ≤ BMD ≤ 0.658
OR
For subjects with a history of a major osteoporotic fracture (clinical vertebral, hip, humerus and distal radius fractures) occurring more than 6 months prior to screening, BMD values (g/cm2) assessed by the local site, at either the lumbar spine OR femoral neck that occur within the following ranges, based on the particular scanner that is used:
GE Lunar Hologic
Lumbar spine 0.800 ≤ BMD ≤ 1.100 0.706 ≤ BMD ≤ 0.981
Femoral neck 0.573 ≤ BMD ≤ 0.965 0.454 ≤ BMD ≤ 0.794
At least 2 lumbar vertebrae, at least 1 hip and at least one forearm must be evaluable by DXA.
Ambulatory males 30 to 85 years of age inclusive at the start of screening.
Provide the appropriate written informed consent before any study-specific procedure.
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E.4 | Principal exclusion criteria |
BMD values (g/cm2) in subjects with or without a history of major osteoporotic fractures, based on the particular scanner that is used:
GE Lunar Hologic
Lumbar spine BMD < 0.800 BMD < 0.706
Femoral neck BMD < 0.573 BMD < 0.454
Any disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.
Any severe or more than 1 moderate vertebral fractures on screening spinal x-ray
Any vertebral fracture diagnosed within the 6 months prior to screening
Any clinical fracture within the last 6 months prior to screening
For males with a partner of childbearing potential: Subject refuses to use 2 highly effective methods of contraception for the duration of the study and for 10 months after the last dose of study medication.
For males with a partner who is pregnant: Subject refuses to use a condom for the duration of the study and for 10 months after the last dose of study medication.
Previous participation in clinical trials with denosumab or administration of commercial denosumab.
Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s).
Vitamin D deficiency [25(OH) vitamin D level < 20 ng/mL (< 49.9 nmol/L)]. Vitamin D replenishment will be permitted and subjects may be re-screened; see Section 7.
Hyper- or hypothyroidism; however, stable subjects, in the investigator’s opinion, on thyroid hormone replacement therapy are allowed.
Hyper- or hypoparathyroidism. iPTH values outside of the reference range as determined by the central laboratory
Elevated transaminases. Serum aspartate aminotransferase; serum glutamate-oxaloacetic transaminase > 2.5 x upper limit of normal. Serum alanine aminotransferase; serum glutamate-pyruvate transaminase > 2.5 x upper limit of normal (both as determined by the central laboratory).
Significantly impaired renal function as determined by a derived glomerular filtration rate (using the Modification of Diet in Renal Disease formula) of ≤ 30 mL/min/1.73 m2 calculated by the central laboratory.
Hypo- or hypercalcemia based on the central laboratory reference ranges for albumin-adjusted serum calcium.
Known to have tested positive for human immunodeficiency virus, hepatitis C virus, hepatitis B surface antigen or cirrhosis of the liver.
Malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma) within the last 5 years.
Any metabolic bone disease, eg osteomalacia, osteogenesis imperfecta, rheumatoid arthritis, Paget’s disease, Cushing’s disease or, hyperprolactinemia which may interfere with the interpretation of the findings OR evidence of malabsorption syndromes which might interfere with absorption of vitamin D.
Received any solid organ or bone marrow transplant or is on chronic immunosuppression for any reason.
Any laboratory abnormality, which in the opinion of the investigator or Amgen, will prevent the subject from completing the study or interfere with the interpretation of the study results.
Administration of intravenous bisphosphonate, or fluoride (except for dental treatment) or strontium ranelate.
Oral bisphosphonate treatment:
• ≥ 3 months cumulatively in the past 2 years, OR
• ≥ 1 month in the past year, OR
• Any use during the 3-month period prior to randomization
Administration of any of the following treatments 3 months prior to screening:
• Anabolic steroids or testosterone
• Glucocorticosteroids (≥ 5 mg prednisone equivalent per day for more than 10 days or a total cumulative dose of ≥ 50 mg)
• Calcitonin
• Calcitriol or vitamin D derivatives [vitamin D contained in supplements or multivitamins is allowed]
• Other bone active drugs including anti-convulsives (except benzodiazepines) and heparin
• Chronic systemic ketoconazole, ACTH (adrenocorticotrophic hormone), cinacalcet, aluminum, lithium, protease inhibitors, methotrexate, gonadotropin-releasing hormone agonists.
• Androgen deprivation therapy
Known sensitivity to mammalian cell derived drug products.
Known intolerance to calcium or vitamin D supplements.
Height, weight or girth which may preclude accurate DXA measurements.
Bilateral hip replacements
Any physical or psychiatric disorder which, in the opinion of the investigator or Amgen, will prevent the subject from completing the study or interfere with the interpretation of the study results.
Evidence of alcohol or substance-abuse within the last 12 months which the investigator believes would interfere with understanding of or completion of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the percent change from baseline in the lumbar spine BMD |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Percent change from baseline in BMD of the total hip, femoral neck, hip trocanter and distal radius - Percent change from baseline in CTX |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Percent change from baseline in BMD of the total hip, femoral neck, hip trocanter and distal radius at Month 12
- Percent change from baseline in CTX at Day 15 |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 20 |
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 |
European Union |
Canada |
United States |
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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
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End of study is defined as the date the last on study subject completes the final study visit. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |