Male Osteoporosis
Conditions
Keywords
male osteoporosis, osteoporosis, bisphonates, bone
Brief summary
Male osteoporosis is a common and important clinical problem, associated with significant morbidity, mortality and societal expense. Approximately 10% of men =65 years of age are osteoporotic. The proposed study will evaluate efficacy and safety of oral ibandronate given 150 mg once-monthly for 12 months versus placebo in men with primary osteoporosis. Less frequent, once monthly, dosing is expected to improve patient's treatment adherence compared to a weekly dosing regimen.
Interventions
DRUGIbandronate
Ibandronate orally (tablet) at a dose of 150 mg once per month
DRUGplacebo
Placebo orally (tablet) at a dose of 150 mg once per month
Sponsors
GlaxoSmithKline
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ambulatory men at least 30 years old at screening, who are diagnosed with primary, idiopathic or hypogonadal osteoporosis according to the following criteria: Femoral neck (FN) BMD T-score \< -2.0 and LS BMD T-score \< -1.0 OR LS BMD T-score \< -2.0 and FN BMD T-score \< -1.0 and BMD T-score \> 4.0 at any site * Subjects who, in the opinion of the investigator, are willing and able to comply with the protocol requirements * Subjects who have signed an informed consent
Exclusion criteria
* Significant medical conditions or laboratory abnormalities, which in the opinion of the investigator may preclude the patient's ability to complete the study * Malignant disease diagnosed within the previous 5 years (except resected basal cell cancer) * Disease/disorder known to influence bone metabolism or cause of secondary osteoporosis e.g., chronic gastrointestinal or liver disease, renal disease, chronic alcoholism, malabsorption syndrome * Hypersensitivity to any component of ibandronate * Inability to stand or sit in an upright position for at least 60 minutes * Inability to swallow a tablet without breaking it * Vitamin D deficiency (serum 25-OH vitamin D \<20ng/mL (equivalent to 50nmol/L) at screening * Any prevalent osteoporotic vertebral fracture identified by total spine x-ray (Total spine x-ray consists of lateral and PA films of the thoracic & lumbar spine) * Subjects who are receiving testosterone supplementation for \< 2 years (if applicable) (Patients who are identified with clinical signs of hypogonadism at screening and are started on testosterone supplementation will be excluded from participation.) * Contraindications to calcium or vitamin D therapy * Administration of any investigational drug within 30 days preceding the first dose of the study drug * Previous treatment with an oral bisphosphonate within the last six months, OR more than one month of cumulative treatment within the last year, OR more than three months of cumulative treatment within the last two years AND/OR treatment with intravenous bisphosphonate within one year. * Treatment with PTH or similar anabolic agent for osteoporosis within the last two years * Treatment with other drugs affecting bone metabolism within the last six months prior to Screening including: * Chronic systemic glucocorticoid treatment except for topical treatment at a frequency of up to twice per week * Calcineurin inhibitors \[e.g., cyclosporine, tacrolimus\] or methotrexate * Testosterone therapy (unless stabilized on medications \> 2 years) * Calcitonin * Fluoride (dose greater than 10mg/day) or strontium for osteoporosis within the last 12 months, or past treatment for more than a total of 2 years * Selective estrogen receptor modulators (SERMS) such as raloxifene, toremifene, tamoxifen, arzoxifene and lasofoxifene * Anabolic steroids and other androgens, such as dehydroepiandrosterone (DHEA) or its sulphated form (DHEAs) * Active vitamin D analogs/metabolites such as1,25-dihydroxy vitamin D (calcitriol) or 1-alpha-hydroxy vitamin D3 (1 - alpha hydroxycholecalciferol) * Gonadotropin releasing antagonists (lupron) * ALT \> twice upper limit of normal range of central laboratory * Hypercalcemia or uncorrected hypocalcemia: Serum total Ca 2+ \> 10.5mg/dl or \< 8.0 mg/dL (equivalent to 2.6 and 2.0 mmol/L) * GFR \< 30 ml/min as determined by estimated creatinine clearance (CLcr) calculated by the Cockcroft-Gault equation: CLcr = (140-age) \* ABW X 0.85 72\*Scr where : CLcr - estimated creatinine clearance Age - in years ABW - actual body weight at screening (kg) Scr - serum creatinine at screening (mg/dL) * History of major upper GI disease defined by: * Significant upper GI bleeding within the last year requiring hospitalization or transfusion * Recurrent peptic ulcer disease documented by radiographic or endoscopic means * Dyspepsia or gastroesophageal reflux that is uncontrolled by medication * Abnormalities of the esophagus that delay esophageal emptying, such as stricture, achalasia, or dysmotility * Active gastric/duodenal ulcers * Dyspepsia controlled by daily medication OR prior history of non-recurrent peptic ulcer disease are not considered exclusionary * WBC \< 2500/µL * Serum albumin \< 3.0g/dL * History of hyperthyroidism, hyperparathyroidism or osteomalacia within one year of study entry * Fewer than three (3) vertebrae in the range L1-L4 evaluable by DXA. Conditions which interfere with the BMD measurement include prevalent fracture, sequelae of orthopedic procedures (e.g., spinal fusion, metal implants, etc.), severe scoliosis and severe degenerative changes (e.g., osteophytes, sclerosis) * Bilateral hip replacement * Any restrictions, defined by site requirements for hrMRI procedure (for subset of hrMRI subjects)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change in BMD of the Lumbar Spine From Baseline to Month 12 | 12 months | BMD will be assessed using an analysis of covariance model (ANCOVA) with datea obtained from dual-Energy X-ray absorptiometry scans. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change in BMD of the Lumbar Spine From Baseline to Month 6 | 6 months | BMD will be assessed using an analysis of covariance model (ANCOVA) with datea obtained from dual-Energy X-ray absorptiometry scans. |
| Mean Percent Change in BMD of Proximal Femur Sites (Total Hip, Trochanter, Femoral Neck) From Baseline to Month 12 | 12 months | BMD will be assessed using an analysis of covariance model (ANCOVA) with datea obtained from dual-Energy X-ray absorptiometry scans. |
| Mean Percent Change in BMD of Proximal Femur Sites (Total Hip, Trochanter, Femoral Neck) From Baseline to Month 6 | 6 months | BMD will be assessed using an analysis of covariance model (ANCOVA) with datea obtained from dual-Energy X-ray absorptiometry scans. |
| Responder Rate of Subjects Who Remained the Same or Had Any Improvement in BMD (>= Baseline) at 6 Months and 12 Months | 12 months | Responders are defined as participants who have BMD values \>= their baseline values at Months 6 and 12, and not any pre-defined percentage increase in BMD values of clinical significance. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo orally at a dose of 150 mg once a month for 12 months | 47 |
| Ibandronate Ibandronate orally at a dose of 150 mg once a month for 12 months | 85 |
| Total | 132 |
Baseline characteristics
| Characteristic | Total | Ibandronate | Placebo |
|---|---|---|---|
| Age Continuous | 64.3 years STANDARD_DEVIATION 10.98 | 63.9 years STANDARD_DEVIATION 11.2 | 65.0 years STANDARD_DEVIATION 10.63 |
| Age, Customized < 65 years | 65 participants | 42 participants | 23 participants |
| Age, Customized >= 65 years | 67 participants | 43 participants | 24 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 132 Participants | 85 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 47 | 27 / 86 |
| serious Total, serious adverse events | 6 / 47 | 7 / 86 |
Outcome results
Primary
Mean Percent Change in BMD of the Lumbar Spine From Baseline to Month 12
BMD will be assessed using an analysis of covariance model (ANCOVA) with datea obtained from dual-Energy X-ray absorptiometry scans.
Time frame: 12 months
Population: Intent-to-treat population. Includes participants with measurements at Baseline and Month 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Percent Change in BMD of the Lumbar Spine From Baseline to Month 12 | .94 percent | Standard Error 0.709 |
| Ibandronate | Mean Percent Change in BMD of the Lumbar Spine From Baseline to Month 12 | 3.52 percent | Standard Error 0.661 |
p-value: <0.00195% CI: [1.41, 3.76]ANCOVA
Secondary
Mean Percent Change in BMD of Proximal Femur Sites (Total Hip, Trochanter, Femoral Neck) From Baseline to Month 12
BMD will be assessed using an analysis of covariance model (ANCOVA) with datea obtained from dual-Energy X-ray absorptiometry scans.
Time frame: 12 months
Population: Intent-to-treat population. Includes patients with measurements at Baseline and Month 12.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Percent Change in BMD of Proximal Femur Sites (Total Hip, Trochanter, Femoral Neck) From Baseline to Month 12 | Total Hip | -0.31 percent | Standard Error 0.473 |
| Placebo | Mean Percent Change in BMD of Proximal Femur Sites (Total Hip, Trochanter, Femoral Neck) From Baseline to Month 12 | Femoral Neck | -0.23 percent | Standard Error 0.663 |
| Placebo | Mean Percent Change in BMD of Proximal Femur Sites (Total Hip, Trochanter, Femoral Neck) From Baseline to Month 12 | Trochanter | 0.43 percent | Standard Error 0.692 |
| Ibandronate | Mean Percent Change in BMD of Proximal Femur Sites (Total Hip, Trochanter, Femoral Neck) From Baseline to Month 12 | Total Hip | 1.82 percent | Standard Error 0.43 |
| Ibandronate | Mean Percent Change in BMD of Proximal Femur Sites (Total Hip, Trochanter, Femoral Neck) From Baseline to Month 12 | Femoral Neck | 1.21 percent | Standard Error 0.612 |
| Ibandronate | Mean Percent Change in BMD of Proximal Femur Sites (Total Hip, Trochanter, Femoral Neck) From Baseline to Month 12 | Trochanter | 2.15 percent | Standard Error 0.633 |
Comparison: Total Hip subgroupp-value: <0.00195% CI: [1.34, 2.92]ANCOVA
Comparison: Femoral Neckm subgroupp-value: 0.01295% CI: [0.32, 2.55]ANCOVA
Comparison: Trochanter subgroupp-value: 0.00495% CI: [0.56, 2.88]ANCOVA
Secondary
Mean Percent Change in BMD of Proximal Femur Sites (Total Hip, Trochanter, Femoral Neck) From Baseline to Month 6
BMD will be assessed using an analysis of covariance model (ANCOVA) with datea obtained from dual-Energy X-ray absorptiometry scans.
Time frame: 6 months
Population: Intent-to-treat population. Includes patients with measurements at Baseline and Month 6.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Percent Change in BMD of Proximal Femur Sites (Total Hip, Trochanter, Femoral Neck) From Baseline to Month 6 | Trochanter | 0.55 percent | Standard Error 0.677 |
| Placebo | Mean Percent Change in BMD of Proximal Femur Sites (Total Hip, Trochanter, Femoral Neck) From Baseline to Month 6 | Total Hip | -0.48 percent | Standard Error 0.386 |
| Placebo | Mean Percent Change in BMD of Proximal Femur Sites (Total Hip, Trochanter, Femoral Neck) From Baseline to Month 6 | Femoral Neck | -0.22 percent | Standard Error 0.63 |
| Ibandronate | Mean Percent Change in BMD of Proximal Femur Sites (Total Hip, Trochanter, Femoral Neck) From Baseline to Month 6 | Total Hip | 1.27 percent | Standard Error 0.349 |
| Ibandronate | Mean Percent Change in BMD of Proximal Femur Sites (Total Hip, Trochanter, Femoral Neck) From Baseline to Month 6 | Femoral Neck | 0.96 percent | Standard Error 0.58 |
| Ibandronate | Mean Percent Change in BMD of Proximal Femur Sites (Total Hip, Trochanter, Femoral Neck) From Baseline to Month 6 | Trochanter | 2.59 percent | Standard Error 0.616 |
Comparison: Total Hip subgroupp-value: <0.00195% CI: [1.11, 2.4]ANCOVA
Comparison: Femoral Neck subgroupp-value: 0.03195% CI: [0.11, 2.25]ANCOVA
Comparison: Trochanter subgroupp-value: 0.03195% CI: [0.11, 2.25]ANCOVA
Secondary
Mean Percent Change in BMD of the Lumbar Spine From Baseline to Month 6
BMD will be assessed using an analysis of covariance model (ANCOVA) with datea obtained from dual-Energy X-ray absorptiometry scans.
Time frame: 6 months
Population: Intent-to-treat population. Includes patients with measurements at Baseline and Month 6.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Percent Change in BMD of the Lumbar Spine From Baseline to Month 6 | 0.78 percent | Standard Error 0.649 |
| Ibandronate | Mean Percent Change in BMD of the Lumbar Spine From Baseline to Month 6 | 1.64 percent | Standard Error 0.604 |
p-value: 0.11895% CI: [-0.22, 1.94]ANCOVA
Secondary
Responder Rate of Subjects Who Remained the Same or Had Any Improvement in BMD (>= Baseline) at 6 Months and 12 Months
Responders are defined as participants who have BMD values \>= their baseline values at Months 6 and 12, and not any pre-defined percentage increase in BMD values of clinical significance.
Time frame: 12 months
Population: Intent-to-treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Responder Rate of Subjects Who Remained the Same or Had Any Improvement in BMD (>= Baseline) at 6 Months and 12 Months | Month 6: Total Hip | 14 participants |
| Placebo | Responder Rate of Subjects Who Remained the Same or Had Any Improvement in BMD (>= Baseline) at 6 Months and 12 Months | Month 12: Lumbar Spine | 33 participants |
| Placebo | Responder Rate of Subjects Who Remained the Same or Had Any Improvement in BMD (>= Baseline) at 6 Months and 12 Months | Month 12: Total Hip | 20 participants |
| Placebo | Responder Rate of Subjects Who Remained the Same or Had Any Improvement in BMD (>= Baseline) at 6 Months and 12 Months | Month 6: Lumbar Spine | 30 participants |
| Placebo | Responder Rate of Subjects Who Remained the Same or Had Any Improvement in BMD (>= Baseline) at 6 Months and 12 Months | Month 12: Lumbar Spine and Total Hip | 16 participants |
| Placebo | Responder Rate of Subjects Who Remained the Same or Had Any Improvement in BMD (>= Baseline) at 6 Months and 12 Months | Month 6: Lumbar Spine and Total Hip | 10 participants |
| Ibandronate | Responder Rate of Subjects Who Remained the Same or Had Any Improvement in BMD (>= Baseline) at 6 Months and 12 Months | Month 12: Lumbar Spine and Total Hip | 59 participants |
| Ibandronate | Responder Rate of Subjects Who Remained the Same or Had Any Improvement in BMD (>= Baseline) at 6 Months and 12 Months | Month 6: Lumbar Spine | 62 participants |
| Ibandronate | Responder Rate of Subjects Who Remained the Same or Had Any Improvement in BMD (>= Baseline) at 6 Months and 12 Months | Month 6: Total Hip | 57 participants |
| Ibandronate | Responder Rate of Subjects Who Remained the Same or Had Any Improvement in BMD (>= Baseline) at 6 Months and 12 Months | Month 6: Lumbar Spine and Total Hip | 46 participants |
| Ibandronate | Responder Rate of Subjects Who Remained the Same or Had Any Improvement in BMD (>= Baseline) at 6 Months and 12 Months | Month 12: Total Hip | 64 participants |
| Ibandronate | Responder Rate of Subjects Who Remained the Same or Had Any Improvement in BMD (>= Baseline) at 6 Months and 12 Months | Month 12: Lumbar Spine | 71 participants |
Comparison: Total Spine BMD at Month 6p-value: 0.36295% CI: [0.73, 1.13]Cochran-Mantel-Haenszel
Comparison: Total Spine BMD at Month 12p-value: 0.04495% CI: [0.72, 1.01]Cochran-Mantel-Haenszel
Comparison: Total Hip BMD at Month 6p-value: <0.00195% CI: [0.3, 0.72]Cochran-Mantel-Haenszel
Comparison: Total Hip BMD at Month 12p-value: <0.00195% CI: [0.41, 0.8]Cochran-Mantel-Haenszel
Comparison: Both Total Hip and Total Spine BMD at Month 6p-value: <0.00195% CI: [0.23, 0.72]Cochran-Mantel-Haenszel
Comparison: Both Total Hip and Total Spine BMDp-value: <0.00195% CI: [0.33, 0.75]Cochran-Mantel-Haenszel