Clinical trial NCT00397839: The Effect Of Oral Ibandronate In Male Osteoporosis
Official title: A Parallel, Placebo-controlled, Randomized (2:1) Double-blind Study of One Year Duration to Assess the Effect of Oral Ibandronate 150 mg Given Once-monthly Versus Placebo on LS BMD in Men With Osteoporosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Male Osteoporosis
Keywords: male osteoporosis
osteoporosis
bisphonates
bone
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2006-11-10
Enrollment: 135
Sex: MALE
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Mean Percent Change in BMD of the Lumbar Spine From Baseline to Month 12
timeFrame: 12 months
Secondary outcomes:
measure: Mean Percent Change in BMD of the Lumbar Spine From Baseline to Month 6
timeFrame: 6 months
measure: Mean Percent Change in BMD of Proximal Femur Sites (Total Hip, Trochanter, Femoral Neck) From Baseline to Month 12
timeFrame: 12 months
measure: Mean Percent Change in BMD of Proximal Femur Sites (Total Hip, Trochanter, Femoral Neck) From Baseline to Month 6
timeFrame: 6 months
measure: Responder Rate of Subjects Who Remained the Same or Had Any Improvement in BMD (>= Baseline) at 6 Months and 12 Months
timeFrame: 12 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Tucson
country: United States
facility: GSK Investigational Site
state: Arizona
city: Beverly Hills
country: United States
facility: GSK Investigational Site
state: California
city: Greenbrae
country: United States
facility: GSK Investigational Site
state: California
city: Oakland
country: United States
facility: GSK Investigational Site
state: California
city: Palm Desert
country: United States
facility: GSK Investigational Site
state: California
city: Walnut Creek
country: United States
facility: GSK Investigational Site
state: California
city: Longmont
country: United States
facility: GSK Investigational Site
state: Colorado
city: Clearwater
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Palm Harbor
country: United States
facility: GSK Investigational Site
state: Florida
city: West Palm Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Decatur
country: United States
facility: GSK Investigational Site
state: Georgia
city: Gainsville
country: United States
facility: GSK Investigational Site
state: Georgia
city: Champaign
country: United States
facility: GSK Investigational Site
state: Illinois
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Peoria
country: United States
facility: GSK Investigational Site
state: Illinois
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Kansas
city: Louisville
country: United States
facility: GSK Investigational Site
state: Kentucky
city: South Portland
country: United States
facility: GSK Investigational Site
state: Maine
city: Bathesda
country: United States
facility: GSK Investigational Site
state: Maryland
city: Wheaton
country: United States
facility: GSK Investigational Site
state: Maryland
city: Woodbury
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Springfield
country: United States
facility: GSK Investigational Site
state: Missouri
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
city: Asheville
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Tulsa
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Portland
country: United States
facility: GSK Investigational Site
state: Oregon
city: Duncansville
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Providence
country: United States
facility: GSK Investigational Site
state: Rhode Island
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Richmond
country: United States
facility: GSK Investigational Site
state: Virginia
city: Salem
country: United States
facility: GSK Investigational Site
state: Virginia
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Beckley
country: United States
facility: GSK Investigational Site
state: West Virginia
city: Madison
country: United States
facility: GSK Investigational Site
state: Wisconsin
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials, MD
role: STUDY_DIRECTOR
References: