Official Title: “A Randomized, Double-Blind, Placebo-Controlled, Prospective, Cross-Over Phase II Clinical Trial to Determine the Safety and Efficacy of Alendronate (Fosamax) in Juvenile Osteoporosis (IND#60,017)”

We have previously evaluated the safety and efficacy of Fosamax in 10 patients with juvenile osteoporosis during a 12-month clinical trial. We have documented that Fosamax improved BMD of the spine and hip without any major side effects. There were no additional fractures during therapy. The present study is designed to further evaluate the safety and efficacy of Fosamax in 20 children with juvenile osteoporosis using a double-blind, randomized, placebo-controlled, cross-over protocol.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Crossover Assignment, Safety/Efficacy Study

Study Primary Completion Date: April 2008

Osteoporosis is an uncommon disease in children and early adolescents. Patients have a low bone mineral density, develop fractures with minimal or no trauma, and frequently have a negative family history. The disease results from either diminished bone formation or increased bone removal (resorption).

No specific drug therapy has been recommended for juvenile osteoporosis. Alendronate (Fosamax) is effective in inhibiting bone resorption, increasing BMD and reducing fractures in adults with postmenopausal osteoporosis, but have not become established therapies in children. In the present study, we plan to evaluate the safety and efficacy of Fosamax in 20 patients with juvenile osteoporosis in a two-year period. This is a randomized, double-blind, placebo-controlled protocol. In the year-1, 10 patients will be assigned to receive Fosamax and 10 patients placebo. In the year-2, patients will be crossed over to the second arm of the study. Those who received Fosamax in the year-1, will receive placebo in the second year and vice versa. The patients will have 5 visits, the initial screening visit followed by 4 post therapy visits in a six-month interval. Measurements include DEXA of spine and hip, urinalysis and blood work.

Intervention(s) in this Clinical Trial

• Drug: Alendronate
  • dosage form:tablet dosage: 35mg (<40kg body weight) or 70mg (>40kg body weight) at the time of start. frequency: weekly duration:12 months

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: 2
  • Crossover study. Year-1, 10 participants will take study medication and other 10 participants will take placebo. Year-2, they will crossover to the second arm of the study. Those who took study medication in year-1, will take placebo in the year-2, and those 10 participants who took placebo in the year-1, will take study medications in the year-2.
• Placebo Comparator: 1
  • year-1, 10 participants will take Alendronate (study medication). and another 10 participants will take placebo. In year-2 they will crossover.

Primary Measures

• Bone mineral density (BMD) of the lumbar spine at 12 and 24 months at 12 months
  • Time Frame: 20-30 min
    Safety Issue?: Yes

Secondary Measures

• Bone Mineral Density of Hip at 12 and 24 months. Fracture rate before and during therapy. Biochemical markers to determine whether the primary effect of therapy is on bone formation or resorption.
  • Time Frame: 20-30 min (BMD); 4 hours (biochemical assays)
    Safety Issue?: Yes

Eligibility Criteria:

• 5-15 yrs of age
• Weighing 20 kg and more
• History of multiple fractures
• Tanner stage II or less
• Osteoporosis by DEXA (normative data available for these age group will be used to calculate Z scores.

Inclusion Criteria:

• Male and female children with a history of one or more atraumatic fractures, or evidence of one or more compression fractures on radiographs of the spine (reduction of >20 percent).
• Bone Mineral Density (BMD) determined by DEXA (QDR4500) to confirm osteoporosis at a Z score greater than 2 SD (standard deviations) below the normal mean for age (Z score <
• 2 SD).
• Parental consent (and patient assent after age 12 years) to participate in the study.
• Sexual development at: Tanner stage II or less (Prepubertal stage).
• Weight = 20 kg and more.

Exclusion Criteria:

• History of severe gastritis or reflux.
• Abnormalities of the esophagus that delay emptying, such as strictures or achalasia
• Marked kyphoscoliosis or the inability to sit or stand for at least 30 minutes
• Hypersensitivity to bisphosphonates
• Uncorrected hypocalcemia
• History of gastric or duodenal ulcers
• Renal dysfunction as indicated by serum Cr >1.5 mg/dl.
• Liver dysfunction as indicated by serum SGPT > 2 times the upper limit for age or serum total bilirubin > 2.0 mg/dl.
• Diagnosis of osteogenesis imperfecta, a family history of osteogenesis imperfecta, blue sclerae or deafness.
• Diagnosis of active rickets or osteomalacia or serum bone alkaline phosphatase 2 times greater than normal for age.
• Pregnancy
• Anorexia Nervosa

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 5 Years

Maximum Age for this Clinical Trial: 15 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: FDA Office of Orphan Products Development

Overall Clinical Trial Officials and Contacts

Lyndon L Key, M.D. Principal Investigator Medical University of South Carolina  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00259857

Study ID Number: 5 R01 FD001847-05

ClinicalTrials.gov Identifier: NCT00259857

Health Authority: United States: Food and Drug Administration

Medical University of South Carolina, Children's Hospital