Denosumab in Primary Hyperparathyroidism

Summary

Primary hyperparathyroidism (PHPT), a disease characterized by excess parathyroid hormone (PTH) and high blood calcium, is one of the most common endocrine disorders. PHPT is seen most often in postmenopausal women. Many patients with PHPT have low bone mineral density (BMD) when bone mass is measured by dual energy x-ray absorptiometry (DXA), primarily at the forearm. There is currently no effective medical therapy which increases bone density at the forearm in patients with PHPT.

PTH both builds and breaks down bone, and the pathways by which PTH mediates these actions are beginning to be identified. Prior research suggests that RANKL, a molecule important in bone metabolism, responds to PTH, and that if the RANKL is inactivated, PTH is shifted towards building bone. The investigators will study the effect of Denosumab, a therapeutic agent that binds to and inactivates RANKL, in 28 postmenopausal women with PHPT. Our hypothesis is that Denosumab will increase bone mineral density in primary hyperparathyroidism.

The study will last two years, and subjects will be randomly assigned to receive either placebo or Denosumab for the first year of the study. In the second year, all subjects will receive Denosumab. Denosumab (60 mg) or placebo will be given every 6 months by an injection just under the skin. Study procedures performed will include bone mineral density tests by DXA, high-resolution peripheral quantitative computed tomography (HR-pQCT) scans, and assessments of biochemical markers of calcium metabolism and bone turnover using both blood and urine samples of subjects with PHPT.

Conditions

• Primary Hyperparathyroidism

Interventions

DRUG

Denosumab

The dose of denosumab is 60 mg every 6 months by subcutaneous injection. The 52 subjects will be randomly allocated (2:1) into treatment and placebo arms with the placebo group receiving a subcutaneous injection of vehicle in year 1. In year 2, those who were allocated to the study drug in year 1 will continue in year 2. Those who were allocated to placebo in year 1 will be crossed over to study drug in year 2. Group # 1: Receive active drug for year 1 and year 2 of the study Group #2: Receive placebo for year 1 and active drug for year 2 of the study

OTHER

Placebo

The dose of denosumab is 60 mg every 6 months by subcutaneous injection. The placebo group will receive vehicle injections at the same time interval. The 52 subjects will be randomly allocated (2:1) into treatment and placebo arms with the placebo group receiving a subcutaneous injection of vehicle in year 1. In year 2, those who were allocated to the study drug in year 1 will continue in year 2. Those who were allocated to placebo in year 1 will be crossed over to study drug in year 2. Group # 1: Receive active drug for year 1 and year 2 of the study Group #2: Receive placebo for year 1 and active drug for year 2 of the study

Sponsors & Collaborators

• National Institutes of Health (NIH)

  collaborator NIH

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  collaborator NIH

• Amgen

  collaborator INDUSTRY

• Columbia University

  lead OTHER

Principal Investigators

• John P Bilezikian, MD · Columbia University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

40 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-01-31

Primary Completion

2014-10-31

Completion

2014-10-31

FDA Drug

Yes

Countries

• United States

Study Locations