NCT00172081

TOP: Recombinant Human Parathyroid Hormone (ALX1-11) on Fracture Incidence in Women With Postmenopausal Osteoporosis

An 18-Month Double-Blind, Placebo-Controlled, Phase III, Trial With a 12-Month Interim Analysis of the Effect of Recombinant Human Parathyroid Hormone (ALX1-11) on Fracture Incidence in Women With Postmenopausal Osteoporosis

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 2,532 (actual)
• Sponsor: Shire · Industry
• Sex: Female
• Age: 45 Years
• Healthy volunteers: Not accepted

Summary

This is an 18-month, double-blind, placebo-controlled, Phase III trial with a 12-month interim analysis of the effect of ALX1-11, recombinant human parathyroid hormone (1-84) (rhPTH \[1-84\]), on fracture incidence in women with postmenopausal osteoporosis, the TOP study.

Detailed description

Parathyroid hormone (PTH), a polypeptide consisting of 84 amino acids that is synthesized and secreted by the parathyroid glands, is a principal regulator of calcium homeostasis through concerted action on kidney, intestine and bone. Parathyroid hormone exerts its action on bone to release calcium into the extracellular fluid as a process of bone remodeling and also to maintain the serum calcium concentration, but the exact mechanisms are not fully understood. In some circumstances, PTH may exert an anabolic action on bone and can stimulate osteoblast proliferation and mature osteoblast function. The net effect of exogenous PTH administration on bone turnover depends on the pattern of delivery. A continuous long-term infusion gives a net decrease in trabecular bone volume, whereas daily single injections result in a net increase. NPS Allelix Corp. is developing ALX1-11, recombinant human parathyroid hormone (1-84), for the treatment of osteoporosis. ALX1-11 is identical to the endogenous intact 84 amino acid human hormone and will be self-administered on a daily basis by subcutaneous (sc) injection. Currently, there is no approved therapy for osteoporosis capable of stimulating the formation of new bone of normal composition and structure. Most therapies in development are anti-catabolic and only prevent further bone loss (e.g., estrogen replacement, bisphosphonates, and calcitonins). ALX1-11 has the potential to stimulate new bone formation in osteoporotic patients, thereby increasing bone mass and preventing fractures. Patients with moderately or severely reduced bone density and a fracture would be expected to benefit from treatment, thereby improving functional status and alleviating symptoms.

Conditions

• Osteoporosis

Interventions

Type	Name	Description
DRUG	placebo	Daily subcutaneous injection with placebo
DRUG	ALX1-11	PTH (1-84) 100 mcg injected subcutaneously into the thigh or abdomen

Timeline

• Start date: 2000-04-27
• Primary completion: 2003-11-07
• Completion: 2003-11-07
• First posted: 2005-09-15
• Last updated: 2021-05-14

Locations

174 sites across 9 countries: United States, Argentina, Brazil, Bulgaria, Canada, Israel, Mexico, Romania, Russia