Study to Compare the Efficacy and Safety of DenosumAb Versus Placebo in Males With Osteoporosis

NCT00980174 | Completed Phase 3 Results

• 1 other identifier: 20080098
• Study Type: interventional
• Target: 242
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to assess how effective and safe denosumab is in a population of males with low bone mass at risk of fracture. The primary clinical hypothesis is that in men with low bone mineral density, the mean percent change in lumbar spine bone mineral density at 12 months in subjects receiving denosumab will be greater than in subjects receiving placebo. Denosumab is a fully human monoclonal antibody with a high affinity for Receptor Activator of Nuclear Factor (RANK) Ligand that can bind and neutralize the activity of human RANK Ligand similar to the action of endogenous osteoprotegerin.

Conditions

Low Bone Mass; Low Bone Mineral Density; Males With Osteoporosis; Osteopenia; Osteoporosis

Keywords

men; male; denosumab; BMD; lumbar spine; ADAMO; The ADAMO Trial; male osteoporosis; osteoporosis in men; males with low bone mineral density

Outcome Measures

Primary Outcomes (1)

• Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12

  From Baseline to 12 Months

Secondary Outcomes (5)

• Total Hip Bone Mineral Density Percent Change From Baseline at Month 12

  From Baseline to 12 Months

• Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 12

  From Baseline to 12 Months

• Trochanter Bone Mineral Density Percent Change From Baseline at Month 12

  From Baseline to 12 Months

• Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12

  From Baseline to 12 Months

• Serum Type 1 Collagen C-telopeptide (CTX) Percent Change From Baseline at Day 15

  From Baseline to Day 15

Study Arms (2)

2

PLACEBO COMPARATOR

Subjects will receive placebo for denosumab (SC injection every 6 months) for 1 year (double-blind phase) followed by 60 mg denosumab (SC injection every 6 months) for 1 year (open-label phase)

Drug: 60 mg denosumab; Other: Placebo

1

EXPERIMENTAL

60 mg denosumab (SC injection every 6 months) for 1 year (double-blind phase) followed by 60 mg denosumab(SC injection every 6 months) for 1 year (open-label phase). These subjects will be on denosumab for a total of 2 years.

Drug: 60 mg denosumab

Interventions

60 mg denosumab DRUG

60 mg denosumab (SC injection every 6 months)

Also known as: denosumab

1; 2

Placebo OTHER

Placebo for denosumab (SC injection every 6 months)

2

Eligibility Criteria

• Age: 30 Years - 85 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Bone Mineral Density (BMD) values (g/cm2) assessed by the local site at either the lumbar spine OR femoral neck that occur within the ranges specified in the protocol OR For subjects with a history of a major osteoporotic fracture (clinical vertebral, hip, humerus and distal radius fractures) occurring more than 6 months prior to screening, BMD values (g/cm2) assessed by the local site, at either the lumbar spine OR femoral neck that occur within the ranges specified in the protocol.
• At least 2 lumbar vertebrae, at least 1 hip and at least one forearm must be evaluable by Dual X ray Absorptiometry (DXA).
• Ambulatory males 30 to 85 years of age inclusive at the start of screening.
• Provide the appropriate written informed consent before any study specific procedure.

You may not qualify if:

• BMD values (g/cm2) as specified in the protocol in subjects with or without a history of major osteoporotic fractures, based on the particular scanner that is used.
• Any disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.
• Any severe or more than 1 moderate vertebral fractures on screening spinal x ray
• Any vertebral fracture diagnosed within the 6 months prior to screening
• Any clinical fracture within the last 6 months prior to screening
• For males with a partner of childbearing potential: Subject refuses to use 2 highly effective methods of contraception for the duration of the study and for 10 months after the last dose of study medication.
• For males with a partner who is pregnant: Subject refuses to use a condom for the duration of the study and for 10 months after the last dose of study medication.
• Previous participation in clinical trials with denosumab or administration of commercial denosumab.
• Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s).
• Vitamin D deficiency \[25(OH) vitamin D level \< 20 ng/mL (\< 49.9 nmol/L)\]. Vitamin D replenishment will be permitted and subjects may be re-screened; see Section 7.
• Hyper- or hypothyroidism; however, stable subjects, in the investigator's opinion, on thyroid hormone replacement therapy are allowed.
• Hyper- or hypoparathyroidism. Intact parathyroid hormone (iPTH) values outside of the reference range as determined by the central laboratory
• Elevated transaminases. Serum aspartate aminotransferase; serum glutamate-oxaloacetic transaminase \> 2.5 x upper limit of normal. Serum alanine aminotransferase; serum glutamate pyruvate transaminase \> 2.5 x upper limit of normal (both as determined by the central laboratory).
• Significantly impaired renal function as determined by a derived glomerular filtration rate (using the Modification of Diet in Renal Disease formula) of less than or equal to 30 mL/min/1.73 m2 calculated by the central laboratory.
• Hypo- or hypercalcemia based on the central laboratory reference ranges for albumin-adjusted serum calcium.

Sponsors & Collaborators

• Amgen: lead

Related Publications (2)

• Langdahl BL, Teglbjaerg CS, Ho PR, Chapurlat R, Czerwinski E, Kendler DL, Reginster JY, Kivitz A, Lewiecki EM, Miller PD, Bolognese MA, McClung MR, Bone HG, Ljunggren O, Abrahamsen B, Gruntmanis U, Yang YC, Wagman RB, Mirza F, Siddhanti S, Orwoll E. A 24-month study evaluating the efficacy and safety of denosumab for the treatment of men with low bone mineral density: results from the ADAMO trial. J Clin Endocrinol Metab. 2015 Apr;100(4):1335-42. doi: 10.1210/jc.2014-4079. Epub 2015 Jan 21.

  PMID: 25607608 BACKGROUND

• Orwoll E, Teglbjaerg CS, Langdahl BL, Chapurlat R, Czerwinski E, Kendler DL, Reginster JY, Kivitz A, Lewiecki EM, Miller PD, Bolognese MA, McClung MR, Bone HG, Ljunggren O, Abrahamsen B, Gruntmanis U, Yang YC, Wagman RB, Siddhanti S, Grauer A, Hall JW, Boonen S. A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density. J Clin Endocrinol Metab. 2012 Sep;97(9):3161-9. doi: 10.1210/jc.2012-1569. Epub 2012 Jun 21.

  PMID: 22723310 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Bone Diseases, Metabolic; Osteoporosis; Multiple Endocrine Neoplasia Type 1

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Multiple Endocrine Neoplasia; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2009
• First Posted: September 18, 2009
• Study Start: October 1, 2009
• Primary Completion: June 21, 2011
• Study Completion: May 23, 2012
• Last Updated: October 17, 2018
• Results First Posted: November 29, 2012

Record last verified: 2018-09