Safety and Efficacy of Abaloparatide-SC in Men With Osteoporosis (ATOM)

A Randomized, Double-blind, Placebo-controlled, Phase 3 Multicenter Study to Evaluate the Safety and Efficacy of Abaloparatide-SC for the Treatment of Men With Osteoporosis

A 12-month study to measure the efficacy and safety of abaloparatide in men with osteoporosis.

Study Overview

• Status: Completed
• Conditions: Osteoporosis; Age Related Osteoporosis; Osteoporosis, Age-Related; Osteoporosis Localized to Spine; Osteoporosis Senile; Osteoporosis of Vertebrae
• Intervention / Treatment: Drug: Abaloparatide; Drug: Placebo

Detailed Description

The primary objective of this prospective controlled study is to evaluate the efficacy and the safety of abaloparatide 80 micrograms (mcg) per day administered subcutaneously (SC) compared to placebo in men with osteoporosis. Efficacy was primarily assessed by the change in bone mineral density (BMD) over 12 months.

• Study Type: Interventional
• Enrollment (Actual): 228
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Verona, Italy, 37134
    • Azienda ospedaliera universitaria integrata di verona(AOUI)
  • Toscana
    • Siena, Toscana, Italy, 53100
      • Azienda Ospedaliera Universitaria Senese-Policlincio Santa Maria Alle Scotte
  • Tuscany
    • Florence, Tuscany, Italy, 50139
      • Azienda Ospedaliera Universitaria Careggi
• Poland
  • Białystok, Poland, 15-879
    • ClinicMed Daniluk, Nowak Sp.J.
  • Siedlce, Poland, 08-110
    • ETG Siedlce
  • Swidnik, Poland, 21-040
    • Lubelskie Centrum Diagnostyczne
  • Toruń, Poland, 87100
    • NZOZ Nasz Lekarz
  • Wrocław, Poland, 50-381
    • Synexus Polska Sp z o.o Oddzial we Wroclawiu
  • Łódź, Poland, 90-558
    • Centrum Leczenia Osteoporozy Klinika Zdrowej Kosci
  • Malopolskie
    • Kraków, Malopolskie, Poland, 31-501
      • Krakowskie Centrum Medyczne Sp. z o.o.
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 01-192
      • Synexus Polska Sp. z o.o. Oddzial w Warszawie
  • Podlaskie
    • Białystok, Podlaskie, Poland, 15-351
      • ZDROWIE OSTEO-MEDIC s.c. Lidia i Artur Racewicz, Agnieszka i Jerzy Supronik
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama At Birmingham
  • California
    • Greenbrae, California, United States, 94904
      • Marin Endocrine Care & Research, Inc.
    • Simi Valley, California, United States, 93065
      • Alta California Medical Group
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Colorado
    • Golden, Colorado, United States, 80401
      • Panorama Orthopedics & Spine Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown-MedStar Georgetown Transplant Institute University Hospital (MGUH)
  • Florida
    • Hialeah, Florida, United States, 33012
      • Indago Research & Health Center, Inc.
    • Miami, Florida, United States, 33156
      • Baptist Diabetes Associates, PA
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Center for Advanced Research & Education
    • Savannah, Georgia, United States, 31406
      • Meridian Clinical Research
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • The University Of Chicago
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • New Mexico Clinical Research & Osteoporosis Center, Inc.
  • New York
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • PMG Research of Cary, LLC
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington, LLC
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
  • Texas
    • Houston, Texas, United States, 77058
      • Centex Studies, Inc.
    • McAllen, Texas, United States, 78504
      • Centex Studies, Inc
  • Virginia
    • Richmond, Virginia, United States, 23249
      • Hunter Holmes McGuire VA Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin Osteoporosis Clinical Research Program

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Key Inclusion Criteria

• Healthy ambulatory male from 40 to 85 years of age (inclusive) with primary osteoporosis or osteoporosis associated with hypogonadism.
• The participant has a BMD T-score based on female or male reference range (depending on date of enrollment) as assessed by the central imaging vendor of ≤ -2.5 at the lumbar spine (L1-L4) or hip (femoral neck or total hip) by dual energy X-ray absorptiometry (DXA) or ≤ -1.5 and with radiologic evidence of vertebral fracture or a documented history of low-trauma nonvertebral fracture sustained in the past 5 years. Men older than 65 years may be enrolled if they have a BMD T-score ≤ -2.0 even if they do not meet the fracture criteria.
• Normal medical history, physical examination, including vital signs, and body mass index.
• Hypogonadal participants whose doses of androgens have been stable for at least twelve months before randomization are eligible and may continue therapy during the study.
• Laboratory tests within the normal range including serum calcium (albumin-corrected), parathyroid hormone, serum phosphorus and alkaline phosphatase, and thyroid stimulating hormone values.

Key Exclusion Criteria

• Presence of abnormalities of the lumbar spine that would prohibit assessment of spinal BMD, defined as having at least 2 radiologically evaluable vertebrae within L1-L4.
• A BMD T-score of ≤-3.5 at the total hip, femoral neck, or lumbar spine based on female or male reference range (depending on date of enrollment).
• Unevaluable hip BMD or participants who have undergone bilateral hip replacement.
• Fragility fracture within the prior twelve months.
• History of severe vertebral fracture or >2 moderate vertebral fractures.
• History of bone disorders (for example, Paget's disease) other than osteoporosis.
• participant with clinical signs of hypogonadism present at screening who plan to initiate testosterone replacement.
• History of prior external beam or implant radiation therapy involving the skeleton other than radioiodine.
• History of chronic or recurrent renal, hepatic, pulmonary, allergic, cardiovascular, gastrointestinal, endocrine, central nervous system, hematologic or metabolic diseases, or immunologic, emotional and/or psychiatric disturbances to a degree that would interfere with the interpretation of study data or compromise the safety of the participant.
• History of Cushing's disease, growth hormone deficiency or excess, hyperthyroidism, hypo- or hyperparathyroidism or malabsorptive syndromes within the past year.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abaloparatide; Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen that delivers 30 doses. Participants received a new injection pen every 30 days.	Drug: Abaloparatide; Abaloparatide is a synthetic peptide that is a potent and selective activator of the parathyroid hormone 1 receptor signaling pathway.; Other Names: TYMLOS®; BA058; abaloparatide-SC
Placebo Comparator: Placebo; Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen that delivers 30 doses. Participants received a new injection pen every 30 days.	Drug: Placebo; Abaloparatide-matched placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Lumbar Spine BMD at Month 12	Lumbar Spine BMD was assessed by DXA scans evaluated by a central imaging laboratory. Lumbar spine scans included L1 through L4. Positive changes from baseline indicate improvement in bone health.	Baseline, Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Total Hip BMD at Month 12	Total hip BMD was assessed by DXA scans evaluated by a central imaging laboratory. Positive changes from baseline indicate improvement in bone health.	Baseline, Month 12
Percent Change From Baseline in Femoral Neck BMD at Month 12	Femoral neck BMD was assessed by DXA scans evaluated by a central imaging laboratory. Positive changes from baseline indicate improvement in bone health.	Baseline, Month 12
Percent Change From Baseline in Lumbar Spine BMD at Month 6	Lumbar Spine BMD was assessed by DXA scans evaluated by a central imaging laboratory. Lumbar spine scans included L1 through L4. Positive changes from baseline indicate improvement in bone health.	Baseline, Month 6
Percent Change in Total Hip BMD From Baseline at Month 6	Total hip BMD was assessed by DXA scans evaluated by a central imaging laboratory. Positive changes from baseline indicate improvement in bone health.	Baseline, Month 6
Percent Change From Baseline in Femoral Neck BMD at Month 6	Femoral neck BMD was assessed by DXA scans evaluated by a central imaging laboratory. Positive changes from baseline indicate improvement in bone health.	Baseline, Month 6
Percent Change From Baseline in Ultra-Distal Radius BMD at Month 12	Ultra-distal radius BMD was assessed by DXA scans. Positive changes from baseline indicate improvement in bone health.	Baseline, Month 12
Percent Change From Baseline in Distal One-third Radius BMD at Month 12	Distal one-third radius BMD was assessed by DXA scans. Positive changes from baseline indicate improvement in bone health.	Baseline, Month 12
Percent Change From Baseline in Serum Procollagen Type I N-terminal Propeptide (s-PINP) at Month 12	Blood samples were taken to measure s-PINP, a bone formation marker. s-PINP concentrations reflect the rate of skeletal new bone formation. Increases in s-PINP indicate anabolic biologic response in the bone.	Baseline, Month 12
Percent Change From Baseline in Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) at Month 12	Blood samples were taken to measure s-CTX. Elevated levels of s-CTX indicate increased bone resorption (bone loss).	Baseline, Month 12
Number of Participants With New Clinical Fractures	Radiological evaluations were performed to identify any new clinical fractures (occurring after the screening visit).	Baseline through Month 12
Percent of Participants With Change in Disease Status	The percentage of participants converting from the categories of osteoporosis to osteopenia or from osteopenia to normal at End of Treatment (Month 12) was assessed. Osteoporosis was defined as lumbar spine or total hip BMD T-score ≤ -2.5. Osteopenia was defined as one of the following: Lumbar spine > -2.5 and total hip BMD T-score > -2.5 and < -1.0; Lumbar spine > -2.5 and < -1.0 and total hip BMD T-score > -2.5; Normal was defined as lumbar spine and total hip BMD T-score ≥ -1.0.	Baseline through Month 12
Percent of Participants Experiencing BMD Gains From Baseline of > 0%, > 3%, and > 6% at the Lumbar Spine, Femoral Neck, and Total Hip	Lumbar spine, femoral neck, and total hip BMD were assessed by DXA scans evaluated by a central imaging laboratory.	Month 12
Percent Change From Baseline in Total Hip Volumetric BMD as Measured by Quantitative Computed Tomography (QCT) at Month 12	QCT scans were evaluated by a central imaging laboratory.	Baseline, Month 12
Percent Change From Baseline in Femoral Neck Volumetric BMD as Measured by QCT at Month 12	QCT scans were evaluated by a central imaging laboratory.	Baseline, Month 12

Collaborators and Investigators

• Sponsor: Radius Health, Inc.
• Investigators: Study Director: Sr. Director, Clinical Operations, Radius Health, Inc.

Publications and helpful links

General Publications

• Rizzoli R, Bonjour JP, Ferrari SL. Osteoporosis, genetics and hormones. J Mol Endocrinol. 2001 Apr;26(2):79-94. doi: 10.1677/jme.0.0260079.
• Mannstadt M, Juppner H, Gardella TJ. Receptors for PTH and PTHrP: their biological importance and functional properties. Am J Physiol. 1999 Nov;277(5):F665-75. doi: 10.1152/ajprenal.1999.277.5.F665.
• Dempster DW, Cosman F, Parisien M, Shen V, Lindsay R. Anabolic actions of parathyroid hormone on bone. Endocr Rev. 1993 Dec;14(6):690-709. doi: 10.1210/edrv-14-6-690. No abstract available. Erratum In: Endocr Rev 1994 Apr;15(2):261.

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2018
• Primary Completion (Actual): August 17, 2021
• Study Completion (Actual): September 8, 2021

Study Registration Dates

• First Submitted: April 17, 2018
• First Submitted That Met QC Criteria: April 26, 2018
• First Posted (Actual): April 30, 2018

Study Record Updates

• Last Update Posted (Actual): April 7, 2023
• Last Update Submitted That Met QC Criteria: April 6, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: osteoporosis; fracture; male osteoporosis; bone loss; BA058; abaloparatide; abaloparatide-SC; TYMLOS®
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Parathyroid Hormone-Related Protein; Abaloparatide
• Other Study ID Numbers: BA058-05-019; ATOM (Other Identifier: Radius Health, Inc.)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No