A Randomized, Double-blind, Placebo-controlled, Multiple Dose Study to Evaluate the Effect of AMG 785 on Parameters of Bone Quality of the Forearm Using pQCT in Postmenopausal Women With Low Bone Mineral Density

Amgen0 sites24 target enrollmentAugust 18, 2009

ConditionsOsteopenia

InterventionsPlacebo Romosozumab

DrugsRomosozumab Placebo

Overview

Phase: Phase 1
Intervention: Placebo
Conditions: Osteopenia
Sponsor: Amgen
Enrollment: 24
Primary Endpoint: Percent Change From Baseline in Polar Cross-sectional Moment of Inertia at the Distal Radius
Status: Completed
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

The purpose of this study is to evaluate the effect of romosozumab on parameters of bone quality of the forearm using peripheral quantitative computed tomography (pQCT) following multiple subcutaneous dose administrations of romosozumab in postmenopausal women with low bone mass.

Registry

clinicaltrials.gov

Start Date

August 18, 2009

End Date

August 19, 2010

Last Updated

6 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Female

Investigators

Sponsor

Amgen

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Healthy females between 55 to 80 years of age
•Postmenopausal females (based on medical history) defined as 12 continuous months of spontaneous amenorrhea
•Women 60 years of age and older will be considered postmenopausal
•Women 55-59 must have a serum follicle-stimulating hormone result \> 40 mIU/mL and serum estradiol ≤ 20 pg/mL
•Low bone mineral density (BMD), defined as a BMD T-score between -1.0 and -2.5 at the lumbar spine (L1-L4) and/or femoral neck
•Weight ≤ 98 kg (216 lb) and/or height ≤ 196 cm (77 in)
•25-hydroxyvitamin D ≥ 20 ng/mL at screening
•Willing and able to take ≥ 500 mg calcium and ≥ 400 IU (but ≤ 1,000 IU) vitamin D daily

Exclusion Criteria

•Osteoporosis, defined as a BMD T-score ≤ -2.5 at the lumbar spine or femoral neck
•History of vertebral fracture, or fragility fracture of the wrist, humerus, hip or pelvis
•Diagnosed with any condition that will affect bone metabolism
•Subjects with fewer than 2 evaluable vertebrae; metal in forearms bilaterally that would not allow for at least one evaluable forearm
•Administration of the following medications within 6 months before study drug administration. This includes all routes of administration, for example intranasal and topical skin patches, unless otherwise noted:
•Hormone replacement therapy \[(eg, estrogen, estrogen-like compounds such as raloxifene). Infrequent use of estrogen vaginal creams (\< 3 times per week) is allowed.\]
•Calcitonin
•Parathyroid hormone (or any derivative)
•Glucocorticosteroids (inhaled or topical corticosteroids administered more than 2 weeks before the enrollment date are allowed)
•Anabolic steroids

Arms & Interventions

Placebo

Participants were randomized to receive matching placebo administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.

Intervention: Placebo

Romosozumab

Participants were randomized to receive 3 mg/kg romosozumab administered by subcutaneous injection once every 4 weeks (Q4W) for 3 months.

Intervention: Romosozumab

Outcomes

Primary Outcomes

Percent Change From Baseline in Polar Cross-sectional Moment of Inertia at the Distal Radius

Time Frame: Baseline and days 29, 57, 85, 127, and 169

The polar moment of inertia is a geometric measurement used to predict bone quality, specifically the ability to resist torsion (twisting), and is highly correlated with fracture load at the distal radius. The polar cross-sectional moment of inertia was assessed using peripheral quantitative computed tomography (pQCT), a 3-dimensional imaging technology which can be used for volumetric analysis of appendicular skeletal sites such as the arms and the legs. The distal slice was acquired at 20% of the length of the ulna proximal to the radial endplate. Scans were analyzed by a central reader.

Secondary Outcomes

Percent Change From Baseline in Cortical Bone Area at the Distal Radius(Baseline and days 29, 57, 85, 127, and 169)
Percent Change From Baseline in Total Bone Area at the Distal Radius(Baseline and days 29, 57, 85, 127, and 169)
Percent Change From Baseline in Total Bone Mineral Content at the Distal Radius(Baseline and days 29, 57, 85, 127, and 169)
Percent Change From Baseline in Periosteal Circumference at the Distal Radius(Baseline and days 29, 57, 85, 127, and 169)
Percent Change From Baseline in Cortical Thickness at the Distal Radius(Baseline and days 29, 57, 85, 127, and 169)
Percent Change From Baseline in Polar Section Modulus at the Distal Radius(Baseline and days 29, 57, 85, 127, and 169)
Percent Change From Baseline in Polar Strength Strain Index at the Distal Radius(Baseline and days 29, 57, 85, 127, and 169)
Percent Change From Baseline in Axial Moment of Inertia at the Distal Radius(Baseline and days 29, 57, 85, 127, and 169)
Percent Change From Baseline in Total Bone Mineral Density at the Distal Radius(Baseline and days 29, 57, 85, 127, and 169)
Percent Change From Baseline in Cortical Bone Mineral Content at the Distal Radius(Baseline and days 29, 57, 85, 127, and 169)
Percent Change From Baseline in Cortical Bone Mineral Density at the Distal Radius(Baseline and days 29, 57, 85, 127, and 169)
Percent Change From Baseline in Endocortical Circumference at the Distal Radius(Baseline and days 29, 57, 85, 127, and 169)
Percent Change From Baseline in Trabecular Bone Mineral Content at the Ultradistal Radius(Baseline and days 29, 57, 85, 127, and 169)
Percent Change From Baseline in Trabecular Bone Mineral Density at the Ultradistal Radius(Baseline and days 29, 57, 85, 127, and 169)
Percent Change From Baseline in Polar Strength Strain Index at the Ultradistal Radius(Baseline and days 29, 57, 85, 127, and 169)
Percent Change From Baseline in Bone Mineral Density at the One-third Radius(Baseline and days 29, 57, 85, 127, and 169)
Percent Change From Baseline in Bone Mineral Density at the Total Wrist(Baseline and days 29, 57, 85, 127, and 169)
Percent Change From Baseline in Bone Mineral Density at the Total Lumbar Spine(Baseline and days 85 and 169)
Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)(Baseline and days 4, 15, 29, 57, 62, 71, 85, 99, 127, and 169)
Percent Change From Baseline in Serum C-Telopeptide (sCTX)(Baseline and days 4, 15, 29, 57, 62, 71, 85, 99, 127, and 169)
Time to Maximum Serum Concentration (Tmax) of Romosozumab(First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169)
Percent Change From Baseline in Total Bone Area at the Ultradistal Radius(Baseline and days 29, 57, 85, 127, and 169)
Percent Change From Baseline in Total Bone Mineral Content at the Ultradistal Radius(Baseline and days 29, 57, 85, 127, and 169)
Percent Change From Baseline in Total Bone Mineral Density at the Ultradistal Radius(Baseline and days 29, 57, 85, 127, and 169)
Percent Change From Baseline in Trabecular Bone Area at the Ultradistal Radius(Baseline and days 29, 57, 85, 127, and 169)
Maximum Serum Concentration (Cmax) of Romosozumab(First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169)
Area Under the Serum Concentration-time Curve From Time 0 to Tau (AUC0-28)(First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169)
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf)(Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169)
Apparent Clearance (CL/F) of Romosozumab(Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169)
Terminal Half-life (t1/2,z) of Romosozumab(Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169)
Accumulation Ratio(First Dose: Day 1 (predose) and on days 4, 15, and 29 (predose). Last Dose: Days 57 (predose), 62, 71, 85, 99, 127, and 169)