Clinical trial NCT00950950: A Study to Evaluate the Effect of Romosozumab (AMG 785) on Bone Quality of the Forearm in Postmenopausal Women With Low Bone Mass
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Osteopenia
Keywords: Amgen
Postmenopausal
Bone Density
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2009-08-03
Enrollment: 24
Sex: FEMALE
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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
  * Calcitriol, and available analogues
* Administration of daily, weekly, or monthly bisphosphonates (BP) unless meeting the following criteria:

  * \< 2 weeks of BP use requires a 2-month washout period
  * 2 weeks to 3 months of BP use requires a 9-month washout period
  * 3 to 6 months of BP use requires a 1-year washout period
  * \> 6 months of BP use requires a 3-year washout period;
* Greatly differing levels of physical activity or constant levels of intense physical exercise during the 6 months before study drug administration
* Known sensitivity to mammalian-derived drug preparations
* Known to be hepatitis B surface antigen, hepatitis C virus or human Immunodeficiency virus (HIV) positive or a known diagnosis of acquired immunodeficiency syndrome (AIDS)
* Any organic or psychiatric disorder, which, in the opinion of the investigator, poses a risk to subject safety and may prevent the subject from completing the study or interfere with the interpretation of the study results
* Unavailable for follow-up assessment or any concerns for subject's compliance with the protocol procedures
* Any other condition that might reduce the chance of obtaining data required by the protocol or that might compromise the ability to give truly informed consent
* History or evidence of a clinically significant disorder, condition or disease that, in the opinion of the Investigator or Amgen physician would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
* Clinically significant abnormality during the screening physical examination, electrocardiogram (ECG) or laboratory evaluation
* Participation in another clinical study within 4 weeks of screening or within 5 times the half-life of the investigational agent in the other clinical study, if known
* Has donated or lost 400 mL or more of blood or plasma within 8 weeks of study drug administration
* Previous AMG 785 exposure

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