An Ascending Multiple Dose Study Evaluating AMG 167 in Healthy Men and Postmenopausal Women With Low Bone Mineral Density

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01101048
First received: April 8, 2010
Last updated: October 15, 2012
Last verified: October 2012
  Purpose

The purpose of this study is to assess the safety, tolerability, and potential immune response of AMG 167 following multiple subcutaneous (SC, injection under the skin) dose administrations in healthy men and postmenopausal women with low bone mineral density.


Condition Intervention Phase
Osteopenia
Drug: Placebo
Drug: AMG 167
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Ascending Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 167 in Healthy Men and Postmenopausal Women With Low Bone Mineral Density

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • The number (percent) of subjects experiencing clinically significant changes in safety laboratory tests, physical examinations, vital signs, or electrocardiograms (ECGs) [ Time Frame: 168, 252, or 336 days following initial investigational product administration ] [ Designated as safety issue: Yes ]
  • The number (percent) of subjects reporting treatment-emergent adverse events [ Time Frame: 168, 252, or 336 days following initial investigational product administration ] [ Designated as safety issue: Yes ]
  • The number (percent) of subjects who develop anti-AMG 167 antibodies [ Time Frame: 168, 252, or 336 days following initial investigational product administration ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacodynamic parameters [bone mineral density as assessed by dual energy X-ray absorptiometry (DXA), serum procollagen type 1 N-terminal propeptide (P1NP), osteocalcin, bone-specific alkaline phosphatase (BSAP), and serum CTX levels] and sclerostin [ Time Frame: 168, 252, or 336 days following initial investigational product administration ] [ Designated as safety issue: No ]
  • Pharmacokinetics [ Time Frame: 168, 252, or 336 days following initial investigational product administration ] [ Designated as safety issue: No ]

Enrollment: 74
Study Start Date: June 2010
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: A
Two (2) women in each of cohorts 1 and 4, and two (2) men in cohort 2 will receive placebo every 2 weeks for a total of 6 doses. Two (2) women in each of cohorts 3 and 5, and two (2) men in cohort 6 will receive placebo every 4 weeks for a total of 3 doses. Six (6) women in cohort 7 will receive placebo every 2 weeks for a total of 12 doses. In addition, subjects in cohorts 4 have the option to receive an additional 6 doses of placebo; subjects in cohorts 5 and 6 have the option to receive an additional 3 doses. Subjects in cohort 7 have the option to transition to 6 months of alendronate treatment.
Drug: AMG 167
Subjects will be randomized to receive one of 3 doses of AMG 167 or equivalent volume of placebo administered at once every two-week or once every four-week dosing intervals. Postmenopausal women will receive AMG 167 in one of 3 fixed doses, while men will receive AMG 167 in one of 2 fixed doses by injection under the skin.
Active Comparator: B
Six (6) women in each of cohorts 1 and 4, and six (6) men in cohort 2 will receive AMG 167 every 2 weeks for a total of 6 doses. Six (6) women in each of cohorts 3 and 5, and six (6) men in cohort 6 will receive AMG 167 every 4 weeks for a total of 3 doses. Eighteen (18) women in cohort 7 will receive AMG 167 every 2 weeks for a total of 12 doses. In addition, subjects in cohorts 4 have the option to receive an additional 6 doses of AMG 167; subjects in cohorts 5 and 6 have the option to receive an additional 3 doses. Subjects in cohort 7 have the option to transition to 6 months of alendronate treatment.
Drug: Placebo
Subjects will be randomized to receive one of 3 doses of AMG 167 or equivalent volume of placebo administered at once every two-week or once every four-week dosing intervals. Postmenopausal women will receive AMG 167 in one of 3 fixed doses, while men will receive AMG 167 in one of 2 fixed doses by injection under the skin.

  Eligibility

Ages Eligible for Study:   45 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Low bone mineral density as determined at the time of screening [as defined by bone mineral density (BMD) T-scores of the lumbar spine (L1-L4), or total evaluable vertebrae (if fewer than L1-L4); or femoral neck between -1.0 and -2.5, exclusive]
  • 25-hydroxyvitamin D ≥ 20 ng/mL
  • Willing and able to take ≥ 1,000 mg elemental calcium and ≥ 800 IU (but ≤ 1,000 IU) vitamin D daily upon enrollment

Exclusion Criteria:

  • Osteoporosis, as defined by BMD T-scores of the lumbar spine (L1-L4) or total evaluable vertebrae (if fewer than L1-L4); or femoral neck ≤ 2.5
  • History of vertebral fracture, or fragility fracture (a fracture resulting from no or minor trauma; ie, fall from standing height or less) of the wrist, humerus, hip, or pelvis after age 50
  • Diagnosed with any condition that will affect bone metabolism
  • Diagnosis of clotting factor deficiency or history of bleeding or coagulation disorder
  • History of spinal stenosis
  • History of facial nerve paralysis

Exclusion Criteria for Cohort 7 Sub-study (Transition to Alendronate):

  • Contraindicated or intolerant of alendronate therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01101048

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01101048     History of Changes
Other Study ID Numbers: 20080389
Study First Received: April 8, 2010
Last Updated: October 15, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Amgen:
Amgen
Phase 1b
Postmenopausal
Bone Mineral Density

ClinicalTrials.gov processed this record on September 18, 2014