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

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

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.

Study Overview

• Status: Completed
• Conditions: Osteopenia
• Intervention / Treatment: Drug: AMG 167; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
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	168, 252, or 336 days following initial investigational product administration
Pharmacokinetics	168, 252, or 336 days following initial investigational product administration

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (ACTUAL): February 1, 2012
• Study Completion (ACTUAL): February 1, 2012

Study Registration Dates

• First Submitted: April 8, 2010
• First Submitted That Met QC Criteria: April 8, 2010
• First Posted (ESTIMATE): April 9, 2010

Study Record Updates

• Last Update Posted (ACTUAL): September 6, 2018
• Last Update Submitted That Met QC Criteria: September 4, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Phase 1b; Amgen; Postmenopausal; Bone Mineral Density
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic
• Other Study ID Numbers: 20080389