A Randomized, Double-blind, Placebo-controlled, Ascending Single-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 167 in Healthy Men and Postmenopausal Women
Overview
- Phase
- Phase 1
- Intervention
- Placebo
- Conditions
- Osteopenia
- Sponsor
- Amgen
- Enrollment
- 69
- Primary Endpoint
- The number (percent) of subjects reporting treatment-emergent adverse events.
- Status
- Completed
- Last Updated
- 16 years ago
Overview
Brief Summary
The primary objective of this study is to determine the safety and tolerability of AMG 167 following a single dose subcutaneous (SC) or intravenous (IV) administration in healthy men and postmenopausal women.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy males and females between 45 to 65 years of age
- •Postmenopausal females defined as 12 continuous months of spontaneous amenorrhea confirmed by a serum follicle-stimulating hormone (FSH) result \> 40mIU/mL, or at least 6 weeks postsurgical bilateral oophorectomy (with or without hysterectomy)
- •Men must agree to use highly effective methods of contraception; males must agree to not donate sperm for the entire study and 7 months after the end of treatment
- •Weight ≤ 98 kg (216 lb) and/or height ≤ 196 cm (77 in)
- •Has no history or evidence of a clinically significant disorder, condition or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
- •Negative urine screen for potential drugs of abuse at screening and admission, unless medication is prescribed by a physician
Exclusion Criteria
- •Healthy males with partners who are pregnant at the time of screening; or healthy males with partners who plan to become pregnant during the study
- •Osteoporosis, as defined by BMD t-scores of the lumbar spine (L1-L4) or total evaluable vertebrae; or femoral neck ≤ 2.5
- •Diagnosed with any condition that will affect bone metabolism
- •Diagnosis of clotting factor deficiency or history of bleeding or coagulation disorder (including history of heparin or warfarin administration)
- •Subjects with fewer than 2 evaluable vertebrae; metal in hips bilaterally that would not allow for at least one evaluable hip; metal in forearms bilaterally that would not allow for at least one evaluable forearm
- •Abnormal international normalized ratio or partial thromboplastin time
- •Administration of the following medications within 6 months before study drug administration:
- •Hormone replacement therapy \[Infrequent use of estrogen vaginal creams (\< 3 times per week) is allowed.\]
- •Calcitonin
- •Parathyroid hormone (or any derivative)
Arms & Interventions
B
Six female subjects in each of cohorts 1 to 5 will receive AMG 167; six male subjects in each of cohorts 6 and 8; three female subjects in each of cohorts 7 and 9.
Intervention: Placebo
A
Two female subjects in each of cohorts 1 to 5 will receive placebo; two male subjects in each of cohorts 6 and 8; and 1 female subject in each of cohorts 7 and 9.
Intervention: AMG 167
Outcomes
Primary Outcomes
The number (percent) of subjects reporting treatment-emergent adverse events.
Time Frame: Cohort 1 - 29 days; cohorts 2, 3, 6, and 7 - 57 days; cohorts 4, 5, 8, and 9 - 85 days
The number of subjects experiencing clinically significant changes in safety laboratory tests, physical examinations, vital signs, or electrocardiograms (ECGs).
Time Frame: Cohort 1 - 29 days; cohorts 2, 3, 6, and 7 - 57 days; cohorts 4, 5, 8, and 9 - 85 days
The number of subjects who develop anti-AMG 167 antibodies.
Time Frame: Cohort 1 - 29 days; cohorts 2, 3, 6, and 7 - 57 days; cohorts 4, 5, 8, and 9 - 85 days
Secondary Outcomes
- Pharmacokinetic and phamacodynamic parameters [serum procollagen type 1 N-terminal propeptide (P1NP), BSAP, osteocalcin, sCTX, sclerostin levels, and bone mineral density (BMD) for higher dose levels] after single dose SC or IV administration of AMG 167.(Cohort 1 - 29 days; cohorts 2, 3, 6, and 7 - 57 days; cohorts 4, 5, 8, and 9 - 85 days)