A First-in-human Study Evaluating AMG 167 in Healthy Men and Postmenopausal Women
- Registration Number
- NCT00902356
- Lead Sponsor
- Amgen
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 69
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)
- Supplemental Vitamin D > 1,000 IU/day
- Glucocorticosteroids (inhaled or topical corticosteroids administered more than 2 weeks before the enrollment date are allowed)
- Anabolic steroids
- Calcitriol, and available analogues
- Administration of the following medications within 12 months before study drug administration:
- Bisphosphonates
- Fluoride for osteoporosis
- Administration of herbal medications within 2 weeks or 5 half-lives (whichever is longer) before study drug administration
- Greatly differing levels of physical activity or constant levels of intense physical exercise during the 6 months before study drug administration
- Known alcohol abuse or use of illicit drugs within 12 months of admission
- Unwilling or unable to limit alcohol consumption throughout the course of the study
- Known sensitivity to mammalian-derived drug preparations
- Known to be hepatitis B surface antigen, hepatitis C virus, or human immunodeficiency virus positive, or a known diagnosis of acquired immunodeficiency syndrome
- An unstable medical condition, defined as having been hospitalized within 28 days before day -1, major surgery within 6 months before day -1, or otherwise unstable in the judgment of the investigator
- Has any clinically significant abnormality during the screening physical examination, ECG, or laboratory evaluation
- 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
- Has participated 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 exposure to AMG 785
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description B Placebo 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. A AMG 167 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.
- Primary Outcome Measures
Name Time Method The number (percent) of subjects reporting treatment-emergent adverse events. 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). 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. Cohort 1 - 29 days; cohorts 2, 3, 6, and 7 - 57 days; cohorts 4, 5, 8, and 9 - 85 days
- Secondary Outcome Measures
Name Time Method 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