Clinical trial NCT00902356: A First-in-human Study Evaluating AMG 167 in Healthy Men and Postmenopausal Women
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Osteopenia
Keywords: Amgen
Phase 1
First in Human
Postmenopausal
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2009-05-15
Enrollment: 69
Sex: ALL
Minimum age (years): 45
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)
* 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

Primary outcomes:
measure: The number (percent) of subjects reporting treatment-emergent adverse events.
timeFrame: Cohort 1 - 29 days; cohorts 2, 3, 6, and 7 - 57 days; cohorts 4, 5, 8, and 9 - 85 days
measure: The number of subjects experiencing clinically significant changes in safety laboratory tests, physical examinations, vital signs, or electrocardiograms (ECGs).
timeFrame: Cohort 1 - 29 days; cohorts 2, 3, 6, and 7 - 57 days; cohorts 4, 5, 8, and 9 - 85 days
measure: The number of subjects who develop anti-AMG 167 antibodies.
timeFrame: Cohort 1 - 29 days; cohorts 2, 3, 6, and 7 - 57 days; cohorts 4, 5, 8, and 9 - 85 days
Secondary outcomes:
measure: 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.
timeFrame: Cohort 1 - 29 days; cohorts 2, 3, 6, and 7 - 57 days; cohorts 4, 5, 8, and 9 - 85 days
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: