A First-in-human Study Evaluating AMG 167 in Healthy Men and Postmenopausal Women

Phase 1

Completed

• Conditions: Osteopenia
• Interventions: Drug: Placebo; Drug: AMG 167

• 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

Study Timeline

• Study Start: 2009-05
• Study First Submitted: 2009-05-14
• Study First Submitted QC: 2009-05-14
• Study First Posted: 2009-05-15
• Primary Completion: 2009-11
• Study Completion: 2009-11
• Status Verified: 2010-04
• Last Update Submitted: 2010-04-01
• Last Update Posted: 2010-04-02

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