A First-in-human Study Evaluating AMG 785 in Healthy Men and Postmenopausal Women

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01059435
First received: January 28, 2010
Last updated: May 1, 2013
Last verified: May 2013
  Purpose

The primary objective of this study is to assess the safety and tolerability of AMG 785 following a single dose subcutaneous (SC) or intravenous (IV) administration in healthy men and postmenopausal women.


Condition Intervention Phase
Osteopenia
Drug: AMG 785
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Ascending Single-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 785 in Healthy Men and Postmenopausal Women

Further study details as provided by Amgen:

Primary Outcome Measures:
  • The number of subjects reporting treatment-emergent adverse events. [ Time Frame: Maximum of 85 days. ] [ Designated as safety issue: Yes ]
  • The number of subjects experiencing clinically significant changes in safety laboratory tests, physical examinations, vital signs, or electrocardiograms (ECGs). [ Time Frame: Maximum of 85 days. ] [ Designated as safety issue: Yes ]
  • The number of subjects who develop antibodies to AMG 785. [ Time Frame: Maximum of 85 days. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetic and pharmacodynamic parameters [serum procollagen type 1 N-terminal propeptide (P1NP), BSAP, osteocalcin, sCTX, intact parathyroid hormone (iPTH), serum and ionized calcium, and sclerostin levels]. [ Time Frame: Maximum of 85 days. ] [ Designated as safety issue: Yes ]

Enrollment: 74
Study Start Date: December 2006
Study Completion Date: August 2008
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: A
Two female subjects in each of cohorts 1, 2, 3a, 4, 5, and 6a will receive placebo; two male subjects in each of cohorts 3b and 6b; and 1 female subject in each of cohorts 3c and 6c.
Drug: AMG 785
Subjects will be randomized to receive 1 of 6 doses of AMG 785 or equivalent volume of placebo administered as a single dose. Postmenopausal women will receive AMG 785 or placebo as a weight-based dose of 0.1 mg/kg, 0.3, 1, 3, 5, or 10 mg/kg subcutaneously (SC, under the skin), or 1 mg/kg or 5 mg/kg intravenously (IV, in the vein), while men will receive doses of 1 mg/kg or 5 mg/kg SC or IV.
Active Comparator: B
Two female subjects in each of cohorts 1, 2, 3a, 4, 5, and 6a will receive AMG 785; two male subjects in each of cohorts 3b and 6b; and 1 female subject in each of cohorts 3c and 6c.
Drug: Placebo
Subjects will be randomized to receive 1 of 6 doses of AMG 785 or equivalent volume of placebo administered as a single dose. Postmenopausal women will receive AMG 785 or placebo as a weight-based dose of 0.1 mg/kg, 0.3, 1, 3, 5, or 10 mg/kg subcutaneously (SC, under the skin), or 1 mg/kg or 5 mg/kg intravenously (IV, in the vein), while men will receive doses of 1 mg/kg or 5 mg/kg SC or IV.

  Eligibility

Ages Eligible for Study:   45 Years to 59 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy males or female between 45 to 59 years of age, inclusive
  • Postmenopausal females defined as 12 continuous months of spontaneous amenorrhea confirmed by a serum follicle-stimulating hormone (FSH) result > 40mIU/mL, or 6 weeks postsurgical bilateral oophorectomy (with or without hysterectomy)
  • Males must agree to use a condom during sexual intercourse with female partners who are of reproductive potential and to have their female partners use an additional effective means of contraception or to abstain from sexual intercourse for the duration of the study
  • 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

Exclusion Criteria:

  • Diagnosed with any condition that will affect bone metabolism
  • 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
  • Routine alcohol intake of > 2 drinks per day, on average, within 6 months of study drug administration
  • Known sensitivity to mammalian-derived drug preparations
  • Known to be hepatitis B surface antigen, hepatitis C virus, or human immunodeficiency virus (HIV) positive, or a known diagnosis of acquired immunodeficiency syndrome (AIDS)
  • Any organic or psychiatric disorder which may pose a risk to subject safety and may prevent the subject from completing the study or interfere with the interpretation of the study results
  • 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 a history of drug or alcohol abuse with the last 12 months and/or a positive urine test result at screening or admission
  • Has any clinically significant abnormality during the screening physical examination, electrocardiogram (ECG), or laboratory evaluation
  • 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
  • Weight ≥ 98 kilograms (216 pounds) and/or height ≥ 78 inches
  • Has donated or lost 400 milliliters or more of blood or plasma within 8 weeks of study drug administration
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01059435

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Publications:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01059435     History of Changes
Other Study ID Numbers: 20060220
Study First Received: January 28, 2010
Last Updated: May 1, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Amgen:
Amgen
First in Human
Postmenopausal
Phase 1

Additional relevant MeSH terms:
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases

ClinicalTrials.gov processed this record on July 23, 2014