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Trial record 74 of 108 for:    CALCIUM CATION

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

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ClinicalTrials.gov Identifier: NCT01059435
Recruitment Status : Completed
First Posted : February 1, 2010
Results First Posted : July 4, 2019
Last Update Posted : July 4, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

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

Condition or disease Intervention/treatment Phase
Osteopenia Drug: Romosozumab Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 74 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, 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
Actual Study Start Date : December 13, 2006
Actual Primary Completion Date : July 6, 2007
Actual Study Completion Date : July 6, 2007

Arm Intervention/treatment
Placebo Comparator: Placebo
Participants were randomized to receive a single dose of matching placebo administered by subcutaneous or intravenous injection.
Drug: Placebo
Administered subcutaneously or intravenously

Experimental: Romosozumab
Participants were randomized to receive a single dose of romosozumab administered by subcutaneous or intravenous injection. The starting dose was 0.1 mg/kg, with sequential escalation up to 10 mg/kg.
Drug: Romosozumab
Administered subcutaneously or intravenously
Other Names:
  • AMG 785
  • EVENITY™




Primary Outcome Measures :
  1. Number of Participants With Adverse Events [ Time Frame: Adverse events were collected from the first dose of treatment up until day 29 for the 0.1 mg/kg and 0.3 mg/kg SC treatment groups, up to 57 days for the 1 mg/kg and 3 mg/kg IV/SC groups and for up to 85 days for the 5 mg/kg and 10 mg/kg SC/IV groups. ]

    Serious adverse events were any events that were fatal, were life-threatening (placed the participant at immediate risk of death), required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, were congenital anomalies or birth defects, or were other significant medical hazards.

    Relatedness to investigational product was assessed by the investigator by means of the question: "Is there a reasonable possibility that the event may have been caused by the investigational product?'


  2. Number of Participants Who Developed Anti-romosozumab Antibodies [ Time Frame: Day 29 (all participants), day 57 (1, 3, 5, and 10 mg/kg treatment groups only) and at day 85 (5 and 10 mg/kg teatment groups only). ]
    Binding anti-romosozumab antibody titers were assessed using a validated electrochemiluninescence (ECL) immunoassay. The limit of detection for this assay was 3.91 ng/mL of anti-romosozumab antibody in neat serum. Samples found to be positive for binding antibodies were further tested using a validated bioassay to determine if the antibodies were able to neutralize the activity of romosozumab. The limit of detection for this assay was ≥ 0.75 μg/mL.


Secondary Outcome Measures :
  1. Maximum Observed Concentration (Cmax) of Romosozumab [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
  2. Time to Maximum Observed Concentration (Tmax) of Romosozumab [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
  3. Initial Concentration Following IV Administration (C0) of Romosozumab [ Time Frame: Day 1 at the end of infusion ]
  4. Area Under the Serum Concentration-time Curve From Time Zero to Infinity for Romosozumab [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
  5. Apparent Clearance (CL/F) / Clearance (CL) for Romosozumab [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
  6. Half-life Associated With the Beta (Plateau) Phase of Elimination for Romosozumab [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
    The plateau (beta, β) phase half-life (t½,β) was calculated from the natural log of 2 divided by the beta phase rate constant (λβ). λβ for a subject was estimated by linear regression of at least 3 contiguous time points that followed the Cmax and constituted a distinct phase that preceded the terminal phase.

  7. Half-life Associated With the Gamma (Terminal) Phase of Elimination for Romosozumab [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
    The terminal (gamma, γ) phase half-life (t½,γ) was calculated from the natural log of 2 divided by the terminal rate constant (λz).

  8. Maximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP) [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
    Defined as the maximum value postdose.

  9. Time to Maximum Effect of P1NP [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
    Defined as the time to maximum value postdose.

  10. Area Under the Curve From Day 0 to Day 29 (AUC0-29) for P1NP [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
  11. Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for P1NP [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab, ]
  12. Maximum Effect for Serum C-telopeptide (sCTX) [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
    Defined as the minimum value postdose.

  13. Time to Maximum Effect of sCTX [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
    Defined as the time to minimum value postdose.

  14. Area Under the Curve From Day 0 to Day 29 (AUC0-29) for sCTX [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
  15. Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for sCTX [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
  16. Maximum Effect for Osteocalcin [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
    Defined as the maximum value postdose.

  17. Time to Maximum Effect of Osteocalcin [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
    Defined as the time to maximum value postdose.

  18. Area Under the Curve From Day 0 to Day 29 (AUC0-29) for Osteocalcin [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
  19. Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for Osteocalcin [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
  20. Maximum Effect for Bone-specific Alkaline Phosphatase (BSAP) [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
    Defined as the maximum value postdose.

  21. Time to Maximum Effect of BSAP [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
    Defined as the time to maximum value postdose.

  22. Area Under the Curve From Day 0 to Day 29 (AUC0-29) for BSAP [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
  23. Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for BSAP [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
  24. Maximum Effect for Intact Parathyroid Hormone (iPTH) [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
    Defined as the maximum value postdose.

  25. Time to Maximum Effect of iPTH [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
    Defined as the time to maximum value postdose.

  26. Area Under the Curve From Day 0 to Day 29 (AUC0-29) for iPTH [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
  27. Area Under the Curve From Day 0 to the Last Sampling Timepoint (AUC0-t) for iPTH [ Time Frame: Predose up to day 29 for participants receiving 0.1 or 0.3 mg/kg romosozumab, up to day 57 for participants receiving 1 or 3 mg/kg romosozumab, and up to day 85 for participants receiving 5 or 10 mg/kg romosozumab. ]
  28. Percent Change From Baseline in Sclerostin [ Time Frame: Baseline and days 15, 29, 43, 57, 71, and 85 ]
  29. Serum Calcium Over Time [ Time Frame: Dday 1 predose and at 4, 6, 8, 10, and 12 hours, days 2, 3, 4, 5, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85 ]
  30. Ionized Calcium Over Time [ Time Frame: Day 1 predose and at 4, 6, 8, 10, 12 hours, days 2, 3, 4, 5, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   45 Years to 59 Years   (Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01059435


Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen

Additional Information:
Publications:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01059435     History of Changes
Other Study ID Numbers: 20060220
First Posted: February 1, 2010    Key Record Dates
Results First Posted: July 4, 2019
Last Update Posted: July 4, 2019
Last Verified: July 2019
Keywords provided by Amgen:
Amgen
First in Human
Postmenopausal
Phase 1
Additional relevant MeSH terms:
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Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs