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OpenTrials
Completed

NCT Number: NCT01825785

A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Romosozumab (AMG 785)

The primary objective of this study was to assess the safety, tolerability, and immunogenicity potential of romosozumab following multiple subcutaneous (SC) administrations in healthy men and postmenopausal women with low bone mass.

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Key information

Conditions

Postmenopausal Bone Diseases Bone Diseases, Metabolic Metabolic Diseases Musculoskeletal Diseases Nutritional and Metabolic Diseases Osteopenia

Age range

45 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Healthy males and females between 45 to 80 years of age
  • Postmenopausal females
  • Low bone mineral density, defined by bone mineral density (BMD) T-scores between -1.0 and -2.5, inclusive, for the lumbar spine [L1-L4] or total evaluable vertebrae [if fewer than L1-L4] or total hip)
  • 25-hydroxyvitamin D ≥ 20 ng/mL
  • Weight ≤ 98 kg (216 lb) and/or height ≤ 196 cm (77 in)

Exclusion criteria

  • Osteoporosis defined by bone mineral density (BMD) T-scores < -2.5 for the lumbar spine (L1-L4) or total evaluable vertebrae (if fewer than L1-L4) or total hip
  • Diagnosed with any condition that would affect bone metabolism
  • Previous exposure to AMG 785

Treatment and study plan

Romosozumab

Drug

Administered by subcutaneous injection

Other names: AMG 785, EVENITY™

Placebo

Drug

Administered by subcutaneous injection

Primary outcomes

  1. Number of Participants With Adverse Events

    Time frame: 169 days

    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 Antibodies to Romosozumab

    Time frame: Blood samples for detection of anti-romosozumab antibodies were collected at day 1 (predose) and days 29 (predose), 57 (predose), 85, 113, 141, and 169.

    All samples were tested for binding anti-romsozumab antibodies using an immunoassay; all antibody-positive samples were further tested in a bioassay to determine if the antibodies were neutralizing.

    Development of antibodies to romosozumab is defined as participants with a negative result at baseline and a positive result at any time postbaseline.

Secondary outcomes

  1. Time to Maximum Observed Concentration (Tmax) of Romosozumab

    Time frame: Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.

    Serum concentrations of romosozumab were measured by a validated enzyme-linked immunosorbent assay; the lower limit of quantification (LLOQ) was 50 ng/mL.

  2. Maximum Observed Concentration (Cmax) of Romosozumab

    Time frame: Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.

  3. Area Under the Concentration-time Curve for the Dosing Interval (AUC0-tau) for Romosozumab

    Time frame: Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.

    Area under the serum romosozumab concentration-time curve from time 0 to tau (tau = 14 days for Q2W dose cohorts and 28 days for Q4W dose cohorts)

  4. Half-life Associated With the Terminal Phase of Elimination (T1/2) for Romosozumab

    Time frame: Q2W dose groups: days 71 (predose) to 169; Q24 dose groups: days 57 (predose) to 169.

  5. Accumulation Ratio (AR) for Romosozumab

    Time frame: Q2W dose groups: First dose on days 1 (predose) to 15 (predose); Last dose on days 71 (predose) to 169. Q4W dose groups: First dose on days 1 (predose) to 29 (predose); Last dose on days 57 (predose) to 169.

    The accumulation ratio (AR) was calculated as the ratio of AUC0-tau after the last dose to AUC0-tau after the first dose.

  6. Percent Change From Baseline in Bone Mineral Density of the Total Spine

    Time frame: Baseline and days 29, 85, 127, and 169

    Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans of the lumbar spine (L1-L4) and assessed by a central lab.

  7. Percent Change From Baseline in Bone Mineral Density at the Total Hip

    Time frame: Baseline and days 29, 85, 127, and 169

    Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.

  8. Percent Change From Baseline in Bone Mineral Density at the Femoral Hip

    Time frame: Baseline and days 29, 85, 127, and 169

    Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.

  9. Percent Change From Baseline in Bone Mineral Density at the Distal One-third Radius

    Time frame: Baseline and days 29, 85, 127, and 169

    Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.

  10. Percent Change From Baseline in Bone Mineral Density at the Total Wrist

    Time frame: Baseline and days 29, 85, 127, and 169

    Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.

  11. Percent Change From Baseline in Bone Mineral Density of the Whole Body

    Time frame: Baseline and days 29, 85, 127, and 169

    Bone mineral density was determined by dual energy X-ray absorptiometry (DXA) scans and assessed by a central lab.

  12. Percent Change From Baseline in Procollagen Type 1 N-terminal Propeptide (P1NP)

    Time frame: Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169

  13. Percent Change From Baseline in Osteocalcin

    Time frame: Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169

  14. Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP)

    Time frame: Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169

  15. Percent Change From Baseline in Serum C-telopeptide (sCTX)

    Time frame: Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169

  16. Percent Change From Baseline in Intact Parathyroid Hormone (iPTH)

    Time frame: Baseline and days 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 (Q2W only), 57, 58 (Q4W only), 60 (Q4W only), 62 (Q4W only), 64, 71, 72 (Q2W only), 74 (Q2W only), 76 (Q2W only), 78, 85, 99, 113, 127, 141, 155 and 169

  17. Percent Change From Baseline in Sclerostin

    Time frame: Baseline and days 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155 and 169

  18. Change From Baseline in Ionized Calcium

    Time frame: Baseline and day 169 (or earlier for participants who discontinued before day 169)

Sponsors and collaborators

Lead sponsor

Amgen

Industry

Registry information

Official study title

A Randomized, Double-blind, Placebo-controlled, Ascending Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 785 in Healthy Men and Postmenopausal Women With Low Bone Mass

Important dates

Study start
2007
Primary completion
2008
Study completion
2008
First posted
Apr 8, 2013
Registry last updated
Aug 30, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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