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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01825785
Recruitment Status : Completed
First Posted : April 8, 2013
Results First Posted : July 5, 2019
Last Update Posted : July 5, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Tracking Information
First Submitted Date  ICMJE January 25, 2013
First Posted Date  ICMJE April 8, 2013
Results First Submitted Date  ICMJE April 10, 2019
Results First Posted Date  ICMJE July 5, 2019
Last Update Posted Date July 5, 2019
Actual Study Start Date  ICMJE November 14, 2007
Actual Primary Completion Date December 2, 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 10, 2019)
  • 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?'
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 3, 2013)
  • Number (percent) of subjects reporting treatment-emergent adverse events [ Time Frame: 169 days following initial investigational product administration ]
  • Number (percent) of subjects who experienced clinically significant changes in safety laboratory tests, physical examinations, vital signs, or electrocardiograms [ Time Frame: 169 days following initial investigational product administration ]
  • Number (percent) of subjects who developed antibodies to AMG 785 [ Time Frame: 169 days following initial investigational product administration ]
Change History Complete list of historical versions of study NCT01825785 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 10, 2019)
  • 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.
  • 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. ]
  • 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)
  • 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. ]
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • Percent Change From Baseline in Sclerostin [ Time Frame: Baseline and days 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155 and 169 ]
  • Change From Baseline in Ionized Calcium [ Time Frame: Baseline and day 169 (or earlier for participants who discontinued before day 169) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 3, 2013)
  • Area under the serum concentration-time curve (AUC), maximum observed concentration (Cmax), and time of maximum drug concentration (Tmax) [ Time Frame: 169 days following initial investigational product administration ]
  • Bone mineral density as assessed by dual energy X-ray absorptiometry, serum procollagen type 1 N-terminal propeptide, osteocalcin, bone-specific alkaline phosphatase, serum CTX, intact Parathyroid Hormone, serum and ionized calcium, and sclerostin levels [ Time Frame: 169 days following initial investigational product administration ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Romosozumab (AMG 785)
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Postmenopausal
  • Osteopenia
Intervention  ICMJE
  • Drug: Romosozumab
    Administered by subcutaneous injection
    Other Names:
    • AMG 785
    • EVENITY™
  • Drug: Placebo
    Administered by subcutaneous injection
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Participants were randomized to receive matching placebo administered by subcutaneous injection once every 2 weeks (Q2W) or once every 4 weeks (Q4W) for 3 months.
    Intervention: Drug: Placebo
  • Experimental: Romosozumab
    Participants were randomized to receive romosozumab administered by subcutaneous injection at doses of 1 mg/kg Q2W, 2 mg/kg Q4W, 2 mg/kg Q2W, or 3 mg/kg Q4W for 3 months.
    Intervention: Drug: Romosozumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 3, 2013)
48
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 2, 2008
Actual Primary Completion Date December 2, 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE Not Provided
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01825785
Other Study ID Numbers  ICMJE 20060221
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Amgen
Study Sponsor  ICMJE Amgen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MD Amgen
PRS Account Amgen
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP