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CompletedNCT01059435Updated Jul 5, 2019Results posted

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

A Phase 1 interventional study of Romosozumab and Placebo in Osteopenia, sponsored by Amgen. Completed. Open to participants aged 45 Years to 59 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-07-05.

Sponsored by Amgen · Phase 1, Interventional, and Treatment

From the registry’s dates

  • Registered 3 years 1 month after the study started (first participant enrolled Dec 2006, registered Jan 2010).
Phase
Phase 1
Study type
Interventional
Enrollment
74
Allocation
Randomized
Ages
45 Years to 59 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Osteopenia

Keywords

  • Amgen
  • First in Human
  • Postmenopausal
  • Phase 1
03

In context

Bone Diseases, Metabolic

470 studies on the registry are indexed under Bone Diseases, Metabolic; 71 are open to participants now.

This study's enrollment of 74 is above the median of 60 across 359 interventional studies indexed under Bone Diseases, Metabolic.

Browse Bone Diseases, Metabolic studies →

Lead sponsor

Amgen is the lead sponsor of 1,015 studies on the registry; 49 are open to participants now.

Of its 245 completed or terminated interventional studies of FDA-regulated products, 159 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
45 Years to 59 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Sequential assignment
Masking
Double (Participant, Investigator)
Enrollment
74 participants (actual)

Study arms

  • Placebo comparator
    Placebo

    Participants were randomized to receive a single dose of matching placebo administered by subcutaneous or intravenous injection.

    Drug: Placebo

  • 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

Interventions

  • DrugRomosozumab

    Administered subcutaneously or intravenously

    Also known as: AMG 785, EVENITY™

  • DrugPlacebo

    Administered subcutaneously or intravenously

06

What researchers measure

Primary outcomes

  1. Number of Participants With Adverse Events

    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?'

    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.

  2. Number of Participants Who Developed Anti-romosozumab Antibodies

    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.

    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).

Secondary outcomes

  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

    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.

    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.

  7. Half-life Associated With the Gamma (Terminal) Phase of Elimination for 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).

    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.

  8. Maximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP)

    Defined as the maximum value postdose.

    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.

  9. Time to Maximum Effect of P1NP

    Defined as the time to maximum value postdose.

    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.

  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)

    Defined as the minimum value postdose.

    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.

  13. Time to Maximum Effect of sCTX

    Defined as the time to minimum value postdose.

    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.

  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

    Defined as the maximum value postdose.

    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.

  17. Time to Maximum Effect of Osteocalcin

    Defined as the time to maximum value postdose.

    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.

  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)

    Defined as the maximum value postdose.

    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.

  21. Time to Maximum Effect of BSAP

    Defined as the time to maximum value postdose.

    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.

  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)

    Defined as the maximum value postdose.

    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.

  25. Time to Maximum Effect of iPTH

    Defined as the time to maximum value postdose.

    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.

  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

07

Results

Posted Jul 5, 2019

Participant flow

This was a single-center study conducted in the USA. The first participant enrolled on 13 December 2006 and the last participant completed the study on 06 July 2007.

Participant flow — Overall Study
MilestonePlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Started14689696466
Received study drug14669696466
Completed14669696466
Not completed0020000000

Outcome measures

PrimaryNumber of Participants With Adverse Events

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?'

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.
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events
ParticipantsPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Any adverse event9441565212
Serious adverse events0000001000
Treatment-related adverse events5420345011
Serious treatment-related adverse events0000001000
Discontinuations due to adverse events0000000000
Deaths0000000000
PrimaryNumber of Participants Who Developed Anti-romosozumab Antibodies

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.

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).
Reported as:
Number · participants
Number of Participants Who Developed Anti-romosozumab Antibodies
participantsPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Binding antibody positive0000022002
Neutralizing antibody positive0000001000
SecondaryMaximum 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.
Reported as:
Mean · ng/mL
Maximum Observed Concentration (Cmax) of Romosozumab
ng/mLRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SC
Maximum Observed Concentration (Cmax) of Romosozumab375 ± 1821280 ± 6534890 ± 178021300 ± 517033500 ± 829075200 ± 15900
SecondaryTime 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.
Reported as:
Median · days
Time to Maximum Observed Concentration (Tmax) of Romosozumab
daysRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SC
Time to Maximum Observed Concentration (Tmax) of Romosozumab1.5 (0.5 to 7)2.5 (2 to 5)3 (2 to 14)5 (4 to 7)5 (3 to 7)4.5 (2 to 7)
SecondaryInitial Concentration Following IV Administration (C0) of Romosozumab
Time frame:
Day 1 at the end of infusion
Reported as:
Mean · ng/mL
Initial Concentration Following IV Administration (C0) of Romosozumab
ng/mLRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Initial Concentration Following IV Administration (C0) of Romosozumab24900 ± 4670132000 ± 13700
SecondaryArea 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.
Reported as:
Mean · µg*hr/mL
Area Under the Serum Concentration-time Curve From Time Zero to Infinity for Romosozumab
µg*hr/mLRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Area Under the Serum Concentration-time Curve From Time Zero to Infinity for Romosozumab78.5 ± 22.6288 ± 1441480 ± 6058170 ± 181016900 ± 435043400 ± 85503020 ± 98924400 ± 4400
SecondaryApparent 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.
Reported as:
Mean · mL/hr/kg
Apparent Clearance (CL/F) / Clearance (CL) for Romosozumab
mL/hr/kgRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Apparent Clearance (CL/F) / Clearance (CL) for Romosozumab1.39 ± 0.4891.35 ± 0.8410.873 ± 0.6470.383 ± 0.09010.319 ± 0.09980.236 ± 0.03700.362 ± 0.1170.210 ± 0.0361
SecondaryHalf-life Associated With the Beta (Plateau) Phase of Elimination for 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.

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.
Reported as:
Mean · days
Half-life Associated With the Beta (Plateau) Phase of Elimination for Romosozumab
daysRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Half-life Associated With the Beta (Plateau) Phase of Elimination for Romosozumab———11.1 ± 3.7012.9 ± 3.1418.0 ± 3.54—10.6 ± 1.70
SecondaryHalf-life Associated With the Gamma (Terminal) Phase of Elimination for 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).

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.
Reported as:
Mean · days
Half-life Associated With the Gamma (Terminal) Phase of Elimination for Romosozumab
daysRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Half-life Associated With the Gamma (Terminal) Phase of Elimination for Romosozumab5.20 ± 1.365.13 ± 0.6405.50 ± 0.3226.68 ± 0.9615.81 ± 0.8745.88 ± 1.604.49 ± 0.9744.93 ± 0.639
SecondaryMaximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP)

Defined as the maximum value postdose.

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.
Reported as:
Mean · ng/mL
Maximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP)
ng/mLPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Maximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP)69.8 ± 32.057.7 ± 22.860.9 ± 14.460.7 ± 10.8100.8 ± 49.6125.1 ± 44.2141.4 ± 24.877.0 ± 35.376.3 ± 19.8173.4 ± 43.3
SecondaryTime to Maximum Effect of P1NP

Defined as the time to maximum value postdose.

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.
Reported as:
Median · days
Time to Maximum Effect of P1NP
daysPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Time to Maximum Effect of P1NP39.5 (1.0 to 64.0)11.0 (6.0 to 29.0)4.5 (1.0 to 15.0)15.0 (11.0 to 57.0)22.0 (15.0 to 22.0)22.0 (15.0 to 29.0)25.5 (22.0 to 36.0)43.0 (1.0 to 57.0)15.0 (11.0 to 22.0)18.5 (15.0 to 29.0)
SecondaryArea 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.
Reported as:
Mean · days*ng/mL
Area Under the Curve From Day 0 to Day 29 (AUC0-29) for P1NP
days*ng/mLPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Area Under the Curve From Day 0 to Day 29 (AUC0-29) for P1NP1529 ± 6331431 ± 5481564 ± 3771473 ± 3042300 ± 10992780 ± 10072986 ± 3061714 ± 7821794 ± 4343940 ± 944
SecondaryArea 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,
Reported as:
Mean · days*ng/mL
Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for P1NP
days*ng/mLPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for P1NP3234 ± 14621431 ± 5481564 ± 3772782 ± 5133962 ± 17026759 ± 24347846 ± 12644487 ± 23523138 ± 7238976 ± 2531
SecondaryMaximum Effect for Serum C-telopeptide (sCTX)

Defined as the minimum value postdose.

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.
Reported as:
Mean · ng/mL
Maximum Effect for Serum C-telopeptide (sCTX)
ng/mLPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Maximum Effect for Serum C-telopeptide (sCTX)0.3 ± 0.20.4 ± 0.20.3 ± 0.10.3 ± 0.10.4 ± 0.10.2 ± 0.10.2 ± 0.10.3 ± 0.20.2 ± 0.10.2 ± 0.1
SecondaryTime to Maximum Effect of sCTX

Defined as the time to minimum value postdose.

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.
Reported as:
Median · days
Time to Maximum Effect of sCTX
daysPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Time to Maximum Effect of sCTX1.0 (1.0 to 36.0)1.0 (1.0 to 1.0)1.0 (1.0 to 1.0)1.0 (1.0 to 43.0)1.0 (1.0 to 50.0)8.0 (1.0 to 78.0)6.0 (1.0 to 22.0)18.5 (1.0 to 43.0)1.0 (1.0 to 1.0)1.0 (1.0 to 64.0)
SecondaryArea 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.
Reported as:
Mean · days*ng/mL
Area Under the Curve From Day 0 to Day 29 (AUC0-29) for sCTX
days*ng/mLPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Area Under the Curve From Day 0 to Day 29 (AUC0-29) for sCTX20 ± 821 ± 618 ± 515 ± 614 ± 311 ± 48 ± 321 ± 813 ± 312 ± 5
SecondaryArea 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.
Reported as:
Mean · days*ng/mL
Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for sCTX
days*ng/mLPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for sCTX37 ± 1821 ± 618 ± 530 ± 1329 ± 741 ± 1840 ± 1544 ± 2026 ± 644 ± 13
SecondaryMaximum Effect for Osteocalcin

Defined as the maximum value postdose.

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.
Reported as:
Mean · µg/L
Maximum Effect for Osteocalcin
µg/LPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Maximum Effect for Osteocalcin28.9 ± 8.125.6 ± 8.025.8 ± 4.826.6 ± 5.536.9 ± 10.939.0 ± 12.753.9 ± 10.535.9 ± 13.928.8 ± 7.753.5 ± 12.8
SecondaryTime to Maximum Effect of Osteocalcin

Defined as the time to maximum value postdose.

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.
Reported as:
Median · days
Time to Maximum Effect of Osteocalcin
daysPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Time to Maximum Effect of Osteocalcin29.0 (2.0 to 57.0)15.0 (2.0 to 15.0)18.5 (2.0 to 38.0)22.0 (11.0 to 36.0)22.0 (22.0 to 29.0)29.0 (29.0 to 50.0)36.0 (26.0 to 57.0)34.0 (5.0 to 64.0)22.0 (11.0 to 36.0)32.5 (29.0 to 43.0)
SecondaryArea 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.
Reported as:
Mean · days*µg/L
Area Under the Curve From Day 0 to Day 29 (AUC0-29) for Osteocalcin
days*µg/LPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Area Under the Curve From Day 0 to Day 29 (AUC0-29) for Osteocalcin617 ± 209611 ± 191658 ± 153570 ± 139753 ± 234757 ± 225881 ± 162759 ± 286559 ± 73973 ± 212
SecondaryArea 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.
Reported as:
Mean · days*µg/L
Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for Osteocalcin
days*µg/LPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for Osteocalcin1259 ± 505611 ± 191658 ± 1531129 ± 2561487 ± 4532470 ± 8272964 ± 5631897 ± 5191132 ± 1312988 ± 460
SecondaryMaximum Effect for Bone-specific Alkaline Phosphatase (BSAP)

Defined as the maximum value postdose.

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.
Reported as:
Mean · µg/L
Maximum Effect for Bone-specific Alkaline Phosphatase (BSAP)
µg/LPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Maximum Effect for Bone-specific Alkaline Phosphatase (BSAP)21.0 ± 5.718.0 ± 6.717.2 ± 3.217.7 ± 4.726.1 ± 7.824.6 ± 8.629.9 ± 8.219.6 ± 3.715.9 ± 4.536.4 ± 15.9
SecondaryTime to Maximum Effect of BSAP

Defined as the time to maximum value postdose.

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.
Reported as:
Median · days
Time to Maximum Effect of BSAP
daysPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Time to Maximum Effect of BSAP36.0 (4.0 to 78.0)16.5 (4.0 to 29.0)13.0 (6.0 to 19.0)15.0 (8.0 to 29.0)22.0 (22.0 to 22.0)22.0 (22.0 to 36.0)22.0 (15.0 to 29.0)46.5 (6.0 to 85.0)13.5 (6.0 to 50.0)29.0 (22.0 to 36.0)
SecondaryArea 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.
Reported as:
Mean · days*µg/L
Area Under the Curve From Day 0 to Day 29 (AUC0-29) for BSAP
days*µg/LPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Area Under the Curve From Day 0 to Day 29 (AUC0-29) for BSAP462 ± 157460 ± 172460 ± 127422 ± 100588 ± 152540 ± 210639 ± 176448 ± 73376 ± 102780 ± 325
SecondaryArea 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.
Reported as:
Mean · days*µg/L
Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for BSAP
days*µg/LPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for BSAP958 ± 428460 ± 172460 ± 127815 ± 1901120 ± 3031496 ± 5271860 ± 5081138 ± 191731 ± 1772033 ± 780
SecondaryMaximum Effect for Intact Parathyroid Hormone (iPTH)

Defined as the maximum value postdose.

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.
Reported as:
Mean · ng/L
Maximum Effect for Intact Parathyroid Hormone (iPTH)
ng/LPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Maximum Effect for Intact Parathyroid Hormone (iPTH)43.3 ± 12.638.7 ± 11.954.5 ± 13.149.9 ± 20.562.8 ± 10.966.0 ± 20.076.3 ± 15.764.8 ± 27.852.7 ± 20.159.7 ± 14.9
SecondaryTime to Maximum Effect of iPTH

Defined as the time to maximum value postdose.

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.
Reported as:
Median · days
Time to Maximum Effect of iPTH
daysPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Time to Maximum Effect of iPTH11.0 (1.0 to 71.0)11.0 (1.0 to 15.0)25.5 (15.0 to 29.0)22.0 (3.0 to 43.0)22.0 (1.0 to 29.0)22.0 (8.0 to 50.0)15.0 (1.0 to 50.0)25.5 (1.0 to 71.0)11.0 (1.0 to 57.0)18.5 (8.0 to 43.0)
SecondaryArea 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.
Reported as:
Mean · days*ng/L
Area Under the Curve From Day 0 to Day 29 (AUC0-29) for iPTH
days*ng/LPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Area Under the Curve From Day 0 to Day 29 (AUC0-29) for iPTH817 ± 295823 ± 2021234 ± 3411002 ± 4051270 ± 1981240 ± 3421422 ± 4111235 ± 4881074 ± 4061239 ± 267
SecondaryArea 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.
Reported as:
Mean · days*ng/L
Area Under the Curve From Day 0 to the Last Sampling Timepoint (AUC0-t) for iPTH
days*ng/LPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Area Under the Curve From Day 0 to the Last Sampling Timepoint (AUC0-t) for iPTH1592 ± 689823 ± 2021234 ± 3411971 ± 8502523 ± 4063483 ± 10574195 ± 11443100 ± 10772072 ± 7493515 ± 1127
SecondaryPercent Change From Baseline in Sclerostin
Time frame:
Baseline and days 15, 29, 43, 57, 71, and 85
Reported as:
Mean · percent change
Percent Change From Baseline in Sclerostin
percent changePlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Day 1553.2 ± 54.3465.5 ± 49.9835.1 ± 130.42123.8 ± 377.67965.9 ± 792.912375.7 ± 1375.417774.8 ± 2444.06.7 ± 11.43776.0 ± 461.514230.0 ± 2428.1
Day 29-8.4 ± 7.0129.0 ± 33.3183.0 ± 19.6717.4 ± 92.45140.2 ± 373.79763.2 ± 1252.818870.9 ± 2707.3-4.3 ± 8.7816.7 ± 222.311715.5 ± 2177.0
Day 43-9.8 ± 14.1——223.2 ± 18.11988.3 ± 339.94968.7 ± 714.713902.7 ± 2381.94.9 ± 8.7196.1 ± 48.74576.0 ± 1086.7
Day 57-3.7 ± 8.6——83.4 ± 14.5810.2 ± 169.92004.9 ± 421.56469.6 ± 1000.315.6 ± 0.649.9 ± 17.41430.0 ± 538.0
Day 7186.9 ± 88.3————610.4 ± 151.62080.8 ± 689.0-5.5 ± 5.4—426.9 ± 119.6
Day 8511.6 ± 16.6————232.1 ± 49.0758.0 ± 270.10.8 ± 13.4—109.8 ± 30.6
SecondarySerum 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
Reported as:
Mean · mg/dL
Serum Calcium Over Time
mg/dLPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Day 1 Pre-dose9.49 ± 0.349.45 ± 0.389.50 ± 0.339.48 ± 0.279.42 ± 0.259.53 ± 0.269.38 ± 0.249.60 ± 0.229.23 ± 0.159.37 ± 0.15
Day 1 Hour 49.46 ± 0.309.62 ± 0.199.45 ± 0.269.38 ± 0.169.38 ± 0.159.59 ± 0.279.35 ± 0.409.45 ± 0.219.43 ± 0.229.40 ± 0.17
Day 1 Hour 69.49 ± 0.269.38 ± 0.229.50 ± 0.149.47 ± 0.179.60 ± 0.249.48 ± 0.359.25 ± 0.369.18 ± 0.139.38 ± 0.319.40 ± 0.15
Day 1 Hour 89.38 ± 0.229.47 ± 0.299.33 ± 0.239.29 ± 0.189.28 ± 0.129.42 ± 0.289.27 ± 0.339.38 ± 0.219.35 ± 0.109.22 ± 0.12
Day 1 Hour 109.53 ± 0.269.62 ± 0.319.50 ± 0.279.40 ± 0.309.38 ± 0.199.36 ± 0.319.28 ± 0.279.50 ± 0.229.45 ± 0.169.42 ± 0.15
Day 1 Hour 129.53 ± 0.289.55 ± 0.279.57 ± 0.319.49 ± 0.319.37 ± 0.349.52 ± 0.269.27 ± 0.349.40 ± 0.249.47 ± 0.199.45 ± 0.19
Day 29.46 ± 0.349.55 ± 0.219.23 ± 0.289.39 ± 0.219.37 ± 0.339.46 ± 0.299.23 ± 0.298.55 ± 1.779.05 ± 0.419.28 ± 0.15
Day 39.30 ± 0.619.37 ± 0.299.25 ± 0.399.20 ± 0.349.35 ± 0.149.38 ± 0.419.18 ± 0.179.40 ± 0.249.13 ± 0.519.27 ± 0.18
Day 49.49 ± 0.259.38 ± 0.279.37 ± 0.279.18 ± 0.649.27 ± 0.129.40 ± 0.309.13 ± 0.229.23 ± 0.508.88 ± 0.849.18 ± 0.13
Day 59.42 ± 0.369.38 ± 0.219.37 ± 0.259.38 ± 0.249.32 ± 0.259.24 ± 0.269.15 ± 0.189.55 ± 0.179.20 ± 0.159.12 ± 0.19
Day 69.56 ± 0.269.45 ± 0.299.45 ± 0.269.51 ± 0.209.35 ± 0.109.36 ± 0.269.18 ± 0.159.35 ± 0.249.32 ± 0.199.23 ± 0.12
Day 89.41 ± 0.319.45 ± 0.209.28 ± 0.239.36 ± 0.449.23 ± 0.109.33 ± 0.408.93 ± 0.289.30 ± 0.229.18 ± 0.299.20 ± 0.37
Day 119.32 ± 0.299.38 ± 0.339.07 ± 0.249.39 ± 0.259.30 ± 0.399.19 ± 0.368.70 ± 0.759.30 ± 0.229.13 ± 0.299.18 ± 0.26
Day 159.39 ± 0.269.60 ± 0.179.40 ± 0.329.26 ± 0.219.22 ± 0.199.06 ± 0.358.97 ± 0.189.33 ± 0.229.28 ± 0.339.00 ± 0.36
Day 229.35 ± 0.339.53 ± 0.459.18 ± 0.359.33 ± 0.329.22 ± 0.179.14 ± 0.478.90 ± 0.239.48 ± 0.139.18 ± 0.229.08 ± 0.15
Day 299.49 ± 0.329.58 ± 0.229.40 ± 0.269.44 ± 0.379.20 ± 0.279.32 ± 0.288.95 ± 0.199.38 ± 0.139.17 ± 0.219.15 ± 0.23
Day 369.40 ± 0.45——9.33 ± 0.269.23 ± 0.309.00 ± 0.269.07 ± 0.269.25 ± 0.309.18 ± 0.359.00 ± 0.30
Day 439.33 ± 0.39——9.32 ± 0.219.37 ± 0.319.23 ± 0.368.90 ± 0.269.28 ± 0.339.25 ± 0.259.15 ± 0.33
Day 509.35 ± 0.26——9.30 ± 0.419.03 ± 0.219.40 ± 0.348.98 ± 0.199.33 ± 0.339.43 ± 0.509.07 ± 0.23
Day 579.46 ± 0.30——9.47 ± 0.369.35 ± 0.299.18 ± 0.499.28 ± 0.179.33 ± 0.299.25 ± 0.279.02 ± 0.21
Day 649.22 ± 0.15————9.28 ± 0.428.90 ± 0.369.25 ± 0.07—9.18 ± 0.35
Day 719.36 ± 0.18————9.47 ± 0.479.05 ± 0.369.20 ± 0.14—9.20 ± 0.14
Day 789.30 ± 0.24————9.31 ± 0.329.07 ± 0.409.20 ± 0.00—9.12 ± 0.34
Day 859.12 ± 0.08————9.47 ± 0.358.82 ± 0.319.10 ± 0.28—9.05 ± 0.26
SecondaryIonized 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
Reported as:
Mean · mg/dL
Ionized Calcium Over Time
mg/dLPlacebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
Day 1 Pre-dose5.02 ± 0.204.95 ± 0.185.02 ± 0.165.01 ± 0.184.88 ± 0.085.07 ± 0.184.85 ± 0.105.30 ± 0.125.18 ± 0.155.27 ± 0.15
Day 1 Hour 45.06 ± 0.205.02 ± 0.175.10 ± 0.135.11 ± 0.245.03 ± 0.105.12 ± 0.324.95 ± 0.085.40 ± 0.145.35 ± 0.185.40 ± 0.09
Day 1 Hour 64.97 ± 0.194.93 ± 0.104.98 ± 0.104.97 ± 0.214.93 ± 0.085.06 ± 0.244.87 ± 0.125.10 ± 0.145.28 ± 0.155.30 ± 0.09
Day 1 Hour 84.93 ± 0.144.92 ± 0.155.00 ± 0.115.00 ± 0.214.90 ± 0.065.04 ± 0.274.78 ± 0.125.30 ± 0.085.28 ± 0.175.30 ± 0.09
Day 1 Hour 105.06 ± 0.205.00 ± 0.095.05 ± 0.105.11 ± 0.194.95 ± 0.155.07 ± 0.344.88 ± 0.125.30 ± 0.125.32 ± 0.185.38 ± 0.15
Day 1 Hour 125.01 ± 0.184.95 ± 0.085.00 ± 0.155.01 ± 0.204.93 ± 0.165.03 ± 0.304.80 ± 0.115.28 ± 0.225.25 ± 0.105.33 ± 0.08
Day 25.04 ± 0.205.03 ± 0.164.92 ± 0.175.03 ± 0.174.98 ± 0.125.04 ± 0.194.88 ± 0.155.28 ± 0.105.08 ± 0.085.18 ± 0.10
Day 35.06 ± 0.195.00 ± 0.134.97 ± 0.145.00 ± 0.144.95 ± 0.085.12 ± 0.204.85 ± 0.055.28 ± 0.135.17 ± 0.125.25 ± 0.14
Day 45.05 ± 0.174.97 ± 0.154.85 ± 0.165.03 ± 0.104.87 ± 0.125.11 ± 0.204.82 ± 0.085.23 ± 0.175.20 ± 0.095.17 ± 0.14
Day 55.02 ± 0.184.93 ± 0.104.88 ± 0.255.04 ± 0.124.93 ± 0.125.04 ± 0.194.80 ± 0.065.40 ± 0.145.18 ± 0.125.15 ± 0.14
Day 65.02 ± 0.164.91 ± 0.144.97 ± 0.125.06 ± 0.114.88 ± 0.105.02 ± 0.144.80 ± 0.065.23 ± 0.105.23 ± 0.125.05 ± 0.10
Day 85.02 ± 0.174.98 ± 0.084.92 ± 0.105.01 ± 0.244.83 ± 0.104.89 ± 0.185.00 ± 0.145.23 ± 0.175.17 ± 0.125.07 ± 0.19
Day 115.01 ± 0.145.05 ± 0.144.93 ± 0.145.06 ± 0.174.90 ± 0.134.92 ± 0.155.00 ± 0.115.23 ± 0.135.20 ± 0.135.10 ± 0.20
Day 155.05 ± 0.165.10 ± 0.194.92 ± 0.125.02 ± 0.164.83 ± 0.124.98 ± 0.195.00 ± 0.065.20 ± 0.225.25 ± 0.125.07 ± 0.12
Day 225.03 ± 0.175.05 ± 0.184.82 ± 0.124.92 ± 0.164.85 ± 0.085.08 ± 0.175.05 ± 0.085.18 ± 0.245.12 ± 0.155.05 ± 0.21
Day 295.13 ± 0.175.05 ± 0.084.92 ± 0.175.02 ± 0.204.85 ± 0.085.22 ± 0.125.03 ± 0.165.28 ± 0.175.22 ± 0.105.13 ± 0.20
Day 365.16 ± 0.17——4.96 ± 0.145.07 ± 0.165.11 ± 0.184.96 ± 0.165.28 ± 0.135.18 ± 0.105.18 ± 0.15
Day 435.18 ± 0.23——4.99 ± 0.155.22 ± 0.135.26 ± 0.215.02 ± 0.085.23 ± 0.175.30 ± 0.135.18 ± 0.12
Day 505.21 ± 0.19——5.19 ± 0.165.20 ± 0.115.16 ± 0.115.00 ± 0.135.28 ± 0.155.32 ± 0.135.15 ± 0.14
Day 575.26 ± 0.14——5.22 ± 0.145.22 ± 0.105.21 ± 0.155.18 ± 0.135.33 ± 0.175.23 ± 0.085.25 ± 0.15
Day 645.18 ± 0.11————5.22 ± 0.185.13 ± 0.145.15 ± 0.07—5.17 ± 0.14
Day 715.18 ± 0.08————5.38 ± 0.165.12 ± 0.185.30 ± 0.28—5.20 ± 0.13
Day 785.28 ± 0.08————5.30 ± 0.175.15 ± 0.195.15 ± 0.07—5.27 ± 0.15
Day 855.24 ± 0.11————5.36 ± 0.135.13 ± 0.225.20 ± 0.14—5.23 ± 0.14

Adverse events

Collected over 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.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo SC—0/14 (0%)9/14 (64.3%)
Placebo IV—0/4 (0%)2/4 (50%)
Romosozumab 0.1 mg/kg SC—0/6 (0%)4/6 (66.7%)
Romosozumab 0.3 mg/kg SC—0/6 (0%)4/6 (66.7%)
Romosozumab 1.0 mg/kg SC—0/9 (0%)1/9 (11.1%)
Romosozumab 10.0 mg/kg SC—1/6 (16.7%)5/6 (83.3%)
Romosozumab 3.0 mg/kg SC—0/6 (0%)5/6 (83.3%)
Romosozumab 5.0 mg/kg SC—0/9 (0%)6/9 (66.7%)
Romosozumab 1.0 mg/kg IV—0/6 (0%)1/6 (16.7%)
Romosozumab 5.0 mg/kg IV—0/6 (0%)2/6 (33.3%)
Most frequent serious events
Most frequent serious events
EventPlacebo SCPlacebo IVRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 10.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
HEPATITISHepatobiliary disorders0/140/40/60/60/91/60/60/90/60/6
Most frequent other events
Showing 10 of 49
Most frequent other events
EventPlacebo SCPlacebo IVRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 10.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IV
INJECTION SITE ERYTHEMAGeneral disorders0/140/40/61/60/94/62/62/90/60/6
DIARRHOEAGastrointestinal disorders0/140/42/60/60/90/60/60/90/60/6
BACK PAINMusculoskeletal and connective tissue disorders1/140/41/60/60/92/60/61/90/60/6
HEADACHENervous system disorders3/140/41/60/60/92/60/61/91/60/6
CONSTIPATIONGastrointestinal disorders1/141/40/60/60/91/60/62/90/61/6
ESCHERICHIA URINARY TRACT INFECTIONInfections and infestations0/141/40/60/60/90/60/60/90/60/6
URINARY TRACT INFECTIONInfections and infestations0/141/40/60/60/91/60/61/90/60/6
DECREASED APPETITEMetabolism and nutrition disorders0/141/40/60/60/90/60/60/90/60/6
INJECTION SITE HAEMORRHAGEGeneral disorders0/140/40/60/60/91/60/62/90/60/6
MUSCLE SPASMSMusculoskeletal and connective tissue disorders0/140/40/60/60/90/60/62/90/60/6

Baseline characteristics

All treated participants

Age, Continuous
Age, Continuous(years)Placebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IVTotal
SC Dosing52.79 ± 4.1753.00 ± 3.9553.33 ± 3.2052.00 ± 4.6455.00 ± 4.0551.89 ± 2.3252.50 ± 4.32NA ± NANA ± NANA ± NA52.80 ± 3.79
IV DosingNA ± NANA ± NANA ± NANA ± NANA ± NANA ± NANA ± NA52.50 ± 4.4349.33 ± 4.6351.00 ± 3.3550.75 ± 4.06
Sex: Female, Male
Sex: Female, Male(Participants)Placebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IVTotal
Female1266666623356
Male200303023316
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Placebo SCRomosozumab 0.1 mg/kg SCRomosozumab 0.3 mg/kg SCRomosozumab 1.0 mg/kg SCRomosozumab 3.0 mg/kg SCRomosozumab 5.0 mg/kg SCRomosozumab 10.0 mg/kg SCPlacebo IVRomosozumab 1.0 mg/kg IVRomosozumab 5.0 mg/kg IVTotal
White or Caucasian20000012106
Black or African American00000000101
Hispanic or Latino1266969524665
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Study locations

No study locations are listed for this record.

09

References and documents

Publications

  • Padhi D, Jang G, Stouch B, Fang L, Posvar E. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res. 2011 Jan;26(1):19-26. doi: 10.1002/jbmr.173. PubMed 20593411 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 5, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT01059435
Lead sponsor
Amgen
Responsible party
Sponsor
First posted
Feb 1, 2010
Start date
Dec 13, 2006
Primary completion
Jul 6, 2007
Completion
Jul 6, 2007
Results posted
Jul 5, 2019
Last update
Jul 5, 2019

Study contacts

MD
study director · Amgen
View the source record on ClinicalTrials.gov ↗

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