Osteopenia
Conditions
Keywords
Amgen, First in Human, Postmenopausal, Phase 1
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.
Interventions
DRUGRomosozumab
Administered subcutaneously or intravenously
DRUGPlacebo
Administered subcutaneously or intravenously
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
45 Years to 59 Years
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | 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?' |
| Number of Participants Who Developed Anti-romosozumab Antibodies | 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
| Measure | Time frame | Description |
|---|---|---|
| Initial Concentration Following IV Administration (C0) of Romosozumab | Day 1 at the end of infusion | — |
| Area Under the Serum Concentration-time Curve From Time Zero to Infinity for Romosozumab | 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. | — |
| Apparent Clearance (CL/F) / Clearance (CL) for Romosozumab | 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. | — |
| Half-life Associated With the Beta (Plateau) Phase of Elimination for Romosozumab | 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. |
| Half-life Associated With the Gamma (Terminal) Phase of Elimination for Romosozumab | 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). |
| Maximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP) | 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. |
| Time to Maximum Effect of P1NP | 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. |
| Area Under the Curve From Day 0 to Day 29 (AUC0-29) for P1NP | 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. | — |
| Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for P1NP | 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, | — |
| Maximum Effect for Serum C-telopeptide (sCTX) | 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. |
| Time to Maximum Effect of sCTX | 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. |
| Area Under the Curve From Day 0 to Day 29 (AUC0-29) for sCTX | 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. | — |
| Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for sCTX | 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. | — |
| Maximum Effect for Osteocalcin | 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. |
| Maximum Observed Concentration (Cmax) of Romosozumab | 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. | — |
| Area Under the Curve From Day 0 to Day 29 (AUC0-29) for Osteocalcin | 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. | — |
| Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for Osteocalcin | 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. | — |
| Maximum Effect for Bone-specific Alkaline Phosphatase (BSAP) | 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. |
| Time to Maximum Effect of BSAP | 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. |
| Area Under the Curve From Day 0 to Day 29 (AUC0-29) for BSAP | 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. | — |
| Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for BSAP | 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. | — |
| Maximum Effect for Intact Parathyroid Hormone (iPTH) | 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. |
| Time to Maximum Effect of iPTH | 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. |
| Area Under the Curve From Day 0 to Day 29 (AUC0-29) for iPTH | 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. | — |
| Area Under the Curve From Day 0 to the Last Sampling Timepoint (AUC0-t) for iPTH | 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. | — |
| Percent Change From Baseline in Sclerostin | Baseline and days 15, 29, 43, 57, 71, and 85 | — |
| Serum Calcium Over Time | 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 | — |
| Ionized Calcium Over Time | 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 | — |
| Time to Maximum Effect of Osteocalcin | 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. |
| Time to Maximum Observed Concentration (Tmax) of Romosozumab | 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. | — |
Participant flow
Recruitment details
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.
Pre-assignment details
Participants were enrolled sequentially into 1 of 6 dose cohorts. Healthy postmenopausal women were randomized to romosozumab or placebo in a 3:1 ratio at 0.1, 0.3, 1 mg/kg SC, 1 mg/kg IV, 3, 5 mg/kg SC, 10 mg/kg SC, or 10 mg/kg IV; healthy men received romosozumab SC or IV, placebo SC or IV in a 3:3:1:1 ratio at doses of 1 mg/kg or 10 mg/kg.
Participants by arm
| Arm | Count |
|---|---|
| Placebo SC Participants received a single subcutaneous (SC) injection of matching placebo. | 14 |
| Romosozumab 0.1 mg/kg SC Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab. | 6 |
| Romosozumab 0.3 mg/kg SC Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab. | 6 |
| Romosozumab 1.0 mg/kg SC Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab. | 9 |
| Romosozumab 3.0 mg/kg SC Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab. | 6 |
| Romosozumab 5.0 mg/kg SC Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab. | 9 |
| Romosozumab 10.0 mg/kg SC Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab. | 6 |
| Placebo IV Participants received a single intravenous (IV) injection of matching placebo. | 4 |
| Romosozumab 1.0 mg/kg IV Participants received a single intravenous injection of 1.0 mg/kg romosozumab. | 6 |
| Romosozumab 5.0 mg/kg IV Participants received a single intravenous injection of 5.0 mg/kg romosozumab | 6 |
| Total | 72 |
Baseline characteristics
| Characteristic | Total | Placebo SC | Romosozumab 0.1 mg/kg SC | Romosozumab 0.3 mg/kg SC | Romosozumab 1.0 mg/kg SC | Romosozumab 3.0 mg/kg SC | Romosozumab 5.0 mg/kg SC | Romosozumab 10.0 mg/kg SC | Placebo IV | Romosozumab 1.0 mg/kg IV | Romosozumab 5.0 mg/kg IV |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous IV Dosing | 50.75 years STANDARD_DEVIATION 4.06 | NA years | NA years | NA years | NA years | NA years | NA years | NA years | 52.50 years STANDARD_DEVIATION 4.43 | 49.33 years STANDARD_DEVIATION 4.63 | 51.00 years STANDARD_DEVIATION 3.35 |
| Age, Continuous SC Dosing | 52.80 years STANDARD_DEVIATION 3.79 | 52.79 years STANDARD_DEVIATION 4.17 | 53.00 years STANDARD_DEVIATION 3.95 | 53.33 years STANDARD_DEVIATION 3.2 | 52.00 years STANDARD_DEVIATION 4.64 | 55.00 years STANDARD_DEVIATION 4.05 | 51.89 years STANDARD_DEVIATION 2.32 | 52.50 years STANDARD_DEVIATION 4.32 | NA years | NA years | NA years |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 65 Participants | 12 Participants | 6 Participants | 6 Participants | 9 Participants | 6 Participants | 9 Participants | 5 Participants | 2 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized White or Caucasian | 6 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Female | 56 Participants | 12 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 2 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 16 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 3 Participants | 0 Participants | 2 Participants | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 14 | 2 / 4 | 4 / 6 | 4 / 6 | 1 / 9 | 5 / 6 | 5 / 6 | 6 / 9 | 1 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 14 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 9 | 1 / 6 | 0 / 6 | 0 / 9 | 0 / 6 | 0 / 6 |
Outcome results
Primary
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).
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo SC | Number of Participants Who Developed Anti-romosozumab Antibodies | Binding antibody positive | 0 participants |
| Placebo SC | Number of Participants Who Developed Anti-romosozumab Antibodies | Neutralizing antibody positive | 0 participants |
| Romosozumab 0.1 mg/kg SC | Number of Participants Who Developed Anti-romosozumab Antibodies | Binding antibody positive | 0 participants |
| Romosozumab 0.1 mg/kg SC | Number of Participants Who Developed Anti-romosozumab Antibodies | Neutralizing antibody positive | 0 participants |
| Romosozumab 0.3 mg/kg SC | Number of Participants Who Developed Anti-romosozumab Antibodies | Binding antibody positive | 0 participants |
| Romosozumab 0.3 mg/kg SC | Number of Participants Who Developed Anti-romosozumab Antibodies | Neutralizing antibody positive | 0 participants |
| Romosozumab 1.0 mg/kg SC | Number of Participants Who Developed Anti-romosozumab Antibodies | Binding antibody positive | 0 participants |
| Romosozumab 1.0 mg/kg SC | Number of Participants Who Developed Anti-romosozumab Antibodies | Neutralizing antibody positive | 0 participants |
| Romosozumab 3.0 mg/kg SC | Number of Participants Who Developed Anti-romosozumab Antibodies | Neutralizing antibody positive | 0 participants |
| Romosozumab 3.0 mg/kg SC | Number of Participants Who Developed Anti-romosozumab Antibodies | Binding antibody positive | 0 participants |
| Romosozumab 5.0 mg/kg SC | Number of Participants Who Developed Anti-romosozumab Antibodies | Neutralizing antibody positive | 0 participants |
| Romosozumab 5.0 mg/kg SC | Number of Participants Who Developed Anti-romosozumab Antibodies | Binding antibody positive | 2 participants |
| Romosozumab 10.0 mg/kg SC | Number of Participants Who Developed Anti-romosozumab Antibodies | Neutralizing antibody positive | 1 participants |
| Romosozumab 10.0 mg/kg SC | Number of Participants Who Developed Anti-romosozumab Antibodies | Binding antibody positive | 2 participants |
| Placebo IV | Number of Participants Who Developed Anti-romosozumab Antibodies | Binding antibody positive | 0 participants |
| Placebo IV | Number of Participants Who Developed Anti-romosozumab Antibodies | Neutralizing antibody positive | 0 participants |
| Romosozumab 1.0 mg/kg IV | Number of Participants Who Developed Anti-romosozumab Antibodies | Binding antibody positive | 0 participants |
| Romosozumab 1.0 mg/kg IV | Number of Participants Who Developed Anti-romosozumab Antibodies | Neutralizing antibody positive | 0 participants |
| Romosozumab 5.0 mg/kg IV | Number of Participants Who Developed Anti-romosozumab Antibodies | Binding antibody positive | 2 participants |
| Romosozumab 5.0 mg/kg IV | Number of Participants Who Developed Anti-romosozumab Antibodies | Neutralizing antibody positive | 0 participants |
Primary
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.
Population: All treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo SC | Number of Participants With Adverse Events | Any adverse event | 9 Participants |
| Placebo SC | Number of Participants With Adverse Events | Treatment-related adverse events | 5 Participants |
| Placebo SC | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Placebo SC | Number of Participants With Adverse Events | Discontinuations due to adverse events | 0 Participants |
| Placebo SC | Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
| Placebo SC | Number of Participants With Adverse Events | Serious treatment-related adverse events | 0 Participants |
| Romosozumab 0.1 mg/kg SC | Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
| Romosozumab 0.1 mg/kg SC | Number of Participants With Adverse Events | Discontinuations due to adverse events | 0 Participants |
| Romosozumab 0.1 mg/kg SC | Number of Participants With Adverse Events | Treatment-related adverse events | 4 Participants |
| Romosozumab 0.1 mg/kg SC | Number of Participants With Adverse Events | Any adverse event | 4 Participants |
| Romosozumab 0.1 mg/kg SC | Number of Participants With Adverse Events | Serious treatment-related adverse events | 0 Participants |
| Romosozumab 0.1 mg/kg SC | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Romosozumab 0.3 mg/kg SC | Number of Participants With Adverse Events | Any adverse event | 4 Participants |
| Romosozumab 0.3 mg/kg SC | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Romosozumab 0.3 mg/kg SC | Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
| Romosozumab 0.3 mg/kg SC | Number of Participants With Adverse Events | Discontinuations due to adverse events | 0 Participants |
| Romosozumab 0.3 mg/kg SC | Number of Participants With Adverse Events | Serious treatment-related adverse events | 0 Participants |
| Romosozumab 0.3 mg/kg SC | Number of Participants With Adverse Events | Treatment-related adverse events | 2 Participants |
| Romosozumab 1.0 mg/kg SC | Number of Participants With Adverse Events | Serious treatment-related adverse events | 0 Participants |
| Romosozumab 1.0 mg/kg SC | Number of Participants With Adverse Events | Treatment-related adverse events | 0 Participants |
| Romosozumab 1.0 mg/kg SC | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Romosozumab 1.0 mg/kg SC | Number of Participants With Adverse Events | Any adverse event | 1 Participants |
| Romosozumab 1.0 mg/kg SC | Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
| Romosozumab 1.0 mg/kg SC | Number of Participants With Adverse Events | Discontinuations due to adverse events | 0 Participants |
| Romosozumab 3.0 mg/kg SC | Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
| Romosozumab 3.0 mg/kg SC | Number of Participants With Adverse Events | Any adverse event | 5 Participants |
| Romosozumab 3.0 mg/kg SC | Number of Participants With Adverse Events | Treatment-related adverse events | 3 Participants |
| Romosozumab 3.0 mg/kg SC | Number of Participants With Adverse Events | Serious treatment-related adverse events | 0 Participants |
| Romosozumab 3.0 mg/kg SC | Number of Participants With Adverse Events | Discontinuations due to adverse events | 0 Participants |
| Romosozumab 3.0 mg/kg SC | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Romosozumab 5.0 mg/kg SC | Number of Participants With Adverse Events | Treatment-related adverse events | 4 Participants |
| Romosozumab 5.0 mg/kg SC | Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
| Romosozumab 5.0 mg/kg SC | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Romosozumab 5.0 mg/kg SC | Number of Participants With Adverse Events | Any adverse event | 6 Participants |
| Romosozumab 5.0 mg/kg SC | Number of Participants With Adverse Events | Discontinuations due to adverse events | 0 Participants |
| Romosozumab 5.0 mg/kg SC | Number of Participants With Adverse Events | Serious treatment-related adverse events | 0 Participants |
| Romosozumab 10.0 mg/kg SC | Number of Participants With Adverse Events | Treatment-related adverse events | 5 Participants |
| Romosozumab 10.0 mg/kg SC | Number of Participants With Adverse Events | Serious treatment-related adverse events | 1 Participants |
| Romosozumab 10.0 mg/kg SC | Number of Participants With Adverse Events | Serious adverse events | 1 Participants |
| Romosozumab 10.0 mg/kg SC | Number of Participants With Adverse Events | Discontinuations due to adverse events | 0 Participants |
| Romosozumab 10.0 mg/kg SC | Number of Participants With Adverse Events | Any adverse event | 5 Participants |
| Romosozumab 10.0 mg/kg SC | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Placebo IV | Number of Participants With Adverse Events | Serious treatment-related adverse events | 0 Participants |
| Placebo IV | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Placebo IV | Number of Participants With Adverse Events | Treatment-related adverse events | 0 Participants |
| Placebo IV | Number of Participants With Adverse Events | Discontinuations due to adverse events | 0 Participants |
| Placebo IV | Number of Participants With Adverse Events | Any adverse event | 2 Participants |
| Placebo IV | Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
| Romosozumab 1.0 mg/kg IV | Number of Participants With Adverse Events | Any adverse event | 1 Participants |
| Romosozumab 1.0 mg/kg IV | Number of Participants With Adverse Events | Treatment-related adverse events | 1 Participants |
| Romosozumab 1.0 mg/kg IV | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Romosozumab 1.0 mg/kg IV | Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
| Romosozumab 1.0 mg/kg IV | Number of Participants With Adverse Events | Serious treatment-related adverse events | 0 Participants |
| Romosozumab 1.0 mg/kg IV | Number of Participants With Adverse Events | Discontinuations due to adverse events | 0 Participants |
| Romosozumab 5.0 mg/kg IV | Number of Participants With Adverse Events | Serious treatment-related adverse events | 0 Participants |
| Romosozumab 5.0 mg/kg IV | Number of Participants With Adverse Events | Discontinuations due to adverse events | 0 Participants |
| Romosozumab 5.0 mg/kg IV | Number of Participants With Adverse Events | Treatment-related adverse events | 1 Participants |
| Romosozumab 5.0 mg/kg IV | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Romosozumab 5.0 mg/kg IV | Number of Participants With Adverse Events | Any adverse event | 2 Participants |
| Romosozumab 5.0 mg/kg IV | Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
Secondary
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.
Population: All treated participants who received romosozumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Apparent Clearance (CL/F) / Clearance (CL) for Romosozumab | 1.39 mL/hr/kg | Standard Deviation 0.489 |
| Romosozumab 0.1 mg/kg SC | Apparent Clearance (CL/F) / Clearance (CL) for Romosozumab | 1.35 mL/hr/kg | Standard Deviation 0.841 |
| Romosozumab 0.3 mg/kg SC | Apparent Clearance (CL/F) / Clearance (CL) for Romosozumab | 0.873 mL/hr/kg | Standard Deviation 0.647 |
| Romosozumab 1.0 mg/kg SC | Apparent Clearance (CL/F) / Clearance (CL) for Romosozumab | 0.383 mL/hr/kg | Standard Deviation 0.0901 |
| Romosozumab 3.0 mg/kg SC | Apparent Clearance (CL/F) / Clearance (CL) for Romosozumab | 0.319 mL/hr/kg | Standard Deviation 0.0998 |
| Romosozumab 5.0 mg/kg SC | Apparent Clearance (CL/F) / Clearance (CL) for Romosozumab | 0.236 mL/hr/kg | Standard Deviation 0.037 |
| Romosozumab 10.0 mg/kg SC | Apparent Clearance (CL/F) / Clearance (CL) for Romosozumab | 0.362 mL/hr/kg | Standard Deviation 0.117 |
| Placebo IV | Apparent Clearance (CL/F) / Clearance (CL) for Romosozumab | 0.210 mL/hr/kg | Standard Deviation 0.0361 |
Secondary
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.
Population: All treated participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for BSAP | 462 days*µg/L | Standard Deviation 157 |
| Romosozumab 0.1 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for BSAP | 460 days*µg/L | Standard Deviation 172 |
| Romosozumab 0.3 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for BSAP | 460 days*µg/L | Standard Deviation 127 |
| Romosozumab 1.0 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for BSAP | 422 days*µg/L | Standard Deviation 100 |
| Romosozumab 3.0 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for BSAP | 588 days*µg/L | Standard Deviation 152 |
| Romosozumab 5.0 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for BSAP | 540 days*µg/L | Standard Deviation 210 |
| Romosozumab 10.0 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for BSAP | 639 days*µg/L | Standard Deviation 176 |
| Placebo IV | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for BSAP | 448 days*µg/L | Standard Deviation 73 |
| Romosozumab 1.0 mg/kg IV | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for BSAP | 376 days*µg/L | Standard Deviation 102 |
| Romosozumab 5.0 mg/kg IV | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for BSAP | 780 days*µg/L | Standard Deviation 325 |
Secondary
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.
Population: All treated participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for iPTH | 817 days*ng/L | Standard Deviation 295 |
| Romosozumab 0.1 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for iPTH | 823 days*ng/L | Standard Deviation 202 |
| Romosozumab 0.3 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for iPTH | 1234 days*ng/L | Standard Deviation 341 |
| Romosozumab 1.0 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for iPTH | 1002 days*ng/L | Standard Deviation 405 |
| Romosozumab 3.0 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for iPTH | 1270 days*ng/L | Standard Deviation 198 |
| Romosozumab 5.0 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for iPTH | 1240 days*ng/L | Standard Deviation 342 |
| Romosozumab 10.0 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for iPTH | 1422 days*ng/L | Standard Deviation 411 |
| Placebo IV | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for iPTH | 1235 days*ng/L | Standard Deviation 488 |
| Romosozumab 1.0 mg/kg IV | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for iPTH | 1074 days*ng/L | Standard Deviation 406 |
| Romosozumab 5.0 mg/kg IV | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for iPTH | 1239 days*ng/L | Standard Deviation 267 |
Secondary
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.
Population: All treated participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for Osteocalcin | 617 days*µg/L | Standard Deviation 209 |
| Romosozumab 0.1 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for Osteocalcin | 611 days*µg/L | Standard Deviation 191 |
| Romosozumab 0.3 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for Osteocalcin | 658 days*µg/L | Standard Deviation 153 |
| Romosozumab 1.0 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for Osteocalcin | 570 days*µg/L | Standard Deviation 139 |
| Romosozumab 3.0 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for Osteocalcin | 753 days*µg/L | Standard Deviation 234 |
| Romosozumab 5.0 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for Osteocalcin | 757 days*µg/L | Standard Deviation 225 |
| Romosozumab 10.0 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for Osteocalcin | 881 days*µg/L | Standard Deviation 162 |
| Placebo IV | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for Osteocalcin | 759 days*µg/L | Standard Deviation 286 |
| Romosozumab 1.0 mg/kg IV | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for Osteocalcin | 559 days*µg/L | Standard Deviation 73 |
| Romosozumab 5.0 mg/kg IV | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for Osteocalcin | 973 days*µg/L | Standard Deviation 212 |
Secondary
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.
Population: All treated participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for P1NP | 1529 days*ng/mL | Standard Deviation 633 |
| Romosozumab 0.1 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for P1NP | 1431 days*ng/mL | Standard Deviation 548 |
| Romosozumab 0.3 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for P1NP | 1564 days*ng/mL | Standard Deviation 377 |
| Romosozumab 1.0 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for P1NP | 1473 days*ng/mL | Standard Deviation 304 |
| Romosozumab 3.0 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for P1NP | 2300 days*ng/mL | Standard Deviation 1099 |
| Romosozumab 5.0 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for P1NP | 2780 days*ng/mL | Standard Deviation 1007 |
| Romosozumab 10.0 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for P1NP | 2986 days*ng/mL | Standard Deviation 306 |
| Placebo IV | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for P1NP | 1714 days*ng/mL | Standard Deviation 782 |
| Romosozumab 1.0 mg/kg IV | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for P1NP | 1794 days*ng/mL | Standard Deviation 434 |
| Romosozumab 5.0 mg/kg IV | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for P1NP | 3940 days*ng/mL | Standard Deviation 944 |
Secondary
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.
Population: All treated participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for sCTX | 20 days*ng/mL | Standard Deviation 8 |
| Romosozumab 0.1 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for sCTX | 21 days*ng/mL | Standard Deviation 6 |
| Romosozumab 0.3 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for sCTX | 18 days*ng/mL | Standard Deviation 5 |
| Romosozumab 1.0 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for sCTX | 15 days*ng/mL | Standard Deviation 6 |
| Romosozumab 3.0 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for sCTX | 14 days*ng/mL | Standard Deviation 3 |
| Romosozumab 5.0 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for sCTX | 11 days*ng/mL | Standard Deviation 4 |
| Romosozumab 10.0 mg/kg SC | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for sCTX | 8 days*ng/mL | Standard Deviation 3 |
| Placebo IV | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for sCTX | 21 days*ng/mL | Standard Deviation 8 |
| Romosozumab 1.0 mg/kg IV | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for sCTX | 13 days*ng/mL | Standard Deviation 3 |
| Romosozumab 5.0 mg/kg IV | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for sCTX | 12 days*ng/mL | Standard Deviation 5 |
Secondary
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.
Population: All treated participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for BSAP | 958 days*µg/L | Standard Deviation 428 |
| Romosozumab 0.1 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for BSAP | 460 days*µg/L | Standard Deviation 172 |
| Romosozumab 0.3 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for BSAP | 460 days*µg/L | Standard Deviation 127 |
| Romosozumab 1.0 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for BSAP | 815 days*µg/L | Standard Deviation 190 |
| Romosozumab 3.0 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for BSAP | 1120 days*µg/L | Standard Deviation 303 |
| Romosozumab 5.0 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for BSAP | 1496 days*µg/L | Standard Deviation 527 |
| Romosozumab 10.0 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for BSAP | 1860 days*µg/L | Standard Deviation 508 |
| Placebo IV | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for BSAP | 1138 days*µg/L | Standard Deviation 191 |
| Romosozumab 1.0 mg/kg IV | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for BSAP | 731 days*µg/L | Standard Deviation 177 |
| Romosozumab 5.0 mg/kg IV | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for BSAP | 2033 days*µg/L | Standard Deviation 780 |
Secondary
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.
Population: All treated participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Area Under the Curve From Day 0 to the Last Sampling Timepoint (AUC0-t) for iPTH | 1592 days*ng/L | Standard Deviation 689 |
| Romosozumab 0.1 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Timepoint (AUC0-t) for iPTH | 823 days*ng/L | Standard Deviation 202 |
| Romosozumab 0.3 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Timepoint (AUC0-t) for iPTH | 1234 days*ng/L | Standard Deviation 341 |
| Romosozumab 1.0 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Timepoint (AUC0-t) for iPTH | 1971 days*ng/L | Standard Deviation 850 |
| Romosozumab 3.0 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Timepoint (AUC0-t) for iPTH | 2523 days*ng/L | Standard Deviation 406 |
| Romosozumab 5.0 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Timepoint (AUC0-t) for iPTH | 3483 days*ng/L | Standard Deviation 1057 |
| Romosozumab 10.0 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Timepoint (AUC0-t) for iPTH | 4195 days*ng/L | Standard Deviation 1144 |
| Placebo IV | Area Under the Curve From Day 0 to the Last Sampling Timepoint (AUC0-t) for iPTH | 3100 days*ng/L | Standard Deviation 1077 |
| Romosozumab 1.0 mg/kg IV | Area Under the Curve From Day 0 to the Last Sampling Timepoint (AUC0-t) for iPTH | 2072 days*ng/L | Standard Deviation 749 |
| Romosozumab 5.0 mg/kg IV | Area Under the Curve From Day 0 to the Last Sampling Timepoint (AUC0-t) for iPTH | 3515 days*ng/L | Standard Deviation 1127 |
Secondary
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.
Population: All treated participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for Osteocalcin | 1259 days*µg/L | Standard Deviation 505 |
| Romosozumab 0.1 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for Osteocalcin | 611 days*µg/L | Standard Deviation 191 |
| Romosozumab 0.3 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for Osteocalcin | 658 days*µg/L | Standard Deviation 153 |
| Romosozumab 1.0 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for Osteocalcin | 1129 days*µg/L | Standard Deviation 256 |
| Romosozumab 3.0 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for Osteocalcin | 1487 days*µg/L | Standard Deviation 453 |
| Romosozumab 5.0 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for Osteocalcin | 2470 days*µg/L | Standard Deviation 827 |
| Romosozumab 10.0 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for Osteocalcin | 2964 days*µg/L | Standard Deviation 563 |
| Placebo IV | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for Osteocalcin | 1897 days*µg/L | Standard Deviation 519 |
| Romosozumab 1.0 mg/kg IV | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for Osteocalcin | 1132 days*µg/L | Standard Deviation 131 |
| Romosozumab 5.0 mg/kg IV | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for Osteocalcin | 2988 days*µg/L | Standard Deviation 460 |
Secondary
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,
Population: All treated participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for P1NP | 3234 days*ng/mL | Standard Deviation 1462 |
| Romosozumab 0.1 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for P1NP | 1431 days*ng/mL | Standard Deviation 548 |
| Romosozumab 0.3 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for P1NP | 1564 days*ng/mL | Standard Deviation 377 |
| Romosozumab 1.0 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for P1NP | 2782 days*ng/mL | Standard Deviation 513 |
| Romosozumab 3.0 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for P1NP | 3962 days*ng/mL | Standard Deviation 1702 |
| Romosozumab 5.0 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for P1NP | 6759 days*ng/mL | Standard Deviation 2434 |
| Romosozumab 10.0 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for P1NP | 7846 days*ng/mL | Standard Deviation 1264 |
| Placebo IV | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for P1NP | 4487 days*ng/mL | Standard Deviation 2352 |
| Romosozumab 1.0 mg/kg IV | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for P1NP | 3138 days*ng/mL | Standard Deviation 723 |
| Romosozumab 5.0 mg/kg IV | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for P1NP | 8976 days*ng/mL | Standard Deviation 2531 |
Secondary
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.
Population: All treated participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for sCTX | 37 days*ng/mL | Standard Deviation 18 |
| Romosozumab 0.1 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for sCTX | 21 days*ng/mL | Standard Deviation 6 |
| Romosozumab 0.3 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for sCTX | 18 days*ng/mL | Standard Deviation 5 |
| Romosozumab 1.0 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for sCTX | 30 days*ng/mL | Standard Deviation 13 |
| Romosozumab 3.0 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for sCTX | 29 days*ng/mL | Standard Deviation 7 |
| Romosozumab 5.0 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for sCTX | 41 days*ng/mL | Standard Deviation 18 |
| Romosozumab 10.0 mg/kg SC | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for sCTX | 40 days*ng/mL | Standard Deviation 15 |
| Placebo IV | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for sCTX | 44 days*ng/mL | Standard Deviation 20 |
| Romosozumab 1.0 mg/kg IV | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for sCTX | 26 days*ng/mL | Standard Deviation 6 |
| Romosozumab 5.0 mg/kg IV | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for sCTX | 44 days*ng/mL | Standard Deviation 13 |
Secondary
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.
Population: All treated participants who received romosozumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Area Under the Serum Concentration-time Curve From Time Zero to Infinity for Romosozumab | 78.5 µg*hr/mL | Standard Deviation 22.6 |
| Romosozumab 0.1 mg/kg SC | Area Under the Serum Concentration-time Curve From Time Zero to Infinity for Romosozumab | 288 µg*hr/mL | Standard Deviation 144 |
| Romosozumab 0.3 mg/kg SC | Area Under the Serum Concentration-time Curve From Time Zero to Infinity for Romosozumab | 1480 µg*hr/mL | Standard Deviation 605 |
| Romosozumab 1.0 mg/kg SC | Area Under the Serum Concentration-time Curve From Time Zero to Infinity for Romosozumab | 8170 µg*hr/mL | Standard Deviation 1810 |
| Romosozumab 3.0 mg/kg SC | Area Under the Serum Concentration-time Curve From Time Zero to Infinity for Romosozumab | 16900 µg*hr/mL | Standard Deviation 4350 |
| Romosozumab 5.0 mg/kg SC | Area Under the Serum Concentration-time Curve From Time Zero to Infinity for Romosozumab | 43400 µg*hr/mL | Standard Deviation 8550 |
| Romosozumab 10.0 mg/kg SC | Area Under the Serum Concentration-time Curve From Time Zero to Infinity for Romosozumab | 3020 µg*hr/mL | Standard Deviation 989 |
| Placebo IV | Area Under the Serum Concentration-time Curve From Time Zero to Infinity for Romosozumab | 24400 µg*hr/mL | Standard Deviation 4400 |
Secondary
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.
Population: All treated participants who received 3, 5, or 10 mg/kg romosozumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Romosozumab 1.0 mg/kg SC | Half-life Associated With the Beta (Plateau) Phase of Elimination for Romosozumab | 11.1 days | Standard Deviation 3.7 |
| Romosozumab 3.0 mg/kg SC | Half-life Associated With the Beta (Plateau) Phase of Elimination for Romosozumab | 12.9 days | Standard Deviation 3.14 |
| Romosozumab 5.0 mg/kg SC | Half-life Associated With the Beta (Plateau) Phase of Elimination for Romosozumab | 18.0 days | Standard Deviation 3.54 |
| Placebo IV | Half-life Associated With the Beta (Plateau) Phase of Elimination for Romosozumab | 10.6 days | Standard Deviation 1.7 |
Secondary
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.
Population: All treated participants who received romosozumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Half-life Associated With the Gamma (Terminal) Phase of Elimination for Romosozumab | 5.20 days | Standard Deviation 1.36 |
| Romosozumab 0.1 mg/kg SC | Half-life Associated With the Gamma (Terminal) Phase of Elimination for Romosozumab | 5.13 days | Standard Deviation 0.64 |
| Romosozumab 0.3 mg/kg SC | Half-life Associated With the Gamma (Terminal) Phase of Elimination for Romosozumab | 5.50 days | Standard Deviation 0.322 |
| Romosozumab 1.0 mg/kg SC | Half-life Associated With the Gamma (Terminal) Phase of Elimination for Romosozumab | 6.68 days | Standard Deviation 0.961 |
| Romosozumab 3.0 mg/kg SC | Half-life Associated With the Gamma (Terminal) Phase of Elimination for Romosozumab | 5.81 days | Standard Deviation 0.874 |
| Romosozumab 5.0 mg/kg SC | Half-life Associated With the Gamma (Terminal) Phase of Elimination for Romosozumab | 5.88 days | Standard Deviation 1.6 |
| Romosozumab 10.0 mg/kg SC | Half-life Associated With the Gamma (Terminal) Phase of Elimination for Romosozumab | 4.49 days | Standard Deviation 0.974 |
| Placebo IV | Half-life Associated With the Gamma (Terminal) Phase of Elimination for Romosozumab | 4.93 days | Standard Deviation 0.639 |
Secondary
Initial Concentration Following IV Administration (C0) of Romosozumab
Time frame: Day 1 at the end of infusion
Population: All treated participants who received intravenously administered romosozumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Initial Concentration Following IV Administration (C0) of Romosozumab | 24900 ng/mL | Standard Deviation 4670 |
| Romosozumab 0.1 mg/kg SC | Initial Concentration Following IV Administration (C0) of Romosozumab | 132000 ng/mL | Standard Deviation 13700 |
Secondary
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
Population: All treated participants; only participants who received ≥ 1 mg/kg romosozumab/placebo were assessed after day 29 and only participants who received 5 or 10 mg/kg romosozumab/placebo were assessed after day 57.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo SC | Ionized Calcium Over Time | Day 2 | 5.04 mg/dL | Standard Deviation 0.2 |
| Placebo SC | Ionized Calcium Over Time | Day 1 Hour 4 | 5.06 mg/dL | Standard Deviation 0.2 |
| Placebo SC | Ionized Calcium Over Time | Day 36 | 5.16 mg/dL | Standard Deviation 0.17 |
| Placebo SC | Ionized Calcium Over Time | Day 29 | 5.13 mg/dL | Standard Deviation 0.17 |
| Placebo SC | Ionized Calcium Over Time | Day 22 | 5.03 mg/dL | Standard Deviation 0.17 |
| Placebo SC | Ionized Calcium Over Time | Day 15 | 5.05 mg/dL | Standard Deviation 0.16 |
| Placebo SC | Ionized Calcium Over Time | Day 1 Hour 6 | 4.97 mg/dL | Standard Deviation 0.19 |
| Placebo SC | Ionized Calcium Over Time | Day 85 | 5.24 mg/dL | Standard Deviation 0.11 |
| Placebo SC | Ionized Calcium Over Time | Day 11 | 5.01 mg/dL | Standard Deviation 0.14 |
| Placebo SC | Ionized Calcium Over Time | Day 8 | 5.02 mg/dL | Standard Deviation 0.17 |
| Placebo SC | Ionized Calcium Over Time | Day 6 | 5.02 mg/dL | Standard Deviation 0.16 |
| Placebo SC | Ionized Calcium Over Time | Day 1 Hour 8 | 4.93 mg/dL | Standard Deviation 0.14 |
| Placebo SC | Ionized Calcium Over Time | Day 78 | 5.28 mg/dL | Standard Deviation 0.08 |
| Placebo SC | Ionized Calcium Over Time | Day 5 | 5.02 mg/dL | Standard Deviation 0.18 |
| Placebo SC | Ionized Calcium Over Time | Day 4 | 5.05 mg/dL | Standard Deviation 0.17 |
| Placebo SC | Ionized Calcium Over Time | Day 3 | 5.06 mg/dL | Standard Deviation 0.19 |
| Placebo SC | Ionized Calcium Over Time | Day 1 Hour 10 | 5.06 mg/dL | Standard Deviation 0.2 |
| Placebo SC | Ionized Calcium Over Time | Day 71 | 5.18 mg/dL | Standard Deviation 0.08 |
| Placebo SC | Ionized Calcium Over Time | Day 1 Pre-dose | 5.02 mg/dL | Standard Deviation 0.2 |
| Placebo SC | Ionized Calcium Over Time | Day 1 Hour 12 | 5.01 mg/dL | Standard Deviation 0.18 |
| Placebo SC | Ionized Calcium Over Time | Day 64 | 5.18 mg/dL | Standard Deviation 0.11 |
| Placebo SC | Ionized Calcium Over Time | Day 57 | 5.26 mg/dL | Standard Deviation 0.14 |
| Placebo SC | Ionized Calcium Over Time | Day 50 | 5.21 mg/dL | Standard Deviation 0.19 |
| Placebo SC | Ionized Calcium Over Time | Day 43 | 5.18 mg/dL | Standard Deviation 0.23 |
| Romosozumab 0.1 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 10 | 5.00 mg/dL | Standard Deviation 0.09 |
| Romosozumab 0.1 mg/kg SC | Ionized Calcium Over Time | Day 6 | 4.91 mg/dL | Standard Deviation 0.14 |
| Romosozumab 0.1 mg/kg SC | Ionized Calcium Over Time | Day 15 | 5.10 mg/dL | Standard Deviation 0.19 |
| Romosozumab 0.1 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 12 | 4.95 mg/dL | Standard Deviation 0.08 |
| Romosozumab 0.1 mg/kg SC | Ionized Calcium Over Time | Day 3 | 5.00 mg/dL | Standard Deviation 0.13 |
| Romosozumab 0.1 mg/kg SC | Ionized Calcium Over Time | Day 5 | 4.93 mg/dL | Standard Deviation 0.1 |
| Romosozumab 0.1 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 6 | 4.93 mg/dL | Standard Deviation 0.1 |
| Romosozumab 0.1 mg/kg SC | Ionized Calcium Over Time | Day 4 | 4.97 mg/dL | Standard Deviation 0.15 |
| Romosozumab 0.1 mg/kg SC | Ionized Calcium Over Time | Day 11 | 5.05 mg/dL | Standard Deviation 0.14 |
| Romosozumab 0.1 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 8 | 4.92 mg/dL | Standard Deviation 0.15 |
| Romosozumab 0.1 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 4 | 5.02 mg/dL | Standard Deviation 0.17 |
| Romosozumab 0.1 mg/kg SC | Ionized Calcium Over Time | Day 1 Pre-dose | 4.95 mg/dL | Standard Deviation 0.18 |
| Romosozumab 0.1 mg/kg SC | Ionized Calcium Over Time | Day 8 | 4.98 mg/dL | Standard Deviation 0.08 |
| Romosozumab 0.1 mg/kg SC | Ionized Calcium Over Time | Day 29 | 5.05 mg/dL | Standard Deviation 0.08 |
| Romosozumab 0.1 mg/kg SC | Ionized Calcium Over Time | Day 2 | 5.03 mg/dL | Standard Deviation 0.16 |
| Romosozumab 0.1 mg/kg SC | Ionized Calcium Over Time | Day 22 | 5.05 mg/dL | Standard Deviation 0.18 |
| Romosozumab 0.3 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 12 | 5.00 mg/dL | Standard Deviation 0.15 |
| Romosozumab 0.3 mg/kg SC | Ionized Calcium Over Time | Day 1 Pre-dose | 5.02 mg/dL | Standard Deviation 0.16 |
| Romosozumab 0.3 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 4 | 5.10 mg/dL | Standard Deviation 0.13 |
| Romosozumab 0.3 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 6 | 4.98 mg/dL | Standard Deviation 0.1 |
| Romosozumab 0.3 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 8 | 5.00 mg/dL | Standard Deviation 0.11 |
| Romosozumab 0.3 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 10 | 5.05 mg/dL | Standard Deviation 0.1 |
| Romosozumab 0.3 mg/kg SC | Ionized Calcium Over Time | Day 2 | 4.92 mg/dL | Standard Deviation 0.17 |
| Romosozumab 0.3 mg/kg SC | Ionized Calcium Over Time | Day 3 | 4.97 mg/dL | Standard Deviation 0.14 |
| Romosozumab 0.3 mg/kg SC | Ionized Calcium Over Time | Day 4 | 4.85 mg/dL | Standard Deviation 0.16 |
| Romosozumab 0.3 mg/kg SC | Ionized Calcium Over Time | Day 5 | 4.88 mg/dL | Standard Deviation 0.25 |
| Romosozumab 0.3 mg/kg SC | Ionized Calcium Over Time | Day 6 | 4.97 mg/dL | Standard Deviation 0.12 |
| Romosozumab 0.3 mg/kg SC | Ionized Calcium Over Time | Day 8 | 4.92 mg/dL | Standard Deviation 0.1 |
| Romosozumab 0.3 mg/kg SC | Ionized Calcium Over Time | Day 11 | 4.93 mg/dL | Standard Deviation 0.14 |
| Romosozumab 0.3 mg/kg SC | Ionized Calcium Over Time | Day 15 | 4.92 mg/dL | Standard Deviation 0.12 |
| Romosozumab 0.3 mg/kg SC | Ionized Calcium Over Time | Day 22 | 4.82 mg/dL | Standard Deviation 0.12 |
| Romosozumab 0.3 mg/kg SC | Ionized Calcium Over Time | Day 29 | 4.92 mg/dL | Standard Deviation 0.17 |
| Romosozumab 1.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 4 | 5.11 mg/dL | Standard Deviation 0.24 |
| Romosozumab 1.0 mg/kg SC | Ionized Calcium Over Time | Day 57 | 5.22 mg/dL | Standard Deviation 0.14 |
| Romosozumab 1.0 mg/kg SC | Ionized Calcium Over Time | Day 29 | 5.02 mg/dL | Standard Deviation 0.2 |
| Romosozumab 1.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Pre-dose | 5.01 mg/dL | Standard Deviation 0.18 |
| Romosozumab 1.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 10 | 5.11 mg/dL | Standard Deviation 0.19 |
| Romosozumab 1.0 mg/kg SC | Ionized Calcium Over Time | Day 50 | 5.19 mg/dL | Standard Deviation 0.16 |
| Romosozumab 1.0 mg/kg SC | Ionized Calcium Over Time | Day 2 | 5.03 mg/dL | Standard Deviation 0.17 |
| Romosozumab 1.0 mg/kg SC | Ionized Calcium Over Time | Day 4 | 5.03 mg/dL | Standard Deviation 0.1 |
| Romosozumab 1.0 mg/kg SC | Ionized Calcium Over Time | Day 43 | 4.99 mg/dL | Standard Deviation 0.15 |
| Romosozumab 1.0 mg/kg SC | Ionized Calcium Over Time | Day 8 | 5.01 mg/dL | Standard Deviation 0.24 |
| Romosozumab 1.0 mg/kg SC | Ionized Calcium Over Time | Day 22 | 4.92 mg/dL | Standard Deviation 0.16 |
| Romosozumab 1.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 12 | 5.01 mg/dL | Standard Deviation 0.2 |
| Romosozumab 1.0 mg/kg SC | Ionized Calcium Over Time | Day 15 | 5.02 mg/dL | Standard Deviation 0.16 |
| Romosozumab 1.0 mg/kg SC | Ionized Calcium Over Time | Day 3 | 5.00 mg/dL | Standard Deviation 0.14 |
| Romosozumab 1.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 8 | 5.00 mg/dL | Standard Deviation 0.21 |
| Romosozumab 1.0 mg/kg SC | Ionized Calcium Over Time | Day 11 | 5.06 mg/dL | Standard Deviation 0.17 |
| Romosozumab 1.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 6 | 4.97 mg/dL | Standard Deviation 0.21 |
| Romosozumab 1.0 mg/kg SC | Ionized Calcium Over Time | Day 5 | 5.04 mg/dL | Standard Deviation 0.12 |
| Romosozumab 1.0 mg/kg SC | Ionized Calcium Over Time | Day 6 | 5.06 mg/dL | Standard Deviation 0.11 |
| Romosozumab 1.0 mg/kg SC | Ionized Calcium Over Time | Day 36 | 4.96 mg/dL | Standard Deviation 0.14 |
| Romosozumab 3.0 mg/kg SC | Ionized Calcium Over Time | Day 57 | 5.22 mg/dL | Standard Deviation 0.1 |
| Romosozumab 3.0 mg/kg SC | Ionized Calcium Over Time | Day 8 | 4.83 mg/dL | Standard Deviation 0.1 |
| Romosozumab 3.0 mg/kg SC | Ionized Calcium Over Time | Day 6 | 4.88 mg/dL | Standard Deviation 0.1 |
| Romosozumab 3.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Pre-dose | 4.88 mg/dL | Standard Deviation 0.08 |
| Romosozumab 3.0 mg/kg SC | Ionized Calcium Over Time | Day 2 | 4.98 mg/dL | Standard Deviation 0.12 |
| Romosozumab 3.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 12 | 4.93 mg/dL | Standard Deviation 0.16 |
| Romosozumab 3.0 mg/kg SC | Ionized Calcium Over Time | Day 50 | 5.20 mg/dL | Standard Deviation 0.11 |
| Romosozumab 3.0 mg/kg SC | Ionized Calcium Over Time | Day 43 | 5.22 mg/dL | Standard Deviation 0.13 |
| Romosozumab 3.0 mg/kg SC | Ionized Calcium Over Time | Day 36 | 5.07 mg/dL | Standard Deviation 0.16 |
| Romosozumab 3.0 mg/kg SC | Ionized Calcium Over Time | Day 3 | 4.95 mg/dL | Standard Deviation 0.08 |
| Romosozumab 3.0 mg/kg SC | Ionized Calcium Over Time | Day 29 | 4.85 mg/dL | Standard Deviation 0.08 |
| Romosozumab 3.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 4 | 5.03 mg/dL | Standard Deviation 0.1 |
| Romosozumab 3.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 8 | 4.90 mg/dL | Standard Deviation 0.06 |
| Romosozumab 3.0 mg/kg SC | Ionized Calcium Over Time | Day 22 | 4.85 mg/dL | Standard Deviation 0.08 |
| Romosozumab 3.0 mg/kg SC | Ionized Calcium Over Time | Day 4 | 4.87 mg/dL | Standard Deviation 0.12 |
| Romosozumab 3.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 10 | 4.95 mg/dL | Standard Deviation 0.15 |
| Romosozumab 3.0 mg/kg SC | Ionized Calcium Over Time | Day 15 | 4.83 mg/dL | Standard Deviation 0.12 |
| Romosozumab 3.0 mg/kg SC | Ionized Calcium Over Time | Day 11 | 4.90 mg/dL | Standard Deviation 0.13 |
| Romosozumab 3.0 mg/kg SC | Ionized Calcium Over Time | Day 5 | 4.93 mg/dL | Standard Deviation 0.12 |
| Romosozumab 3.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 6 | 4.93 mg/dL | Standard Deviation 0.08 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 3 | 5.12 mg/dL | Standard Deviation 0.2 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 2 | 5.04 mg/dL | Standard Deviation 0.19 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 78 | 5.30 mg/dL | Standard Deviation 0.17 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 8 | 5.04 mg/dL | Standard Deviation 0.27 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 4 | 5.11 mg/dL | Standard Deviation 0.2 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 5 | 5.04 mg/dL | Standard Deviation 0.19 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 6 | 5.02 mg/dL | Standard Deviation 0.14 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 6 | 5.06 mg/dL | Standard Deviation 0.24 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 8 | 4.89 mg/dL | Standard Deviation 0.18 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 85 | 5.36 mg/dL | Standard Deviation 0.13 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 11 | 4.92 mg/dL | Standard Deviation 0.15 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 15 | 4.98 mg/dL | Standard Deviation 0.19 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 22 | 5.08 mg/dL | Standard Deviation 0.17 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 4 | 5.12 mg/dL | Standard Deviation 0.32 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 29 | 5.22 mg/dL | Standard Deviation 0.12 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 36 | 5.11 mg/dL | Standard Deviation 0.18 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 43 | 5.26 mg/dL | Standard Deviation 0.21 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 50 | 5.16 mg/dL | Standard Deviation 0.11 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 57 | 5.21 mg/dL | Standard Deviation 0.15 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 64 | 5.22 mg/dL | Standard Deviation 0.18 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Pre-dose | 5.07 mg/dL | Standard Deviation 0.18 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 71 | 5.38 mg/dL | Standard Deviation 0.16 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 10 | 5.07 mg/dL | Standard Deviation 0.34 |
| Romosozumab 5.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 12 | 5.03 mg/dL | Standard Deviation 0.3 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 4 | 4.82 mg/dL | Standard Deviation 0.08 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 78 | 5.15 mg/dL | Standard Deviation 0.19 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 11 | 5.00 mg/dL | Standard Deviation 0.11 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 22 | 5.05 mg/dL | Standard Deviation 0.08 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 8 | 5.00 mg/dL | Standard Deviation 0.14 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 3 | 4.85 mg/dL | Standard Deviation 0.05 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 29 | 5.03 mg/dL | Standard Deviation 0.16 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 10 | 4.88 mg/dL | Standard Deviation 0.12 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 5 | 4.80 mg/dL | Standard Deviation 0.06 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 57 | 5.18 mg/dL | Standard Deviation 0.13 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 2 | 4.88 mg/dL | Standard Deviation 0.15 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 50 | 5.00 mg/dL | Standard Deviation 0.13 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 43 | 5.02 mg/dL | Standard Deviation 0.08 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 85 | 5.13 mg/dL | Standard Deviation 0.22 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 36 | 4.96 mg/dL | Standard Deviation 0.16 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 6 | 4.87 mg/dL | Standard Deviation 0.12 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 71 | 5.12 mg/dL | Standard Deviation 0.18 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 15 | 5.00 mg/dL | Standard Deviation 0.06 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 6 | 4.80 mg/dL | Standard Deviation 0.06 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 8 | 4.78 mg/dL | Standard Deviation 0.12 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 12 | 4.80 mg/dL | Standard Deviation 0.11 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 64 | 5.13 mg/dL | Standard Deviation 0.14 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Hour 4 | 4.95 mg/dL | Standard Deviation 0.08 |
| Romosozumab 10.0 mg/kg SC | Ionized Calcium Over Time | Day 1 Pre-dose | 4.85 mg/dL | Standard Deviation 0.1 |
| Placebo IV | Ionized Calcium Over Time | Day 3 | 5.28 mg/dL | Standard Deviation 0.13 |
| Placebo IV | Ionized Calcium Over Time | Day 78 | 5.15 mg/dL | Standard Deviation 0.07 |
| Placebo IV | Ionized Calcium Over Time | Day 11 | 5.23 mg/dL | Standard Deviation 0.13 |
| Placebo IV | Ionized Calcium Over Time | Day 4 | 5.23 mg/dL | Standard Deviation 0.17 |
| Placebo IV | Ionized Calcium Over Time | Day 15 | 5.20 mg/dL | Standard Deviation 0.22 |
| Placebo IV | Ionized Calcium Over Time | Day 1 Hour 4 | 5.40 mg/dL | Standard Deviation 0.14 |
| Placebo IV | Ionized Calcium Over Time | Day 85 | 5.20 mg/dL | Standard Deviation 0.14 |
| Placebo IV | Ionized Calcium Over Time | Day 71 | 5.30 mg/dL | Standard Deviation 0.28 |
| Placebo IV | Ionized Calcium Over Time | Day 22 | 5.18 mg/dL | Standard Deviation 0.24 |
| Placebo IV | Ionized Calcium Over Time | Day 29 | 5.28 mg/dL | Standard Deviation 0.17 |
| Placebo IV | Ionized Calcium Over Time | Day 1 Hour 10 | 5.30 mg/dL | Standard Deviation 0.12 |
| Placebo IV | Ionized Calcium Over Time | Day 36 | 5.28 mg/dL | Standard Deviation 0.13 |
| Placebo IV | Ionized Calcium Over Time | Day 1 Hour 8 | 5.30 mg/dL | Standard Deviation 0.08 |
| Placebo IV | Ionized Calcium Over Time | Day 43 | 5.23 mg/dL | Standard Deviation 0.17 |
| Placebo IV | Ionized Calcium Over Time | Day 2 | 5.28 mg/dL | Standard Deviation 0.1 |
| Placebo IV | Ionized Calcium Over Time | Day 50 | 5.28 mg/dL | Standard Deviation 0.15 |
| Placebo IV | Ionized Calcium Over Time | Day 1 Pre-dose | 5.30 mg/dL | Standard Deviation 0.12 |
| Placebo IV | Ionized Calcium Over Time | Day 1 Hour 12 | 5.28 mg/dL | Standard Deviation 0.22 |
| Placebo IV | Ionized Calcium Over Time | Day 57 | 5.33 mg/dL | Standard Deviation 0.17 |
| Placebo IV | Ionized Calcium Over Time | Day 1 Hour 6 | 5.10 mg/dL | Standard Deviation 0.14 |
| Placebo IV | Ionized Calcium Over Time | Day 6 | 5.23 mg/dL | Standard Deviation 0.1 |
| Placebo IV | Ionized Calcium Over Time | Day 64 | 5.15 mg/dL | Standard Deviation 0.07 |
| Placebo IV | Ionized Calcium Over Time | Day 5 | 5.40 mg/dL | Standard Deviation 0.14 |
| Placebo IV | Ionized Calcium Over Time | Day 8 | 5.23 mg/dL | Standard Deviation 0.17 |
| Romosozumab 1.0 mg/kg IV | Ionized Calcium Over Time | Day 43 | 5.30 mg/dL | Standard Deviation 0.13 |
| Romosozumab 1.0 mg/kg IV | Ionized Calcium Over Time | Day 1 Pre-dose | 5.18 mg/dL | Standard Deviation 0.15 |
| Romosozumab 1.0 mg/kg IV | Ionized Calcium Over Time | Day 50 | 5.32 mg/dL | Standard Deviation 0.13 |
| Romosozumab 1.0 mg/kg IV | Ionized Calcium Over Time | Day 2 | 5.08 mg/dL | Standard Deviation 0.08 |
| Romosozumab 1.0 mg/kg IV | Ionized Calcium Over Time | Day 1 Hour 6 | 5.28 mg/dL | Standard Deviation 0.15 |
| Romosozumab 1.0 mg/kg IV | Ionized Calcium Over Time | Day 1 Hour 4 | 5.35 mg/dL | Standard Deviation 0.18 |
| Romosozumab 1.0 mg/kg IV | Ionized Calcium Over Time | Day 3 | 5.17 mg/dL | Standard Deviation 0.12 |
| Romosozumab 1.0 mg/kg IV | Ionized Calcium Over Time | Day 6 | 5.23 mg/dL | Standard Deviation 0.12 |
| Romosozumab 1.0 mg/kg IV | Ionized Calcium Over Time | Day 1 Hour 8 | 5.28 mg/dL | Standard Deviation 0.17 |
| Romosozumab 1.0 mg/kg IV | Ionized Calcium Over Time | Day 5 | 5.18 mg/dL | Standard Deviation 0.12 |
| Romosozumab 1.0 mg/kg IV | Ionized Calcium Over Time | Day 1 Hour 12 | 5.25 mg/dL | Standard Deviation 0.1 |
| Romosozumab 1.0 mg/kg IV | Ionized Calcium Over Time | Day 29 | 5.22 mg/dL | Standard Deviation 0.1 |
| Romosozumab 1.0 mg/kg IV | Ionized Calcium Over Time | Day 11 | 5.20 mg/dL | Standard Deviation 0.13 |
| Romosozumab 1.0 mg/kg IV | Ionized Calcium Over Time | Day 22 | 5.12 mg/dL | Standard Deviation 0.15 |
| Romosozumab 1.0 mg/kg IV | Ionized Calcium Over Time | Day 8 | 5.17 mg/dL | Standard Deviation 0.12 |
| Romosozumab 1.0 mg/kg IV | Ionized Calcium Over Time | Day 15 | 5.25 mg/dL | Standard Deviation 0.12 |
| Romosozumab 1.0 mg/kg IV | Ionized Calcium Over Time | Day 57 | 5.23 mg/dL | Standard Deviation 0.08 |
| Romosozumab 1.0 mg/kg IV | Ionized Calcium Over Time | Day 4 | 5.20 mg/dL | Standard Deviation 0.09 |
| Romosozumab 1.0 mg/kg IV | Ionized Calcium Over Time | Day 1 Hour 10 | 5.32 mg/dL | Standard Deviation 0.18 |
| Romosozumab 1.0 mg/kg IV | Ionized Calcium Over Time | Day 36 | 5.18 mg/dL | Standard Deviation 0.1 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 29 | 5.13 mg/dL | Standard Deviation 0.2 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 36 | 5.18 mg/dL | Standard Deviation 0.15 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 4 | 5.17 mg/dL | Standard Deviation 0.14 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 1 Hour 12 | 5.33 mg/dL | Standard Deviation 0.08 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 15 | 5.07 mg/dL | Standard Deviation 0.12 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 1 Pre-dose | 5.27 mg/dL | Standard Deviation 0.15 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 2 | 5.18 mg/dL | Standard Deviation 0.1 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 6 | 5.05 mg/dL | Standard Deviation 0.1 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 43 | 5.18 mg/dL | Standard Deviation 0.12 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 1 Hour 6 | 5.30 mg/dL | Standard Deviation 0.09 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 1 Hour 10 | 5.38 mg/dL | Standard Deviation 0.15 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 1 Hour 4 | 5.40 mg/dL | Standard Deviation 0.09 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 8 | 5.07 mg/dL | Standard Deviation 0.19 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 50 | 5.15 mg/dL | Standard Deviation 0.14 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 5 | 5.15 mg/dL | Standard Deviation 0.14 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 11 | 5.10 mg/dL | Standard Deviation 0.2 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 57 | 5.25 mg/dL | Standard Deviation 0.15 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 1 Hour 8 | 5.30 mg/dL | Standard Deviation 0.09 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 78 | 5.27 mg/dL | Standard Deviation 0.15 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 64 | 5.17 mg/dL | Standard Deviation 0.14 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 85 | 5.23 mg/dL | Standard Deviation 0.14 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 3 | 5.25 mg/dL | Standard Deviation 0.14 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 71 | 5.20 mg/dL | Standard Deviation 0.13 |
| Romosozumab 5.0 mg/kg IV | Ionized Calcium Over Time | Day 22 | 5.05 mg/dL | Standard Deviation 0.21 |
Secondary
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.
Population: All treated participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Maximum Effect for Bone-specific Alkaline Phosphatase (BSAP) | 21.0 µg/L | Standard Deviation 5.7 |
| Romosozumab 0.1 mg/kg SC | Maximum Effect for Bone-specific Alkaline Phosphatase (BSAP) | 18.0 µg/L | Standard Deviation 6.7 |
| Romosozumab 0.3 mg/kg SC | Maximum Effect for Bone-specific Alkaline Phosphatase (BSAP) | 17.2 µg/L | Standard Deviation 3.2 |
| Romosozumab 1.0 mg/kg SC | Maximum Effect for Bone-specific Alkaline Phosphatase (BSAP) | 17.7 µg/L | Standard Deviation 4.7 |
| Romosozumab 3.0 mg/kg SC | Maximum Effect for Bone-specific Alkaline Phosphatase (BSAP) | 26.1 µg/L | Standard Deviation 7.8 |
| Romosozumab 5.0 mg/kg SC | Maximum Effect for Bone-specific Alkaline Phosphatase (BSAP) | 24.6 µg/L | Standard Deviation 8.6 |
| Romosozumab 10.0 mg/kg SC | Maximum Effect for Bone-specific Alkaline Phosphatase (BSAP) | 29.9 µg/L | Standard Deviation 8.2 |
| Placebo IV | Maximum Effect for Bone-specific Alkaline Phosphatase (BSAP) | 19.6 µg/L | Standard Deviation 3.7 |
| Romosozumab 1.0 mg/kg IV | Maximum Effect for Bone-specific Alkaline Phosphatase (BSAP) | 15.9 µg/L | Standard Deviation 4.5 |
| Romosozumab 5.0 mg/kg IV | Maximum Effect for Bone-specific Alkaline Phosphatase (BSAP) | 36.4 µg/L | Standard Deviation 15.9 |
Secondary
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.
Population: All treated participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Maximum Effect for Intact Parathyroid Hormone (iPTH) | 43.3 ng/L | Standard Deviation 12.6 |
| Romosozumab 0.1 mg/kg SC | Maximum Effect for Intact Parathyroid Hormone (iPTH) | 38.7 ng/L | Standard Deviation 11.9 |
| Romosozumab 0.3 mg/kg SC | Maximum Effect for Intact Parathyroid Hormone (iPTH) | 54.5 ng/L | Standard Deviation 13.1 |
| Romosozumab 1.0 mg/kg SC | Maximum Effect for Intact Parathyroid Hormone (iPTH) | 49.9 ng/L | Standard Deviation 20.5 |
| Romosozumab 3.0 mg/kg SC | Maximum Effect for Intact Parathyroid Hormone (iPTH) | 62.8 ng/L | Standard Deviation 10.9 |
| Romosozumab 5.0 mg/kg SC | Maximum Effect for Intact Parathyroid Hormone (iPTH) | 66.0 ng/L | Standard Deviation 20 |
| Romosozumab 10.0 mg/kg SC | Maximum Effect for Intact Parathyroid Hormone (iPTH) | 76.3 ng/L | Standard Deviation 15.7 |
| Placebo IV | Maximum Effect for Intact Parathyroid Hormone (iPTH) | 64.8 ng/L | Standard Deviation 27.8 |
| Romosozumab 1.0 mg/kg IV | Maximum Effect for Intact Parathyroid Hormone (iPTH) | 52.7 ng/L | Standard Deviation 20.1 |
| Romosozumab 5.0 mg/kg IV | Maximum Effect for Intact Parathyroid Hormone (iPTH) | 59.7 ng/L | Standard Deviation 14.9 |
Secondary
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.
Population: All treated participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Maximum Effect for Osteocalcin | 28.9 µg/L | Standard Deviation 8.1 |
| Romosozumab 0.1 mg/kg SC | Maximum Effect for Osteocalcin | 25.6 µg/L | Standard Deviation 8 |
| Romosozumab 0.3 mg/kg SC | Maximum Effect for Osteocalcin | 25.8 µg/L | Standard Deviation 4.8 |
| Romosozumab 1.0 mg/kg SC | Maximum Effect for Osteocalcin | 26.6 µg/L | Standard Deviation 5.5 |
| Romosozumab 3.0 mg/kg SC | Maximum Effect for Osteocalcin | 36.9 µg/L | Standard Deviation 10.9 |
| Romosozumab 5.0 mg/kg SC | Maximum Effect for Osteocalcin | 39.0 µg/L | Standard Deviation 12.7 |
| Romosozumab 10.0 mg/kg SC | Maximum Effect for Osteocalcin | 53.9 µg/L | Standard Deviation 10.5 |
| Placebo IV | Maximum Effect for Osteocalcin | 35.9 µg/L | Standard Deviation 13.9 |
| Romosozumab 1.0 mg/kg IV | Maximum Effect for Osteocalcin | 28.8 µg/L | Standard Deviation 7.7 |
| Romosozumab 5.0 mg/kg IV | Maximum Effect for Osteocalcin | 53.5 µg/L | Standard Deviation 12.8 |
Secondary
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.
Population: All treated participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Maximum Effect for Serum C-telopeptide (sCTX) | 0.3 ng/mL | Standard Deviation 0.2 |
| Romosozumab 0.1 mg/kg SC | Maximum Effect for Serum C-telopeptide (sCTX) | 0.4 ng/mL | Standard Deviation 0.2 |
| Romosozumab 0.3 mg/kg SC | Maximum Effect for Serum C-telopeptide (sCTX) | 0.3 ng/mL | Standard Deviation 0.1 |
| Romosozumab 1.0 mg/kg SC | Maximum Effect for Serum C-telopeptide (sCTX) | 0.3 ng/mL | Standard Deviation 0.1 |
| Romosozumab 3.0 mg/kg SC | Maximum Effect for Serum C-telopeptide (sCTX) | 0.4 ng/mL | Standard Deviation 0.1 |
| Romosozumab 5.0 mg/kg SC | Maximum Effect for Serum C-telopeptide (sCTX) | 0.2 ng/mL | Standard Deviation 0.1 |
| Romosozumab 10.0 mg/kg SC | Maximum Effect for Serum C-telopeptide (sCTX) | 0.2 ng/mL | Standard Deviation 0.1 |
| Placebo IV | Maximum Effect for Serum C-telopeptide (sCTX) | 0.3 ng/mL | Standard Deviation 0.2 |
| Romosozumab 1.0 mg/kg IV | Maximum Effect for Serum C-telopeptide (sCTX) | 0.2 ng/mL | Standard Deviation 0.1 |
| Romosozumab 5.0 mg/kg IV | Maximum Effect for Serum C-telopeptide (sCTX) | 0.2 ng/mL | Standard Deviation 0.1 |
Secondary
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.
Population: All treated participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Maximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP) | 69.8 ng/mL | Standard Deviation 32 |
| Romosozumab 0.1 mg/kg SC | Maximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP) | 57.7 ng/mL | Standard Deviation 22.8 |
| Romosozumab 0.3 mg/kg SC | Maximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP) | 60.9 ng/mL | Standard Deviation 14.4 |
| Romosozumab 1.0 mg/kg SC | Maximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP) | 60.7 ng/mL | Standard Deviation 10.8 |
| Romosozumab 3.0 mg/kg SC | Maximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP) | 100.8 ng/mL | Standard Deviation 49.6 |
| Romosozumab 5.0 mg/kg SC | Maximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP) | 125.1 ng/mL | Standard Deviation 44.2 |
| Romosozumab 10.0 mg/kg SC | Maximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP) | 141.4 ng/mL | Standard Deviation 24.8 |
| Placebo IV | Maximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP) | 77.0 ng/mL | Standard Deviation 35.3 |
| Romosozumab 1.0 mg/kg IV | Maximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP) | 76.3 ng/mL | Standard Deviation 19.8 |
| Romosozumab 5.0 mg/kg IV | Maximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP) | 173.4 ng/mL | Standard Deviation 43.3 |
Secondary
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.
Population: All treated participants who received subcutaneous romosozumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC | Maximum Observed Concentration (Cmax) of Romosozumab | 375 ng/mL | Standard Deviation 182 |
| Romosozumab 0.1 mg/kg SC | Maximum Observed Concentration (Cmax) of Romosozumab | 1280 ng/mL | Standard Deviation 653 |
| Romosozumab 0.3 mg/kg SC | Maximum Observed Concentration (Cmax) of Romosozumab | 4890 ng/mL | Standard Deviation 1780 |
| Romosozumab 1.0 mg/kg SC | Maximum Observed Concentration (Cmax) of Romosozumab | 21300 ng/mL | Standard Deviation 5170 |
| Romosozumab 3.0 mg/kg SC | Maximum Observed Concentration (Cmax) of Romosozumab | 33500 ng/mL | Standard Deviation 8290 |
| Romosozumab 5.0 mg/kg SC | Maximum Observed Concentration (Cmax) of Romosozumab | 75200 ng/mL | Standard Deviation 15900 |
Secondary
Percent Change From Baseline in Sclerostin
Time frame: Baseline and days 15, 29, 43, 57, 71, and 85
Population: All treated participants; only participants who received ≥ 1 mg/kg romosozumab/placebo were assessed after day 29 and only participants who received 5 or 10 mg/kg romosozumab/placebo were assessed on days 71 and 85.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo SC | Percent Change From Baseline in Sclerostin | Day 85 | 11.6 percent change | Standard Deviation 16.6 |
| Placebo SC | Percent Change From Baseline in Sclerostin | Day 71 | 86.9 percent change | Standard Deviation 88.3 |
| Placebo SC | Percent Change From Baseline in Sclerostin | Day 57 | -3.7 percent change | Standard Deviation 8.6 |
| Placebo SC | Percent Change From Baseline in Sclerostin | Day 43 | -9.8 percent change | Standard Deviation 14.1 |
| Placebo SC | Percent Change From Baseline in Sclerostin | Day 15 | 53.2 percent change | Standard Deviation 54.3 |
| Placebo SC | Percent Change From Baseline in Sclerostin | Day 29 | -8.4 percent change | Standard Deviation 7 |
| Romosozumab 0.1 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 15 | 465.5 percent change | Standard Deviation 49.9 |
| Romosozumab 0.1 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 29 | 129.0 percent change | Standard Deviation 33.3 |
| Romosozumab 0.3 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 29 | 183.0 percent change | Standard Deviation 19.6 |
| Romosozumab 0.3 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 15 | 835.1 percent change | Standard Deviation 130.4 |
| Romosozumab 1.0 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 57 | 83.4 percent change | Standard Deviation 14.5 |
| Romosozumab 1.0 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 43 | 223.2 percent change | Standard Deviation 18.1 |
| Romosozumab 1.0 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 15 | 2123.8 percent change | Standard Deviation 377.6 |
| Romosozumab 1.0 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 29 | 717.4 percent change | Standard Deviation 92.4 |
| Romosozumab 3.0 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 29 | 5140.2 percent change | Standard Deviation 373.7 |
| Romosozumab 3.0 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 43 | 1988.3 percent change | Standard Deviation 339.9 |
| Romosozumab 3.0 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 57 | 810.2 percent change | Standard Deviation 169.9 |
| Romosozumab 3.0 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 15 | 7965.9 percent change | Standard Deviation 792.9 |
| Romosozumab 5.0 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 43 | 4968.7 percent change | Standard Deviation 714.7 |
| Romosozumab 5.0 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 15 | 12375.7 percent change | Standard Deviation 1375.4 |
| Romosozumab 5.0 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 29 | 9763.2 percent change | Standard Deviation 1252.8 |
| Romosozumab 5.0 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 57 | 2004.9 percent change | Standard Deviation 421.5 |
| Romosozumab 5.0 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 71 | 610.4 percent change | Standard Deviation 151.6 |
| Romosozumab 5.0 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 85 | 232.1 percent change | Standard Deviation 49 |
| Romosozumab 10.0 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 57 | 6469.6 percent change | Standard Deviation 1000.3 |
| Romosozumab 10.0 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 85 | 758.0 percent change | Standard Deviation 270.1 |
| Romosozumab 10.0 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 43 | 13902.7 percent change | Standard Deviation 2381.9 |
| Romosozumab 10.0 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 15 | 17774.8 percent change | Standard Deviation 2444 |
| Romosozumab 10.0 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 29 | 18870.9 percent change | Standard Deviation 2707.3 |
| Romosozumab 10.0 mg/kg SC | Percent Change From Baseline in Sclerostin | Day 71 | 2080.8 percent change | Standard Deviation 689 |
| Placebo IV | Percent Change From Baseline in Sclerostin | Day 29 | -4.3 percent change | Standard Deviation 8.7 |
| Placebo IV | Percent Change From Baseline in Sclerostin | Day 43 | 4.9 percent change | Standard Deviation 8.7 |
| Placebo IV | Percent Change From Baseline in Sclerostin | Day 57 | 15.6 percent change | Standard Deviation 0.6 |
| Placebo IV | Percent Change From Baseline in Sclerostin | Day 15 | 6.7 percent change | Standard Deviation 11.4 |
| Placebo IV | Percent Change From Baseline in Sclerostin | Day 85 | 0.8 percent change | Standard Deviation 13.4 |
| Placebo IV | Percent Change From Baseline in Sclerostin | Day 71 | -5.5 percent change | Standard Deviation 5.4 |
| Romosozumab 1.0 mg/kg IV | Percent Change From Baseline in Sclerostin | Day 15 | 3776.0 percent change | Standard Deviation 461.5 |
| Romosozumab 1.0 mg/kg IV | Percent Change From Baseline in Sclerostin | Day 29 | 816.7 percent change | Standard Deviation 222.3 |
| Romosozumab 1.0 mg/kg IV | Percent Change From Baseline in Sclerostin | Day 57 | 49.9 percent change | Standard Deviation 17.4 |
| Romosozumab 1.0 mg/kg IV | Percent Change From Baseline in Sclerostin | Day 43 | 196.1 percent change | Standard Deviation 48.7 |
| Romosozumab 5.0 mg/kg IV | Percent Change From Baseline in Sclerostin | Day 85 | 109.8 percent change | Standard Deviation 30.6 |
| Romosozumab 5.0 mg/kg IV | Percent Change From Baseline in Sclerostin | Day 29 | 11715.5 percent change | Standard Deviation 2177 |
| Romosozumab 5.0 mg/kg IV | Percent Change From Baseline in Sclerostin | Day 57 | 1430.0 percent change | Standard Deviation 538 |
| Romosozumab 5.0 mg/kg IV | Percent Change From Baseline in Sclerostin | Day 15 | 14230.0 percent change | Standard Deviation 2428.1 |
| Romosozumab 5.0 mg/kg IV | Percent Change From Baseline in Sclerostin | Day 71 | 426.9 percent change | Standard Deviation 119.6 |
| Romosozumab 5.0 mg/kg IV | Percent Change From Baseline in Sclerostin | Day 43 | 4576.0 percent change | Standard Deviation 1086.7 |
Secondary
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
Population: All treated participants; only participants who received ≥ 1 mg/kg romosozumab/placebo were assessed after day 29 and only participants who received 5 or 10 mg/kg romosozumab/placebo were assessed after day 57.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo SC | Serum Calcium Over Time | Day 1 Hour 10 | 9.53 mg/dL | Standard Deviation 0.26 |
| Placebo SC | Serum Calcium Over Time | Day 50 | 9.35 mg/dL | Standard Deviation 0.26 |
| Placebo SC | Serum Calcium Over Time | Day 43 | 9.33 mg/dL | Standard Deviation 0.39 |
| Placebo SC | Serum Calcium Over Time | Day 1 Hour 4 | 9.46 mg/dL | Standard Deviation 0.3 |
| Placebo SC | Serum Calcium Over Time | Day 1 Pre-dose | 9.49 mg/dL | Standard Deviation 0.34 |
| Placebo SC | Serum Calcium Over Time | Day 36 | 9.40 mg/dL | Standard Deviation 0.45 |
| Placebo SC | Serum Calcium Over Time | Day 29 | 9.49 mg/dL | Standard Deviation 0.32 |
| Placebo SC | Serum Calcium Over Time | Day 22 | 9.35 mg/dL | Standard Deviation 0.33 |
| Placebo SC | Serum Calcium Over Time | Day 15 | 9.39 mg/dL | Standard Deviation 0.26 |
| Placebo SC | Serum Calcium Over Time | Day 11 | 9.32 mg/dL | Standard Deviation 0.29 |
| Placebo SC | Serum Calcium Over Time | Day 8 | 9.41 mg/dL | Standard Deviation 0.31 |
| Placebo SC | Serum Calcium Over Time | Day 6 | 9.56 mg/dL | Standard Deviation 0.26 |
| Placebo SC | Serum Calcium Over Time | Day 1 Hour 8 | 9.38 mg/dL | Standard Deviation 0.22 |
| Placebo SC | Serum Calcium Over Time | Day 5 | 9.42 mg/dL | Standard Deviation 0.36 |
| Placebo SC | Serum Calcium Over Time | Day 4 | 9.49 mg/dL | Standard Deviation 0.25 |
| Placebo SC | Serum Calcium Over Time | Day 3 | 9.30 mg/dL | Standard Deviation 0.61 |
| Placebo SC | Serum Calcium Over Time | Day 2 | 9.46 mg/dL | Standard Deviation 0.34 |
| Placebo SC | Serum Calcium Over Time | Day 85 | 9.12 mg/dL | Standard Deviation 0.08 |
| Placebo SC | Serum Calcium Over Time | Day 1 Hour 6 | 9.49 mg/dL | Standard Deviation 0.26 |
| Placebo SC | Serum Calcium Over Time | Day 1 Hour 12 | 9.53 mg/dL | Standard Deviation 0.28 |
| Placebo SC | Serum Calcium Over Time | Day 78 | 9.30 mg/dL | Standard Deviation 0.24 |
| Placebo SC | Serum Calcium Over Time | Day 71 | 9.36 mg/dL | Standard Deviation 0.18 |
| Placebo SC | Serum Calcium Over Time | Day 64 | 9.22 mg/dL | Standard Deviation 0.15 |
| Placebo SC | Serum Calcium Over Time | Day 57 | 9.46 mg/dL | Standard Deviation 0.3 |
| Romosozumab 0.1 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 10 | 9.62 mg/dL | Standard Deviation 0.31 |
| Romosozumab 0.1 mg/kg SC | Serum Calcium Over Time | Day 5 | 9.38 mg/dL | Standard Deviation 0.21 |
| Romosozumab 0.1 mg/kg SC | Serum Calcium Over Time | Day 22 | 9.53 mg/dL | Standard Deviation 0.45 |
| Romosozumab 0.1 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 12 | 9.55 mg/dL | Standard Deviation 0.27 |
| Romosozumab 0.1 mg/kg SC | Serum Calcium Over Time | Day 2 | 9.55 mg/dL | Standard Deviation 0.21 |
| Romosozumab 0.1 mg/kg SC | Serum Calcium Over Time | Day 15 | 9.60 mg/dL | Standard Deviation 0.17 |
| Romosozumab 0.1 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 8 | 9.47 mg/dL | Standard Deviation 0.29 |
| Romosozumab 0.1 mg/kg SC | Serum Calcium Over Time | Day 1 Pre-dose | 9.45 mg/dL | Standard Deviation 0.38 |
| Romosozumab 0.1 mg/kg SC | Serum Calcium Over Time | Day 11 | 9.38 mg/dL | Standard Deviation 0.33 |
| Romosozumab 0.1 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 6 | 9.38 mg/dL | Standard Deviation 0.22 |
| Romosozumab 0.1 mg/kg SC | Serum Calcium Over Time | Day 8 | 9.45 mg/dL | Standard Deviation 0.2 |
| Romosozumab 0.1 mg/kg SC | Serum Calcium Over Time | Day 3 | 9.37 mg/dL | Standard Deviation 0.29 |
| Romosozumab 0.1 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 4 | 9.62 mg/dL | Standard Deviation 0.19 |
| Romosozumab 0.1 mg/kg SC | Serum Calcium Over Time | Day 6 | 9.45 mg/dL | Standard Deviation 0.29 |
| Romosozumab 0.1 mg/kg SC | Serum Calcium Over Time | Day 4 | 9.38 mg/dL | Standard Deviation 0.27 |
| Romosozumab 0.1 mg/kg SC | Serum Calcium Over Time | Day 29 | 9.58 mg/dL | Standard Deviation 0.22 |
| Romosozumab 0.3 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 12 | 9.57 mg/dL | Standard Deviation 0.31 |
| Romosozumab 0.3 mg/kg SC | Serum Calcium Over Time | Day 1 Pre-dose | 9.50 mg/dL | Standard Deviation 0.33 |
| Romosozumab 0.3 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 4 | 9.45 mg/dL | Standard Deviation 0.26 |
| Romosozumab 0.3 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 6 | 9.50 mg/dL | Standard Deviation 0.14 |
| Romosozumab 0.3 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 8 | 9.33 mg/dL | Standard Deviation 0.23 |
| Romosozumab 0.3 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 10 | 9.50 mg/dL | Standard Deviation 0.27 |
| Romosozumab 0.3 mg/kg SC | Serum Calcium Over Time | Day 2 | 9.23 mg/dL | Standard Deviation 0.28 |
| Romosozumab 0.3 mg/kg SC | Serum Calcium Over Time | Day 3 | 9.25 mg/dL | Standard Deviation 0.39 |
| Romosozumab 0.3 mg/kg SC | Serum Calcium Over Time | Day 4 | 9.37 mg/dL | Standard Deviation 0.27 |
| Romosozumab 0.3 mg/kg SC | Serum Calcium Over Time | Day 5 | 9.37 mg/dL | Standard Deviation 0.25 |
| Romosozumab 0.3 mg/kg SC | Serum Calcium Over Time | Day 6 | 9.45 mg/dL | Standard Deviation 0.26 |
| Romosozumab 0.3 mg/kg SC | Serum Calcium Over Time | Day 8 | 9.28 mg/dL | Standard Deviation 0.23 |
| Romosozumab 0.3 mg/kg SC | Serum Calcium Over Time | Day 11 | 9.07 mg/dL | Standard Deviation 0.24 |
| Romosozumab 0.3 mg/kg SC | Serum Calcium Over Time | Day 15 | 9.40 mg/dL | Standard Deviation 0.32 |
| Romosozumab 0.3 mg/kg SC | Serum Calcium Over Time | Day 22 | 9.18 mg/dL | Standard Deviation 0.35 |
| Romosozumab 0.3 mg/kg SC | Serum Calcium Over Time | Day 29 | 9.40 mg/dL | Standard Deviation 0.26 |
| Romosozumab 1.0 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 4 | 9.38 mg/dL | Standard Deviation 0.16 |
| Romosozumab 1.0 mg/kg SC | Serum Calcium Over Time | Day 57 | 9.47 mg/dL | Standard Deviation 0.36 |
| Romosozumab 1.0 mg/kg SC | Serum Calcium Over Time | Day 29 | 9.44 mg/dL | Standard Deviation 0.37 |
| Romosozumab 1.0 mg/kg SC | Serum Calcium Over Time | Day 1 Pre-dose | 9.48 mg/dL | Standard Deviation 0.27 |
| Romosozumab 1.0 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 10 | 9.40 mg/dL | Standard Deviation 0.3 |
| Romosozumab 1.0 mg/kg SC | Serum Calcium Over Time | Day 50 | 9.30 mg/dL | Standard Deviation 0.41 |
| Romosozumab 1.0 mg/kg SC | Serum Calcium Over Time | Day 2 | 9.39 mg/dL | Standard Deviation 0.21 |
| Romosozumab 1.0 mg/kg SC | Serum Calcium Over Time | Day 4 | 9.18 mg/dL | Standard Deviation 0.64 |
| Romosozumab 1.0 mg/kg SC | Serum Calcium Over Time | Day 43 | 9.32 mg/dL | Standard Deviation 0.21 |
| Romosozumab 1.0 mg/kg SC | Serum Calcium Over Time | Day 8 | 9.36 mg/dL | Standard Deviation 0.44 |
| Romosozumab 1.0 mg/kg SC | Serum Calcium Over Time | Day 22 | 9.33 mg/dL | Standard Deviation 0.32 |
| Romosozumab 1.0 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 12 | 9.49 mg/dL | Standard Deviation 0.31 |
| Romosozumab 1.0 mg/kg SC | Serum Calcium Over Time | Day 15 | 9.26 mg/dL | Standard Deviation 0.21 |
| Romosozumab 1.0 mg/kg SC | Serum Calcium Over Time | Day 3 | 9.20 mg/dL | Standard Deviation 0.34 |
| Romosozumab 1.0 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 8 | 9.29 mg/dL | Standard Deviation 0.18 |
| Romosozumab 1.0 mg/kg SC | Serum Calcium Over Time | Day 11 | 9.39 mg/dL | Standard Deviation 0.25 |
| Romosozumab 1.0 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 6 | 9.47 mg/dL | Standard Deviation 0.17 |
| Romosozumab 1.0 mg/kg SC | Serum Calcium Over Time | Day 5 | 9.38 mg/dL | Standard Deviation 0.24 |
| Romosozumab 1.0 mg/kg SC | Serum Calcium Over Time | Day 6 | 9.51 mg/dL | Standard Deviation 0.2 |
| Romosozumab 1.0 mg/kg SC | Serum Calcium Over Time | Day 36 | 9.33 mg/dL | Standard Deviation 0.26 |
| Romosozumab 3.0 mg/kg SC | Serum Calcium Over Time | Day 57 | 9.35 mg/dL | Standard Deviation 0.29 |
| Romosozumab 3.0 mg/kg SC | Serum Calcium Over Time | Day 8 | 9.23 mg/dL | Standard Deviation 0.1 |
| Romosozumab 3.0 mg/kg SC | Serum Calcium Over Time | Day 6 | 9.35 mg/dL | Standard Deviation 0.1 |
| Romosozumab 3.0 mg/kg SC | Serum Calcium Over Time | Day 1 Pre-dose | 9.42 mg/dL | Standard Deviation 0.25 |
| Romosozumab 3.0 mg/kg SC | Serum Calcium Over Time | Day 2 | 9.37 mg/dL | Standard Deviation 0.33 |
| Romosozumab 3.0 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 12 | 9.37 mg/dL | Standard Deviation 0.34 |
| Romosozumab 3.0 mg/kg SC | Serum Calcium Over Time | Day 50 | 9.03 mg/dL | Standard Deviation 0.21 |
| Romosozumab 3.0 mg/kg SC | Serum Calcium Over Time | Day 43 | 9.37 mg/dL | Standard Deviation 0.31 |
| Romosozumab 3.0 mg/kg SC | Serum Calcium Over Time | Day 36 | 9.23 mg/dL | Standard Deviation 0.3 |
| Romosozumab 3.0 mg/kg SC | Serum Calcium Over Time | Day 3 | 9.35 mg/dL | Standard Deviation 0.14 |
| Romosozumab 3.0 mg/kg SC | Serum Calcium Over Time | Day 29 | 9.20 mg/dL | Standard Deviation 0.27 |
| Romosozumab 3.0 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 4 | 9.38 mg/dL | Standard Deviation 0.15 |
| Romosozumab 3.0 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 8 | 9.28 mg/dL | Standard Deviation 0.12 |
| Romosozumab 3.0 mg/kg SC | Serum Calcium Over Time | Day 22 | 9.22 mg/dL | Standard Deviation 0.17 |
| Romosozumab 3.0 mg/kg SC | Serum Calcium Over Time | Day 4 | 9.27 mg/dL | Standard Deviation 0.12 |
| Romosozumab 3.0 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 10 | 9.38 mg/dL | Standard Deviation 0.19 |
| Romosozumab 3.0 mg/kg SC | Serum Calcium Over Time | Day 15 | 9.22 mg/dL | Standard Deviation 0.19 |
| Romosozumab 3.0 mg/kg SC | Serum Calcium Over Time | Day 11 | 9.30 mg/dL | Standard Deviation 0.39 |
| Romosozumab 3.0 mg/kg SC | Serum Calcium Over Time | Day 5 | 9.32 mg/dL | Standard Deviation 0.25 |
| Romosozumab 3.0 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 6 | 9.60 mg/dL | Standard Deviation 0.24 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 3 | 9.38 mg/dL | Standard Deviation 0.41 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 2 | 9.46 mg/dL | Standard Deviation 0.29 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 78 | 9.31 mg/dL | Standard Deviation 0.32 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 8 | 9.42 mg/dL | Standard Deviation 0.28 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 4 | 9.40 mg/dL | Standard Deviation 0.3 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 5 | 9.24 mg/dL | Standard Deviation 0.26 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 6 | 9.36 mg/dL | Standard Deviation 0.26 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 6 | 9.48 mg/dL | Standard Deviation 0.35 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 8 | 9.33 mg/dL | Standard Deviation 0.4 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 85 | 9.47 mg/dL | Standard Deviation 0.35 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 11 | 9.19 mg/dL | Standard Deviation 0.36 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 15 | 9.06 mg/dL | Standard Deviation 0.35 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 22 | 9.14 mg/dL | Standard Deviation 0.47 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 4 | 9.59 mg/dL | Standard Deviation 0.27 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 29 | 9.32 mg/dL | Standard Deviation 0.28 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 36 | 9.00 mg/dL | Standard Deviation 0.26 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 43 | 9.23 mg/dL | Standard Deviation 0.36 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 50 | 9.40 mg/dL | Standard Deviation 0.34 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 57 | 9.18 mg/dL | Standard Deviation 0.49 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 64 | 9.28 mg/dL | Standard Deviation 0.42 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 1 Pre-dose | 9.53 mg/dL | Standard Deviation 0.26 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 71 | 9.47 mg/dL | Standard Deviation 0.47 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 10 | 9.36 mg/dL | Standard Deviation 0.31 |
| Romosozumab 5.0 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 12 | 9.52 mg/dL | Standard Deviation 0.26 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 10 | 9.28 mg/dL | Standard Deviation 0.27 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 6 | 9.25 mg/dL | Standard Deviation 0.36 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 43 | 8.90 mg/dL | Standard Deviation 0.26 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 8 | 8.93 mg/dL | Standard Deviation 0.28 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 2 | 9.23 mg/dL | Standard Deviation 0.29 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 85 | 8.82 mg/dL | Standard Deviation 0.31 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 50 | 8.98 mg/dL | Standard Deviation 0.19 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 71 | 9.05 mg/dL | Standard Deviation 0.36 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 15 | 8.97 mg/dL | Standard Deviation 0.18 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 5 | 9.15 mg/dL | Standard Deviation 0.18 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 4 | 9.35 mg/dL | Standard Deviation 0.4 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 4 | 9.13 mg/dL | Standard Deviation 0.22 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 78 | 9.07 mg/dL | Standard Deviation 0.4 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 22 | 8.90 mg/dL | Standard Deviation 0.23 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 11 | 8.70 mg/dL | Standard Deviation 0.75 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 6 | 9.18 mg/dL | Standard Deviation 0.15 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 64 | 8.90 mg/dL | Standard Deviation 0.36 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 57 | 9.28 mg/dL | Standard Deviation 0.17 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 29 | 8.95 mg/dL | Standard Deviation 0.19 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 1 Pre-dose | 9.38 mg/dL | Standard Deviation 0.24 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 3 | 9.18 mg/dL | Standard Deviation 0.17 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 12 | 9.27 mg/dL | Standard Deviation 0.34 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 1 Hour 8 | 9.27 mg/dL | Standard Deviation 0.33 |
| Romosozumab 10.0 mg/kg SC | Serum Calcium Over Time | Day 36 | 9.07 mg/dL | Standard Deviation 0.26 |
| Placebo IV | Serum Calcium Over Time | Day 64 | 9.25 mg/dL | Standard Deviation 0.07 |
| Placebo IV | Serum Calcium Over Time | Day 1 Hour 8 | 9.38 mg/dL | Standard Deviation 0.21 |
| Placebo IV | Serum Calcium Over Time | Day 1 Hour 12 | 9.40 mg/dL | Standard Deviation 0.24 |
| Placebo IV | Serum Calcium Over Time | Day 71 | 9.20 mg/dL | Standard Deviation 0.14 |
| Placebo IV | Serum Calcium Over Time | Day 29 | 9.38 mg/dL | Standard Deviation 0.13 |
| Placebo IV | Serum Calcium Over Time | Day 43 | 9.28 mg/dL | Standard Deviation 0.33 |
| Placebo IV | Serum Calcium Over Time | Day 22 | 9.48 mg/dL | Standard Deviation 0.13 |
| Placebo IV | Serum Calcium Over Time | Day 8 | 9.30 mg/dL | Standard Deviation 0.22 |
| Placebo IV | Serum Calcium Over Time | Day 6 | 9.35 mg/dL | Standard Deviation 0.24 |
| Placebo IV | Serum Calcium Over Time | Day 5 | 9.55 mg/dL | Standard Deviation 0.17 |
| Placebo IV | Serum Calcium Over Time | Day 2 | 8.55 mg/dL | Standard Deviation 1.77 |
| Placebo IV | Serum Calcium Over Time | Day 1 Pre-dose | 9.60 mg/dL | Standard Deviation 0.22 |
| Placebo IV | Serum Calcium Over Time | Day 1 Hour 10 | 9.50 mg/dL | Standard Deviation 0.22 |
| Placebo IV | Serum Calcium Over Time | Day 50 | 9.33 mg/dL | Standard Deviation 0.33 |
| Placebo IV | Serum Calcium Over Time | Day 4 | 9.23 mg/dL | Standard Deviation 0.5 |
| Placebo IV | Serum Calcium Over Time | Day 57 | 9.33 mg/dL | Standard Deviation 0.29 |
| Placebo IV | Serum Calcium Over Time | Day 1 Hour 6 | 9.18 mg/dL | Standard Deviation 0.13 |
| Placebo IV | Serum Calcium Over Time | Day 15 | 9.33 mg/dL | Standard Deviation 0.22 |
| Placebo IV | Serum Calcium Over Time | Day 78 | 9.20 mg/dL | Standard Deviation 0 |
| Placebo IV | Serum Calcium Over Time | Day 11 | 9.30 mg/dL | Standard Deviation 0.22 |
| Placebo IV | Serum Calcium Over Time | Day 1 Hour 4 | 9.45 mg/dL | Standard Deviation 0.21 |
| Placebo IV | Serum Calcium Over Time | Day 3 | 9.40 mg/dL | Standard Deviation 0.24 |
| Placebo IV | Serum Calcium Over Time | Day 85 | 9.10 mg/dL | Standard Deviation 0.28 |
| Placebo IV | Serum Calcium Over Time | Day 36 | 9.25 mg/dL | Standard Deviation 0.3 |
| Romosozumab 1.0 mg/kg IV | Serum Calcium Over Time | Day 6 | 9.32 mg/dL | Standard Deviation 0.19 |
| Romosozumab 1.0 mg/kg IV | Serum Calcium Over Time | Day 1 Hour 12 | 9.47 mg/dL | Standard Deviation 0.19 |
| Romosozumab 1.0 mg/kg IV | Serum Calcium Over Time | Day 11 | 9.13 mg/dL | Standard Deviation 0.29 |
| Romosozumab 1.0 mg/kg IV | Serum Calcium Over Time | Day 1 Hour 4 | 9.43 mg/dL | Standard Deviation 0.22 |
| Romosozumab 1.0 mg/kg IV | Serum Calcium Over Time | Day 4 | 8.88 mg/dL | Standard Deviation 0.84 |
| Romosozumab 1.0 mg/kg IV | Serum Calcium Over Time | Day 15 | 9.28 mg/dL | Standard Deviation 0.33 |
| Romosozumab 1.0 mg/kg IV | Serum Calcium Over Time | Day 22 | 9.18 mg/dL | Standard Deviation 0.22 |
| Romosozumab 1.0 mg/kg IV | Serum Calcium Over Time | Day 3 | 9.13 mg/dL | Standard Deviation 0.51 |
| Romosozumab 1.0 mg/kg IV | Serum Calcium Over Time | Day 29 | 9.17 mg/dL | Standard Deviation 0.21 |
| Romosozumab 1.0 mg/kg IV | Serum Calcium Over Time | Day 36 | 9.18 mg/dL | Standard Deviation 0.35 |
| Romosozumab 1.0 mg/kg IV | Serum Calcium Over Time | Day 1 Hour 10 | 9.45 mg/dL | Standard Deviation 0.16 |
| Romosozumab 1.0 mg/kg IV | Serum Calcium Over Time | Day 43 | 9.25 mg/dL | Standard Deviation 0.25 |
| Romosozumab 1.0 mg/kg IV | Serum Calcium Over Time | Day 1 Pre-dose | 9.23 mg/dL | Standard Deviation 0.15 |
| Romosozumab 1.0 mg/kg IV | Serum Calcium Over Time | Day 2 | 9.05 mg/dL | Standard Deviation 0.41 |
| Romosozumab 1.0 mg/kg IV | Serum Calcium Over Time | Day 50 | 9.43 mg/dL | Standard Deviation 0.5 |
| Romosozumab 1.0 mg/kg IV | Serum Calcium Over Time | Day 1 Hour 8 | 9.35 mg/dL | Standard Deviation 0.1 |
| Romosozumab 1.0 mg/kg IV | Serum Calcium Over Time | Day 57 | 9.25 mg/dL | Standard Deviation 0.27 |
| Romosozumab 1.0 mg/kg IV | Serum Calcium Over Time | Day 1 Hour 6 | 9.38 mg/dL | Standard Deviation 0.31 |
| Romosozumab 1.0 mg/kg IV | Serum Calcium Over Time | Day 5 | 9.20 mg/dL | Standard Deviation 0.15 |
| Romosozumab 1.0 mg/kg IV | Serum Calcium Over Time | Day 8 | 9.18 mg/dL | Standard Deviation 0.29 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 1 Pre-dose | 9.37 mg/dL | Standard Deviation 0.15 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 36 | 9.00 mg/dL | Standard Deviation 0.3 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 1 Hour 6 | 9.40 mg/dL | Standard Deviation 0.15 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 57 | 9.02 mg/dL | Standard Deviation 0.21 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 29 | 9.15 mg/dL | Standard Deviation 0.23 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 1 Hour 8 | 9.22 mg/dL | Standard Deviation 0.12 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 78 | 9.12 mg/dL | Standard Deviation 0.34 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 85 | 9.05 mg/dL | Standard Deviation 0.26 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 1 Hour 12 | 9.45 mg/dL | Standard Deviation 0.19 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 3 | 9.27 mg/dL | Standard Deviation 0.18 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 71 | 9.20 mg/dL | Standard Deviation 0.14 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 22 | 9.08 mg/dL | Standard Deviation 0.15 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 15 | 9.00 mg/dL | Standard Deviation 0.36 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 6 | 9.23 mg/dL | Standard Deviation 0.12 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 1 Hour 4 | 9.40 mg/dL | Standard Deviation 0.17 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 11 | 9.18 mg/dL | Standard Deviation 0.26 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 5 | 9.12 mg/dL | Standard Deviation 0.19 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 8 | 9.20 mg/dL | Standard Deviation 0.37 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 4 | 9.18 mg/dL | Standard Deviation 0.13 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 50 | 9.07 mg/dL | Standard Deviation 0.23 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 1 Hour 10 | 9.42 mg/dL | Standard Deviation 0.15 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 43 | 9.15 mg/dL | Standard Deviation 0.33 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 64 | 9.18 mg/dL | Standard Deviation 0.35 |
| Romosozumab 5.0 mg/kg IV | Serum Calcium Over Time | Day 2 | 9.28 mg/dL | Standard Deviation 0.15 |
Secondary
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.
Population: All treated participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo SC | Time to Maximum Effect of BSAP | 36.0 days |
| Romosozumab 0.1 mg/kg SC | Time to Maximum Effect of BSAP | 16.5 days |
| Romosozumab 0.3 mg/kg SC | Time to Maximum Effect of BSAP | 13.0 days |
| Romosozumab 1.0 mg/kg SC | Time to Maximum Effect of BSAP | 15.0 days |
| Romosozumab 3.0 mg/kg SC | Time to Maximum Effect of BSAP | 22.0 days |
| Romosozumab 5.0 mg/kg SC | Time to Maximum Effect of BSAP | 22.0 days |
| Romosozumab 10.0 mg/kg SC | Time to Maximum Effect of BSAP | 22.0 days |
| Placebo IV | Time to Maximum Effect of BSAP | 46.5 days |
| Romosozumab 1.0 mg/kg IV | Time to Maximum Effect of BSAP | 13.5 days |
| Romosozumab 5.0 mg/kg IV | Time to Maximum Effect of BSAP | 29.0 days |
Secondary
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.
Population: All treated participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo SC | Time to Maximum Effect of iPTH | 11.0 days |
| Romosozumab 0.1 mg/kg SC | Time to Maximum Effect of iPTH | 11.0 days |
| Romosozumab 0.3 mg/kg SC | Time to Maximum Effect of iPTH | 25.5 days |
| Romosozumab 1.0 mg/kg SC | Time to Maximum Effect of iPTH | 22.0 days |
| Romosozumab 3.0 mg/kg SC | Time to Maximum Effect of iPTH | 22.0 days |
| Romosozumab 5.0 mg/kg SC | Time to Maximum Effect of iPTH | 22.0 days |
| Romosozumab 10.0 mg/kg SC | Time to Maximum Effect of iPTH | 15.0 days |
| Placebo IV | Time to Maximum Effect of iPTH | 25.5 days |
| Romosozumab 1.0 mg/kg IV | Time to Maximum Effect of iPTH | 11.0 days |
| Romosozumab 5.0 mg/kg IV | Time to Maximum Effect of iPTH | 18.5 days |
Secondary
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.
Population: All treated participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo SC | Time to Maximum Effect of Osteocalcin | 29.0 days |
| Romosozumab 0.1 mg/kg SC | Time to Maximum Effect of Osteocalcin | 15.0 days |
| Romosozumab 0.3 mg/kg SC | Time to Maximum Effect of Osteocalcin | 18.5 days |
| Romosozumab 1.0 mg/kg SC | Time to Maximum Effect of Osteocalcin | 22.0 days |
| Romosozumab 3.0 mg/kg SC | Time to Maximum Effect of Osteocalcin | 22.0 days |
| Romosozumab 5.0 mg/kg SC | Time to Maximum Effect of Osteocalcin | 29.0 days |
| Romosozumab 10.0 mg/kg SC | Time to Maximum Effect of Osteocalcin | 36.0 days |
| Placebo IV | Time to Maximum Effect of Osteocalcin | 34.0 days |
| Romosozumab 1.0 mg/kg IV | Time to Maximum Effect of Osteocalcin | 22.0 days |
| Romosozumab 5.0 mg/kg IV | Time to Maximum Effect of Osteocalcin | 32.5 days |
Secondary
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.
Population: All treated participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo SC | Time to Maximum Effect of P1NP | 39.5 days |
| Romosozumab 0.1 mg/kg SC | Time to Maximum Effect of P1NP | 11.0 days |
| Romosozumab 0.3 mg/kg SC | Time to Maximum Effect of P1NP | 4.5 days |
| Romosozumab 1.0 mg/kg SC | Time to Maximum Effect of P1NP | 15.0 days |
| Romosozumab 3.0 mg/kg SC | Time to Maximum Effect of P1NP | 22.0 days |
| Romosozumab 5.0 mg/kg SC | Time to Maximum Effect of P1NP | 22.0 days |
| Romosozumab 10.0 mg/kg SC | Time to Maximum Effect of P1NP | 25.5 days |
| Placebo IV | Time to Maximum Effect of P1NP | 43.0 days |
| Romosozumab 1.0 mg/kg IV | Time to Maximum Effect of P1NP | 15.0 days |
| Romosozumab 5.0 mg/kg IV | Time to Maximum Effect of P1NP | 18.5 days |
Secondary
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.
Population: All treated participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo SC | Time to Maximum Effect of sCTX | 1.0 days |
| Romosozumab 0.1 mg/kg SC | Time to Maximum Effect of sCTX | 1.0 days |
| Romosozumab 0.3 mg/kg SC | Time to Maximum Effect of sCTX | 1.0 days |
| Romosozumab 1.0 mg/kg SC | Time to Maximum Effect of sCTX | 1.0 days |
| Romosozumab 3.0 mg/kg SC | Time to Maximum Effect of sCTX | 1.0 days |
| Romosozumab 5.0 mg/kg SC | Time to Maximum Effect of sCTX | 8.0 days |
| Romosozumab 10.0 mg/kg SC | Time to Maximum Effect of sCTX | 6.0 days |
| Placebo IV | Time to Maximum Effect of sCTX | 18.5 days |
| Romosozumab 1.0 mg/kg IV | Time to Maximum Effect of sCTX | 1.0 days |
| Romosozumab 5.0 mg/kg IV | Time to Maximum Effect of sCTX | 1.0 days |
Secondary
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.
Population: All treated participants who received subcutaneous romosozumab
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo SC | Time to Maximum Observed Concentration (Tmax) of Romosozumab | 1.5 days |
| Romosozumab 0.1 mg/kg SC | Time to Maximum Observed Concentration (Tmax) of Romosozumab | 2.5 days |
| Romosozumab 0.3 mg/kg SC | Time to Maximum Observed Concentration (Tmax) of Romosozumab | 3 days |
| Romosozumab 1.0 mg/kg SC | Time to Maximum Observed Concentration (Tmax) of Romosozumab | 5 days |
| Romosozumab 3.0 mg/kg SC | Time to Maximum Observed Concentration (Tmax) of Romosozumab | 5 days |
| Romosozumab 5.0 mg/kg SC | Time to Maximum Observed Concentration (Tmax) of Romosozumab | 4.5 days |