Osteopenia
Conditions
Keywords
Amgen, Phase 1, Postmenopausal, Japanese
Brief summary
The main purpose of this study is to assess the safety, tolerability and potential immune response to romosozumab following single subcutaneous (SC; injection under the skin) dose administration in healthy postmenopausal Japanese and non-Japanese women.
Interventions
DRUGRomosozumab
Administered by subcutaneous injection
DRUGPlacebo
Administered by subcutaneous injection
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Japanese subjects must be first (4 grandparents, biologic parents and subject born in Japan), second (4 grandparents and biological parents born in Japan) or third (4 grandparents born in Japan) generation Japanese * Body mass index ≤ 25 kg/m², inclusive at screening * Postmenopausal females defined as 12 continuous months of spontaneous amenorrhea confirmed by a serum follicle-stimulating hormone (FSH) result \> 40 mIU/mL, or 6 weeks postsurgical bilateral oophorectomy (with or without hysterectomy) as documented in medical history (verified with an operative note, if available)
Exclusion criteria
* Osteoporosis, as defined by bone mineral density (BMD) T-scores of the lumbar spine (L1-L4) or total evaluable vertebrae (if fewer than L1-L4); or femoral neck ≤ -2.5 * History of vertebral fracture or fragility fracture of the wrist, humerus, hip or pelvis; * Diagnosed with any condition that will affect bone metabolism
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Participants who received a 1 or 3 mg/kg dose (romosozumab or placebo) were followed for 2 months (day 57) after study drug administration and participants who received 5 mg/kg were followed for 3 months (day 85) for safety assessments. | A serious adverse event (SAE) is defined as an adverse event that * is fatal * is life threatening * requires in-patient hospitalization or prolongation of existing hospitalization * results in persistent or significant disability/incapacity * is a congenital anomaly/birth defect * other significant medical hazard. A treatment-related AE is any treatment-emergent AE that per investigator review has a reasonable possibility of being caused by the investigational product. |
| Number of Participants Who Developed Anti-romosozumab Binding Antibodies | Day 29, and end of study (day 57 for participants assigned to 1 or 3 mg/kg romosozumab/placebo or day 85 for participants assigned to 5 mg/kg romosozumab/placebo) | Participants who were negative for anti-romosozumab binding antibodies at baseline with a positive result at any time post-baseline. |
| Serum Calcium Levels | Baseline, days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85 | — |
| Serum Intact Parathyroid Hormone (iPTH) Levels | Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85 | — |
| Maximum Percent Change From Baseline in Serum C-telopeptide (CTX) | Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85 | — |
| Percent Change From Baseline in Sclerostin | Baseline and days 12, 29, 43, 57, 71, and 85 | — |
| Time to Maximum Observed Concentration of Romosozumab | Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo. | Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL. |
| Maximum Observed Concentration of Romosozumab | Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo. | Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL. |
| Area Under the Serum Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Romosozumab | Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo. | Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL. |
| Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for Romosozumab | Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo. | Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL. |
| Apparent Clearance (CL/F) of Romosozumab | Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo. | Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL. |
| Half-life Associated With Beta (Plateau) Phase of Elimination (T1/2,β) for Romosozumab | Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo. | Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL. |
| Half-life Associated With Gamma (Terminal) Phase of Elimination (T1/2,ɣ) for Romosozumab | Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo. | Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL. |
Participant flow
Recruitment details
This study was conducted at 2 study centers in the United States. Eligible participants were healthy, postmenopausal first, second, or third generation Japanese women and non-Japanese women residing in the United States.
Pre-assignment details
Participants were assigned to one of 4 cohorts. In 3 of the cohorts Japanese women were randomized in a 3:1 ratio to receive 1, 3, or 5 mg/kg romosozumab or placebo. In a 4th cohort non-Japanese women were randomized in a 2:1 ratio to receive 3 mg/kg romosozumab or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Japanese Women: Placebo Japanese participants received a single subcutaneous injection of placebo on day 1. | 6 |
| Japanese Women: Romosozumab 1 mg/kg Japanese participants received a single subcutaneous injection of 1 mg/kg romosozumab on day 1. | 6 |
| Japanese Women: Romosozumab 3 mg/kg Japanese participants received a single subcutaneous injection of 3 mg/kg romosozumab on day 1. | 6 |
| Japanese Women: Romosozumab 5 mg/kg Japanese participants received a single subcutaneous injection of 5 mg/kg romosozumab on day 1. | 6 |
| Non-Japanese Women: Placebo Non-Japanese participants received a single subcutaneous injection of placebo on day 1. | 2 |
| Non-Japanese Women: Romosozumab 3 mg/kg Non-Japanese participants received a single subcutaneous injection of 3 mg/kg romosozumab on day 1. | 4 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Japanese Women: Placebo | Japanese Women: Romosozumab 1 mg/kg | Japanese Women: Romosozumab 3 mg/kg | Japanese Women: Romosozumab 5 mg/kg | Non-Japanese Women: Placebo | Non-Japanese Women: Romosozumab 3 mg/kg | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 5 Participants | 6 Participants | 3 Participants | 2 Participants | 4 Participants | 24 Participants |
| Age, Continuous | 60.8 years STANDARD_DEVIATION 5.7 | 59.3 years STANDARD_DEVIATION 4.9 | 61.7 years STANDARD_DEVIATION 3 | 59.7 years STANDARD_DEVIATION 7.7 | 57.5 years STANDARD_DEVIATION 3.5 | 55.0 years STANDARD_DEVIATION 4.8 | 59.5 years STANDARD_DEVIATION 5.3 |
| Race/Ethnicity, Customized Asian | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 1 Participants | 0 Participants | 25 Participants |
| Race/Ethnicity, Customized White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 2 Participants | 4 Participants | 30 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 2 | 0 / 4 |
| other Total, other adverse events | 6 / 6 | 4 / 6 | 3 / 6 | 6 / 6 | 2 / 2 | 4 / 4 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 2 | 0 / 4 |
Outcome results
Primary
Number of Participants Who Developed Anti-romosozumab Binding Antibodies
Participants who were negative for anti-romosozumab binding antibodies at baseline with a positive result at any time post-baseline.
Time frame: Day 29, and end of study (day 57 for participants assigned to 1 or 3 mg/kg romosozumab/placebo or day 85 for participants assigned to 5 mg/kg romosozumab/placebo)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Japanese Women: Placebo | Number of Participants Who Developed Anti-romosozumab Binding Antibodies | 0 Participants |
| Japanese Women: Romosozumab 1 mg/kg | Number of Participants Who Developed Anti-romosozumab Binding Antibodies | 0 Participants |
| Japanese Women: Romosozumab 3 mg/kg | Number of Participants Who Developed Anti-romosozumab Binding Antibodies | 0 Participants |
| Japanese Women: Romosozumab 5 mg/kg | Number of Participants Who Developed Anti-romosozumab Binding Antibodies | 0 Participants |
| Non-Japanese Women: Placebo | Number of Participants Who Developed Anti-romosozumab Binding Antibodies | 0 Participants |
| Non-Japanese Women: Romosozumab 3 mg/kg | Number of Participants Who Developed Anti-romosozumab Binding Antibodies | 0 Participants |
Primary
Number of Participants With Adverse Events
A serious adverse event (SAE) is defined as an adverse event that * is fatal * is life threatening * requires in-patient hospitalization or prolongation of existing hospitalization * results in persistent or significant disability/incapacity * is a congenital anomaly/birth defect * other significant medical hazard. A treatment-related AE is any treatment-emergent AE that per investigator review has a reasonable possibility of being caused by the investigational product.
Time frame: Participants who received a 1 or 3 mg/kg dose (romosozumab or placebo) were followed for 2 months (day 57) after study drug administration and participants who received 5 mg/kg were followed for 3 months (day 85) for safety assessments.
Population: All treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Japanese Women: Placebo | Number of Participants With Adverse Events | AEs leading to discontinuation of study drug | 0 Participants |
| Japanese Women: Placebo | Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
| Japanese Women: Placebo | Number of Participants With Adverse Events | Any adverse event | 6 Participants |
| Japanese Women: Placebo | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Japanese Women: Placebo | Number of Participants With Adverse Events | Treatment-related adverse events | 2 Participants |
| Japanese Women: Romosozumab 1 mg/kg | Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
| Japanese Women: Romosozumab 1 mg/kg | Number of Participants With Adverse Events | AEs leading to discontinuation of study drug | 0 Participants |
| Japanese Women: Romosozumab 1 mg/kg | Number of Participants With Adverse Events | Any adverse event | 4 Participants |
| Japanese Women: Romosozumab 1 mg/kg | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Japanese Women: Romosozumab 1 mg/kg | Number of Participants With Adverse Events | Treatment-related adverse events | 1 Participants |
| Japanese Women: Romosozumab 3 mg/kg | Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
| Japanese Women: Romosozumab 3 mg/kg | Number of Participants With Adverse Events | AEs leading to discontinuation of study drug | 0 Participants |
| Japanese Women: Romosozumab 3 mg/kg | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Japanese Women: Romosozumab 3 mg/kg | Number of Participants With Adverse Events | Treatment-related adverse events | 2 Participants |
| Japanese Women: Romosozumab 3 mg/kg | Number of Participants With Adverse Events | Any adverse event | 3 Participants |
| Japanese Women: Romosozumab 5 mg/kg | Number of Participants With Adverse Events | Treatment-related adverse events | 1 Participants |
| Japanese Women: Romosozumab 5 mg/kg | Number of Participants With Adverse Events | Any adverse event | 6 Participants |
| Japanese Women: Romosozumab 5 mg/kg | Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
| Japanese Women: Romosozumab 5 mg/kg | Number of Participants With Adverse Events | AEs leading to discontinuation of study drug | 0 Participants |
| Japanese Women: Romosozumab 5 mg/kg | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Non-Japanese Women: Placebo | Number of Participants With Adverse Events | AEs leading to discontinuation of study drug | 0 Participants |
| Non-Japanese Women: Placebo | Number of Participants With Adverse Events | Any adverse event | 2 Participants |
| Non-Japanese Women: Placebo | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Non-Japanese Women: Placebo | Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
| Non-Japanese Women: Placebo | Number of Participants With Adverse Events | Treatment-related adverse events | 0 Participants |
| Non-Japanese Women: Romosozumab 3 mg/kg | Number of Participants With Adverse Events | Any adverse event | 4 Participants |
| Non-Japanese Women: Romosozumab 3 mg/kg | Number of Participants With Adverse Events | AEs leading to discontinuation of study drug | 0 Participants |
| Non-Japanese Women: Romosozumab 3 mg/kg | Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
| Non-Japanese Women: Romosozumab 3 mg/kg | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Non-Japanese Women: Romosozumab 3 mg/kg | Number of Participants With Adverse Events | Treatment-related adverse events | 0 Participants |
Primary
Serum Calcium Levels
Time frame: Baseline, days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85
Population: All treated participants; only participants in the 5 mg/kg cohort were assessed at days 71 and 85.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Japanese Women: Placebo | Serum Calcium Levels | Day 43 | 2.35 mmol/L | Standard Error 0.04 |
| Japanese Women: Placebo | Serum Calcium Levels | Baseline | 2.34 mmol/L | Standard Error 0.04 |
| Japanese Women: Placebo | Serum Calcium Levels | Day 4 | 2.32 mmol/L | Standard Error 0.05 |
| Japanese Women: Placebo | Serum Calcium Levels | Day 22 | 2.31 mmol/L | Standard Error 0.03 |
| Japanese Women: Placebo | Serum Calcium Levels | Day 6 | 2.39 mmol/L | Standard Error 0.05 |
| Japanese Women: Placebo | Serum Calcium Levels | Day 8 | 2.39 mmol/L | Standard Error 0.05 |
| Japanese Women: Placebo | Serum Calcium Levels | Day 71 | 2.34 mmol/L | Standard Error 0.01 |
| Japanese Women: Placebo | Serum Calcium Levels | Day 2 | 2.33 mmol/L | Standard Error 0.04 |
| Japanese Women: Placebo | Serum Calcium Levels | Day 85 | 2.29 mmol/L | Standard Error 0.01 |
| Japanese Women: Placebo | Serum Calcium Levels | Day 57 | 2.37 mmol/L | Standard Error 0.03 |
| Japanese Women: Placebo | Serum Calcium Levels | Day 3 | 2.33 mmol/L | Standard Error 0.05 |
| Japanese Women: Placebo | Serum Calcium Levels | Day 12 | 2.35 mmol/L | Standard Error 0.06 |
| Japanese Women: Placebo | Serum Calcium Levels | Day 29 | 2.37 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Calcium Levels | Day 12 | 2.27 mmol/L | Standard Error 0.05 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Calcium Levels | Day 4 | 2.31 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Calcium Levels | Baseline | 2.31 mmol/L | Standard Error 0.04 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Calcium Levels | Day 43 | 2.33 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Calcium Levels | Day 22 | 2.31 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Calcium Levels | Day 57 | 2.32 mmol/L | Standard Error 0.04 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Calcium Levels | Day 2 | 2.34 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Calcium Levels | Day 6 | 2.30 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Calcium Levels | Day 29 | 2.30 mmol/L | Standard Error 0.04 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Calcium Levels | Day 8 | 2.25 mmol/L | Standard Error 0.02 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Calcium Levels | Day 3 | 2.36 mmol/L | Standard Error 0.04 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Day 6 | 2.31 mmol/L | Standard Error 0.04 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Day 12 | 2.33 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Day 8 | 2.31 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Baseline | 2.33 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Day 29 | 2.28 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Day 57 | 2.29 mmol/L | Standard Error 0.04 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Day 2 | 2.31 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Day 3 | 2.31 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Day 22 | 2.28 mmol/L | Standard Error 0.05 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Day 4 | 2.30 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Day 43 | 2.28 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Calcium Levels | Day 85 | 2.35 mmol/L | Standard Error 0.02 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Calcium Levels | Day 29 | 2.30 mmol/L | Standard Error 0.02 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Calcium Levels | Baseline | 2.38 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Calcium Levels | Day 2 | 2.36 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Calcium Levels | Day 3 | 2.38 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Calcium Levels | Day 4 | 2.32 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Calcium Levels | Day 6 | 2.35 mmol/L | Standard Error 0.04 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Calcium Levels | Day 8 | 2.29 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Calcium Levels | Day 12 | 2.28 mmol/L | Standard Error 0.02 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Calcium Levels | Day 22 | 2.25 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Calcium Levels | Day 43 | 2.34 mmol/L | Standard Error 0.04 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Calcium Levels | Day 57 | 2.30 mmol/L | Standard Error 0.03 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Calcium Levels | Day 71 | 2.39 mmol/L | Standard Error 0.02 |
| Non-Japanese Women: Placebo | Serum Calcium Levels | Baseline | 2.28 mmol/L | Standard Error 0.08 |
| Non-Japanese Women: Placebo | Serum Calcium Levels | Day 22 | 2.33 mmol/L | Standard Error 0 |
| Non-Japanese Women: Placebo | Serum Calcium Levels | Day 2 | 2.34 mmol/L | Standard Error 0.04 |
| Non-Japanese Women: Placebo | Serum Calcium Levels | Day 4 | 2.38 mmol/L | Standard Error 0.02 |
| Non-Japanese Women: Placebo | Serum Calcium Levels | Day 3 | 2.34 mmol/L | Standard Error 0.01 |
| Non-Japanese Women: Placebo | Serum Calcium Levels | Day 57 | 2.28 mmol/L | Standard Error 0 |
| Non-Japanese Women: Placebo | Serum Calcium Levels | Day 29 | 2.36 mmol/L | Standard Error 0.04 |
| Non-Japanese Women: Placebo | Serum Calcium Levels | Day 8 | 2.35 mmol/L | Standard Error 0 |
| Non-Japanese Women: Placebo | Serum Calcium Levels | Day 43 | 2.30 mmol/L | Standard Error 0.07 |
| Non-Japanese Women: Placebo | Serum Calcium Levels | Day 6 | 2.28 mmol/L | Standard Error 0.02 |
| Non-Japanese Women: Placebo | Serum Calcium Levels | Day 12 | 2.33 mmol/L | Standard Error 0.03 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Day 57 | 2.31 mmol/L | Standard Error 0.02 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Day 12 | 2.28 mmol/L | Standard Error 0.04 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Day 4 | 2.36 mmol/L | Standard Error 0.04 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Day 3 | 2.43 mmol/L | Standard Error 0.03 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Day 22 | 2.36 mmol/L | Standard Error 0.03 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Day 43 | 2.34 mmol/L | Standard Error 0.01 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Day 2 | 2.40 mmol/L | Standard Error 0.05 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Baseline | 2.45 mmol/L | Standard Error 0.04 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Day 29 | 2.38 mmol/L | Standard Error 0.05 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Day 8 | 2.38 mmol/L | Standard Error 0.03 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Calcium Levels | Day 6 | 2.40 mmol/L | Standard Error 0.03 |
Primary
Serum Intact Parathyroid Hormone (iPTH) Levels
Time frame: Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85
Population: All treated participants; only participants in the 5 mg/kg cohort were assessed at days 71 and 85
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 29 | 4.83 pmol/L | Standard Error 0.99 |
| Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 12 | 5.04 pmol/L | Standard Error 0.95 |
| Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 22 | 4.69 pmol/L | Standard Error 0.74 |
| Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 71 | 3.40 pmol/L | Standard Error 0.85 |
| Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 3 | 4.93 pmol/L | Standard Error 0.71 |
| Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 57 | 3.89 pmol/L | Standard Error 0.84 |
| Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 4 | 4.47 pmol/L | Standard Error 0.84 |
| Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Baseline | 4.47 pmol/L | Standard Error 0.97 |
| Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 6 | 4.21 pmol/L | Standard Error 0.67 |
| Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 85 | 3.02 pmol/L | Standard Error 0.8 |
| Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 43 | 4.61 pmol/L | Standard Error 0.89 |
| Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 8 | 4.19 pmol/L | Standard Error 0.95 |
| Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 2 | 4.51 pmol/L | Standard Error 0.78 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 3 | 4.69 pmol/L | Standard Error 0.69 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Baseline | 4.24 pmol/L | Standard Error 0.7 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 57 | 4.90 pmol/L | Standard Error 0.64 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 8 | 5.91 pmol/L | Standard Error 0.86 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 4 | 5.09 pmol/L | Standard Error 0.69 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 43 | 6.03 pmol/L | Standard Error 0.73 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 12 | 6.42 pmol/L | Standard Error 0.59 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 2 | 4.92 pmol/L | Standard Error 0.78 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 22 | 5.57 pmol/L | Standard Error 0.64 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 29 | 5.02 pmol/L | Standard Error 0.74 |
| Japanese Women: Romosozumab 1 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 6 | 4.97 pmol/L | Standard Error 0.93 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 2 | 5.01 pmol/L | Standard Error 0.47 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 3 | 5.38 pmol/L | Standard Error 0.44 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 12 | 5.46 pmol/L | Standard Error 0.41 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Baseline | 4.93 pmol/L | Standard Error 0.84 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 22 | 6.15 pmol/L | Standard Error 0.56 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 8 | 5.23 pmol/L | Standard Error 0.68 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 6 | 5.75 pmol/L | Standard Error 0.72 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 4 | 5.09 pmol/L | Standard Error 0.23 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 29 | 5.92 pmol/L | Standard Error 0.68 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 43 | 5.27 pmol/L | Standard Error 0.32 |
| Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 57 | 4.87 pmol/L | Standard Error 0.39 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 85 | 3.82 pmol/L | Standard Error 0.58 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Baseline | 3.63 pmol/L | Standard Error 0.62 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 2 | 4.23 pmol/L | Standard Error 0.54 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 3 | 4.58 pmol/L | Standard Error 0.76 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 4 | 5.20 pmol/L | Standard Error 1.13 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 6 | 4.44 pmol/L | Standard Error 0.77 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 8 | 4.79 pmol/L | Standard Error 0.9 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 12 | 5.80 pmol/L | Standard Error 0.61 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 22 | 7.09 pmol/L | Standard Error 0.84 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 29 | 6.14 pmol/L | Standard Error 0.72 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 43 | 5.61 pmol/L | Standard Error 0.84 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 57 | 4.86 pmol/L | Standard Error 0.55 |
| Japanese Women: Romosozumab 5 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 71 | 4.10 pmol/L | Standard Error 0.47 |
| Non-Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 29 | 4.83 pmol/L | Standard Error 2.81 |
| Non-Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 8 | 4.14 pmol/L | Standard Error 1.91 |
| Non-Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 3 | 3.50 pmol/L | Standard Error 1.06 |
| Non-Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 6 | 3.82 pmol/L | Standard Error 1.49 |
| Non-Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 2 | 3.50 pmol/L | Standard Error 1.49 |
| Non-Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 57 | 2.76 pmol/L | Standard Error 0.85 |
| Non-Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 4 | 3.93 pmol/L | Standard Error 1.7 |
| Non-Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 12 | 4.19 pmol/L | Standard Error 1.86 |
| Non-Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Baseline | 3.77 pmol/L | Standard Error 1.65 |
| Non-Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 22 | 5.46 pmol/L | Standard Error 2.71 |
| Non-Japanese Women: Placebo | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 43 | 3.93 pmol/L | Standard Error 1.27 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 22 | 4.62 pmol/L | Standard Error 0.68 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 6 | 3.66 pmol/L | Standard Error 0.66 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 29 | 4.43 pmol/L | Standard Error 0.4 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 4 | 3.55 pmol/L | Standard Error 0.73 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 43 | 3.53 pmol/L | Standard Error 0.35 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 3 | 2.89 pmol/L | Standard Error 0.37 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 2 | 2.57 pmol/L | Standard Error 0.23 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Baseline | 2.73 pmol/L | Standard Error 0.37 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 12 | 4.46 pmol/L | Standard Error 0.64 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 57 | 2.68 pmol/L | Standard Error 0.27 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Serum Intact Parathyroid Hormone (iPTH) Levels | Day 8 | 3.98 pmol/L | Standard Error 0.68 |
Secondary
Apparent Clearance (CL/F) of Romosozumab
Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.
Time frame: Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.
Population: All treated participants who received romosozumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Japanese Women: Placebo | Apparent Clearance (CL/F) of Romosozumab | 18.6 mL/day/kg | Standard Deviation 10 |
| Japanese Women: Romosozumab 1 mg/kg | Apparent Clearance (CL/F) of Romosozumab | 9.27 mL/day/kg | Standard Deviation 2.64 |
| Japanese Women: Romosozumab 3 mg/kg | Apparent Clearance (CL/F) of Romosozumab | 6.98 mL/day/kg | Standard Deviation 2.35 |
| Japanese Women: Romosozumab 5 mg/kg | Apparent Clearance (CL/F) of Romosozumab | 7.91 mL/day/kg | Standard Deviation 2.68 |
Secondary
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for Romosozumab
Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.
Time frame: Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.
Population: All treated participants who received romosozumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Japanese Women: Placebo | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for Romosozumab | 64.7 µg*day/mL | Standard Deviation 26.8 |
| Japanese Women: Romosozumab 1 mg/kg | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for Romosozumab | 347 µg*day/mL | Standard Deviation 90 |
| Japanese Women: Romosozumab 3 mg/kg | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for Romosozumab | 806 µg*day/mL | Standard Deviation 323 |
| Japanese Women: Romosozumab 5 mg/kg | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for Romosozumab | 421 µg*day/mL | Standard Deviation 147 |
Secondary
Area Under the Serum Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Romosozumab
Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.
Time frame: Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.
Population: All treated participants who received romosozumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Japanese Women: Placebo | Area Under the Serum Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Romosozumab | 64.0 µg*day/mL | Standard Deviation 27 |
| Japanese Women: Romosozumab 1 mg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Romosozumab | 344 µg*day/mL | Standard Deviation 90 |
| Japanese Women: Romosozumab 3 mg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Romosozumab | 804 µg*day/mL | Standard Deviation 320 |
| Japanese Women: Romosozumab 5 mg/kg | Area Under the Serum Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Romosozumab | 412 µg*day/mL | Standard Deviation 136 |
Secondary
Half-life Associated With Beta (Plateau) Phase of Elimination (T1/2,β) for Romosozumab
Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.
Time frame: Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.
Population: All treated participants who received romosozumab with available T1/2,β data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Japanese Women: Romosozumab 1 mg/kg | Half-life Associated With Beta (Plateau) Phase of Elimination (T1/2,β) for Romosozumab | 15.1 days | — |
| Japanese Women: Romosozumab 3 mg/kg | Half-life Associated With Beta (Plateau) Phase of Elimination (T1/2,β) for Romosozumab | 16.2 days | Standard Deviation 4.1 |
| Japanese Women: Romosozumab 5 mg/kg | Half-life Associated With Beta (Plateau) Phase of Elimination (T1/2,β) for Romosozumab | 15.3 days | Standard Deviation 6.2 |
Secondary
Half-life Associated With Gamma (Terminal) Phase of Elimination (T1/2,ɣ) for Romosozumab
Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.
Time frame: Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.
Population: All treated participants who received romosozumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Japanese Women: Placebo | Half-life Associated With Gamma (Terminal) Phase of Elimination (T1/2,ɣ) for Romosozumab | 5.82 days | Standard Deviation 1.05 |
| Japanese Women: Romosozumab 1 mg/kg | Half-life Associated With Gamma (Terminal) Phase of Elimination (T1/2,ɣ) for Romosozumab | 6.31 days | Standard Deviation 1.14 |
| Japanese Women: Romosozumab 3 mg/kg | Half-life Associated With Gamma (Terminal) Phase of Elimination (T1/2,ɣ) for Romosozumab | 7.19 days | Standard Deviation 1.55 |
| Japanese Women: Romosozumab 5 mg/kg | Half-life Associated With Gamma (Terminal) Phase of Elimination (T1/2,ɣ) for Romosozumab | 6.81 days | Standard Deviation 2.69 |
Secondary
Maximum Observed Concentration of Romosozumab
Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.
Time frame: Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.
Population: All treated participants who received romosozumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Japanese Women: Placebo | Maximum Observed Concentration of Romosozumab | 4.06 µg/mL | Standard Deviation 1.45 |
| Japanese Women: Romosozumab 1 mg/kg | Maximum Observed Concentration of Romosozumab | 17.1 µg/mL | Standard Deviation 4.7 |
| Japanese Women: Romosozumab 3 mg/kg | Maximum Observed Concentration of Romosozumab | 33.8 µg/mL | Standard Deviation 8.1 |
| Japanese Women: Romosozumab 5 mg/kg | Maximum Observed Concentration of Romosozumab | 18.6 µg/mL | Standard Deviation 1.1 |
Secondary
Maximum Percent Change From Baseline in Serum C-telopeptide (CTX)
Time frame: Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85
Population: All treated participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Japanese Women: Placebo | Maximum Percent Change From Baseline in Serum C-telopeptide (CTX) | -12.64 percent change | Standard Error 1.4 |
| Japanese Women: Romosozumab 1 mg/kg | Maximum Percent Change From Baseline in Serum C-telopeptide (CTX) | -16.19 percent change | Standard Error 7.36 |
| Japanese Women: Romosozumab 3 mg/kg | Maximum Percent Change From Baseline in Serum C-telopeptide (CTX) | -35.92 percent change | Standard Error 1.94 |
| Japanese Women: Romosozumab 5 mg/kg | Maximum Percent Change From Baseline in Serum C-telopeptide (CTX) | -39.17 percent change | Standard Error 5.13 |
| Non-Japanese Women: Placebo | Maximum Percent Change From Baseline in Serum C-telopeptide (CTX) | -25.46 percent change | Standard Error 8.52 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Maximum Percent Change From Baseline in Serum C-telopeptide (CTX) | -43.32 percent change | Standard Error 9.96 |
Secondary
Maximum Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)
Time frame: Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85
Population: All treated participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Japanese Women: Placebo | Maximum Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | 26.85 percent change | Standard Error 6.39 |
| Japanese Women: Romosozumab 1 mg/kg | Maximum Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | 59.23 percent change | Standard Error 12.21 |
| Japanese Women: Romosozumab 3 mg/kg | Maximum Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | 102.57 percent change | Standard Error 18.26 |
| Japanese Women: Romosozumab 5 mg/kg | Maximum Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | 196.37 percent change | Standard Error 29.79 |
| Non-Japanese Women: Placebo | Maximum Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | 8.30 percent change | Standard Error 1.78 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Maximum Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | 164.44 percent change | Standard Error 35.58 |
Secondary
Percent Change From Baseline in Sclerostin
Time frame: Baseline and days 12, 29, 43, 57, 71, and 85
Population: All treated participants; only participants in the 5 mg/kg cohort were assessed at days 71 and 85.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Japanese Women: Placebo | Percent Change From Baseline in Sclerostin | Day 12 | -3.78 percent change | Standard Error 3.72 |
| Japanese Women: Placebo | Percent Change From Baseline in Sclerostin | Day 85 | -27.41 percent change | Standard Error 2.02 |
| Japanese Women: Placebo | Percent Change From Baseline in Sclerostin | Day 71 | -39.80 percent change | Standard Error 3.87 |
| Japanese Women: Placebo | Percent Change From Baseline in Sclerostin | Day 29 | 591.80 percent change | Standard Error 596.47 |
| Japanese Women: Placebo | Percent Change From Baseline in Sclerostin | Day 57 | -17.89 percent change | Standard Error 11.96 |
| Japanese Women: Placebo | Percent Change From Baseline in Sclerostin | Day 43 | -15.43 percent change | Standard Error 11.39 |
| Japanese Women: Romosozumab 1 mg/kg | Percent Change From Baseline in Sclerostin | Day 43 | 467.07 percent change | Standard Error 55.62 |
| Japanese Women: Romosozumab 1 mg/kg | Percent Change From Baseline in Sclerostin | Day 57 | 167.37 percent change | Standard Error 28.33 |
| Japanese Women: Romosozumab 1 mg/kg | Percent Change From Baseline in Sclerostin | Day 12 | 6639.01 percent change | Standard Error 534.5 |
| Japanese Women: Romosozumab 1 mg/kg | Percent Change From Baseline in Sclerostin | Day 29 | 1602.70 percent change | Standard Error 231.77 |
| Japanese Women: Romosozumab 3 mg/kg | Percent Change From Baseline in Sclerostin | Day 43 | 3384.02 percent change | Standard Error 613.99 |
| Japanese Women: Romosozumab 3 mg/kg | Percent Change From Baseline in Sclerostin | Day 12 | 13749.61 percent change | Standard Error 1091.63 |
| Japanese Women: Romosozumab 3 mg/kg | Percent Change From Baseline in Sclerostin | Day 29 | 7667.80 percent change | Standard Error 675.45 |
| Japanese Women: Romosozumab 3 mg/kg | Percent Change From Baseline in Sclerostin | Day 57 | 911.23 percent change | Standard Error 156.09 |
| Japanese Women: Romosozumab 5 mg/kg | Percent Change From Baseline in Sclerostin | Day 85 | 415.38 percent change | Standard Error 243.4 |
| Japanese Women: Romosozumab 5 mg/kg | Percent Change From Baseline in Sclerostin | Day 57 | 2836.61 percent change | Standard Error 1109.97 |
| Japanese Women: Romosozumab 5 mg/kg | Percent Change From Baseline in Sclerostin | Day 43 | 6844.74 percent change | Standard Error 1730.04 |
| Japanese Women: Romosozumab 5 mg/kg | Percent Change From Baseline in Sclerostin | Day 12 | 17028.81 percent change | Standard Error 1875.81 |
| Japanese Women: Romosozumab 5 mg/kg | Percent Change From Baseline in Sclerostin | Day 29 | 12723.54 percent change | Standard Error 2138.65 |
| Japanese Women: Romosozumab 5 mg/kg | Percent Change From Baseline in Sclerostin | Day 71 | 997.02 percent change | Standard Error 532.06 |
| Non-Japanese Women: Placebo | Percent Change From Baseline in Sclerostin | Day 29 | -14.54 percent change | Standard Error 1.78 |
| Non-Japanese Women: Placebo | Percent Change From Baseline in Sclerostin | Day 43 | -9.35 percent change | Standard Error 4.59 |
| Non-Japanese Women: Placebo | Percent Change From Baseline in Sclerostin | Day 57 | -0.41 percent change | Standard Error 12.65 |
| Non-Japanese Women: Placebo | Percent Change From Baseline in Sclerostin | Day 12 | -17.95 percent change | Standard Error 6.38 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Percent Change From Baseline in Sclerostin | Day 29 | 9581.13 percent change | Standard Error 1283.73 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Percent Change From Baseline in Sclerostin | Day 12 | 14652.96 percent change | Standard Error 1349.38 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Percent Change From Baseline in Sclerostin | Day 43 | 4487.33 percent change | Standard Error 1771.3 |
| Non-Japanese Women: Romosozumab 3 mg/kg | Percent Change From Baseline in Sclerostin | Day 57 | 1826.83 percent change | Standard Error 917.98 |
Secondary
Time to Maximum Observed Concentration of Romosozumab
Serum concentrations of romosozumab were measured using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 50 ng/mL.
Time frame: Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.
Population: All treated participants who received romosozumab
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Japanese Women: Placebo | Time to Maximum Observed Concentration of Romosozumab | 5.0 days |
| Japanese Women: Romosozumab 1 mg/kg | Time to Maximum Observed Concentration of Romosozumab | 5.0 days |
| Japanese Women: Romosozumab 3 mg/kg | Time to Maximum Observed Concentration of Romosozumab | 5.0 days |
| Japanese Women: Romosozumab 5 mg/kg | Time to Maximum Observed Concentration of Romosozumab | 5.0 days |