Osteoporosis
Conditions
Keywords
Osteoporosis, Bone, Renal, Insufficiency, Kidney, Hemodialysis, Impairment
Brief summary
The purpose of this study is to evaluate the safety, tolerability, and immunogenicity profile of romosozumab after a single 210 mg subcutaneous dose in healthy participants and patients with stage 4 renal impairment (RI) or stage 5 RI requiring hemodialysis.
Interventions
DRUGRomosozumab
Administered as three 70 mg/mL prefilled syringe injections
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
- ALL SUBJECTS : * Males or females ≥ 50 years of age * Body weight ≥ 45 and ≤ 110 kg * Willing to adhere to calcium and vitamin D supplementation requirements * Females must be of non-reproductive potential INCLUSION CRITERIA - SUBJECTS WITH RENAL IMPAIRMENT (GROUPS 1 AND 2): * Group 1 - Stage 4 RI (estimated glomerular filtration rate (eGFR) 15-29 mL/min/1.73 m²) * Group 2 - End stage renal disease requiring hemodialysis INCLUSION CRITERIA - HEALTHY SUBJECTS (GROUP 3): • Renal function defined as an estimated glomerular filtration rate (eGFR) ≥ 80 mL/min/1.73 m²
Exclusion criteria
- ALL SUBJECTS: * History of metabolic or bone disease (except for metabolic bone disease in renal impairment (RI) subjects) * History of osteoporosis, vertebral fracture, or fragility fracture of the wrist, humerus, hip, or pelvis after age 50 * Recent bone fracture * Vitamin D insufficiency * Hypocalcemia or hypercalcemia * Hypomagnesemia * Hypophosphatemia * Untreated hyper- or hypothyroidism * Females with a positive pregnancy test * Males with pregnant partners * Females who are lactating/breastfeeding or plan to breastfeed on study and for 3 months after receiving the dose of study drug * History of spinal stenosis * History of facial nerve paralysis * Positive for human immunodeficiency virus (HIV) antibodies * Positive for hepatitis B surface antigen or detectable hepatitis C * Malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical, or breast ductal carcinoma in situ) within 5 years before screening * History of solid organ or bone marrow transplants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit | — |
| Number of Participants With Adverse Events | From the first dose of study drug up to day 85 | A serious adverse event was defined as an adverse event (AE) that met at least 1 of the following serious criteria: * fatal * life-threatening * required in-patient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event. A treatment-related adverse event (TRAE) was an AE assessed by the investigator as possibly related to the study drug, indicated by a yes response to 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 | Baseline and day 85 | Two validated assays were used to detect the presence of anti-romosozumab antibodies. First, an electrochemiluminescent immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding romosozumab. Second, a non-cell-based competitive binding bioassay was used to test positive binding antibody samples for neutralizing activity against romosozumab. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the participant was defined as positive for neutralizing antibodies. |
| Albumin-Adjusted Serum Calcium Concentrations by Visit | Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit | Albumin-adjusted calcium was derived as: Where serum albumin \< 40 g/L then albumin-adjusted calcium = measured total calcium (mmol/L) + 0.02 \* \[40 - serum albumin (g/L)\]; Where serum albumin ≥ 40 g/L then albumin-adjusted calcium = measured total calcium. |
Secondary
| Measure | Time frame |
|---|---|
| Maximum Observed Serum Concentration (Cmax) of Romosozumab | Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85 |
| Time to Maximum Observed Serum Concentration (Tmax) of Romosozumab | Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85 |
| Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85 |
| Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) | Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85 |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 5 centers in the United States. The first participant enrolled on 22 April 2013 and the last participant enrolled on 05 November 2013.
Participants by arm
| Arm | Count |
|---|---|
| Group 1: Stage 4 Renal Impairment Participants with stage 4 renal impairment (defined as an estimated glomerular filtration rate \[eGFR\] 15 to 29 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1. | 8 |
| Group 2: ESRD Requiring Hemodialysis Participants with end stage renal disease (ESRD) requiring hemodialysis received a single subcutaneous injection of 210 mg romosozumab on day 1. | 8 |
| Group 3: Healthy Participants Healthy participants (eGFR ≥ 80 mL/min/1.73 m²) received a single subcutaneous injection of 210 mg romosozumab on day 1. | 8 |
| Total | 24 |
Baseline characteristics
| Characteristic | Group 1: Stage 4 Renal Impairment | Group 2: ESRD Requiring Hemodialysis | Group 3: Healthy Participants | Total |
|---|---|---|---|---|
| Age, Continuous | 66.5 years STANDARD_DEVIATION 8.4 | 65.1 years STANDARD_DEVIATION 6.7 | 63.0 years STANDARD_DEVIATION 8.8 | 64.9 years STANDARD_DEVIATION 7.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 4 Participants | 2 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 4 Participants | 6 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 5 Participants | 7 Participants | 18 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 1 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 8 | 6 / 8 | 0 / 8 |
| serious Total, serious adverse events | 1 / 8 | 1 / 8 | 0 / 8 |
Outcome results
Primary
Albumin-Adjusted Serum Calcium Concentrations by Visit
Albumin-adjusted calcium was derived as: Where serum albumin \< 40 g/L then albumin-adjusted calcium = measured total calcium (mmol/L) + 0.02 \* \[40 - serum albumin (g/L)\]; Where serum albumin ≥ 40 g/L then albumin-adjusted calcium = measured total calcium.
Time frame: Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit
Population: All participants who received study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Stage 4 Renal Impairment | Albumin-Adjusted Serum Calcium Concentrations by Visit | Day 57 | 2.406 mmol/L | Standard Deviation 0.179 |
| Group 1: Stage 4 Renal Impairment | Albumin-Adjusted Serum Calcium Concentrations by Visit | Baseline | 2.452 mmol/L | Standard Deviation 0.228 |
| Group 1: Stage 4 Renal Impairment | Albumin-Adjusted Serum Calcium Concentrations by Visit | Day 8 | 2.355 mmol/L | Standard Deviation 0.187 |
| Group 1: Stage 4 Renal Impairment | Albumin-Adjusted Serum Calcium Concentrations by Visit | Day 15 | 2.378 mmol/L | Standard Deviation 0.146 |
| Group 1: Stage 4 Renal Impairment | Albumin-Adjusted Serum Calcium Concentrations by Visit | Day 22 | 2.329 mmol/L | Standard Deviation 0.151 |
| Group 1: Stage 4 Renal Impairment | Albumin-Adjusted Serum Calcium Concentrations by Visit | Day 29 | 2.338 mmol/L | Standard Deviation 0.162 |
| Group 1: Stage 4 Renal Impairment | Albumin-Adjusted Serum Calcium Concentrations by Visit | Day 43 | 2.404 mmol/L | Standard Deviation 0.2 |
| Group 1: Stage 4 Renal Impairment | Albumin-Adjusted Serum Calcium Concentrations by Visit | End of Study | 2.428 mmol/L | Standard Deviation 0.201 |
| Group 2: ESRD Requiring Hemodialysis | Albumin-Adjusted Serum Calcium Concentrations by Visit | Day 8 | 2.226 mmol/L | Standard Deviation 0.205 |
| Group 2: ESRD Requiring Hemodialysis | Albumin-Adjusted Serum Calcium Concentrations by Visit | Day 43 | 2.209 mmol/L | Standard Deviation 0.169 |
| Group 2: ESRD Requiring Hemodialysis | Albumin-Adjusted Serum Calcium Concentrations by Visit | Day 15 | 2.194 mmol/L | Standard Deviation 0.107 |
| Group 2: ESRD Requiring Hemodialysis | Albumin-Adjusted Serum Calcium Concentrations by Visit | Day 22 | 2.074 mmol/L | Standard Deviation 0.193 |
| Group 2: ESRD Requiring Hemodialysis | Albumin-Adjusted Serum Calcium Concentrations by Visit | Day 29 | 2.166 mmol/L | Standard Deviation 0.258 |
| Group 2: ESRD Requiring Hemodialysis | Albumin-Adjusted Serum Calcium Concentrations by Visit | Day 57 | 2.284 mmol/L | Standard Deviation 0.114 |
| Group 2: ESRD Requiring Hemodialysis | Albumin-Adjusted Serum Calcium Concentrations by Visit | Baseline | 2.379 mmol/L | Standard Deviation 0.131 |
| Group 2: ESRD Requiring Hemodialysis | Albumin-Adjusted Serum Calcium Concentrations by Visit | End of Study | 2.291 mmol/L | Standard Deviation 0.264 |
| Group 3: Healthy Participants | Albumin-Adjusted Serum Calcium Concentrations by Visit | Day 8 | 2.308 mmol/L | Standard Deviation 0.072 |
| Group 3: Healthy Participants | Albumin-Adjusted Serum Calcium Concentrations by Visit | Baseline | 2.340 mmol/L | Standard Deviation 0.057 |
| Group 3: Healthy Participants | Albumin-Adjusted Serum Calcium Concentrations by Visit | Day 57 | 2.319 mmol/L | Standard Deviation 0.07 |
| Group 3: Healthy Participants | Albumin-Adjusted Serum Calcium Concentrations by Visit | Day 15 | 2.293 mmol/L | Standard Deviation 0.07 |
| Group 3: Healthy Participants | Albumin-Adjusted Serum Calcium Concentrations by Visit | Day 43 | 2.320 mmol/L | Standard Deviation 0.065 |
| Group 3: Healthy Participants | Albumin-Adjusted Serum Calcium Concentrations by Visit | Day 29 | 2.316 mmol/L | Standard Deviation 0.062 |
| Group 3: Healthy Participants | Albumin-Adjusted Serum Calcium Concentrations by Visit | Day 22 | 2.311 mmol/L | Standard Deviation 0.104 |
| Group 3: Healthy Participants | Albumin-Adjusted Serum Calcium Concentrations by Visit | End of Study | 2.330 mmol/L | Standard Deviation 0.065 |
Primary
Intact Parathyroid Hormone (iPTH)Concentrations by Visit
Time frame: Baseline, days 8, 15, 22, 29, 43, 57, and 85/end of study visit
Population: All participants who received study drug and with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Stage 4 Renal Impairment | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Baseline | 5.014 pmol/L | Standard Deviation 1.597 |
| Group 1: Stage 4 Renal Impairment | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Day 8 | 9.192 pmol/L | Standard Deviation 3.077 |
| Group 1: Stage 4 Renal Impairment | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Day 15 | 8.887 pmol/L | Standard Deviation 4.743 |
| Group 1: Stage 4 Renal Impairment | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Day 22 | 10.425 pmol/L | Standard Deviation 4.19 |
| Group 1: Stage 4 Renal Impairment | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Day 29 | 12.495 pmol/L | Standard Deviation 5.248 |
| Group 1: Stage 4 Renal Impairment | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Day 43 | 9.921 pmol/L | Standard Deviation 5.906 |
| Group 1: Stage 4 Renal Impairment | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Day 57 | 9.311 pmol/L | Standard Deviation 4.571 |
| Group 1: Stage 4 Renal Impairment | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | End of Study | 6.958 pmol/L | Standard Deviation 3.812 |
| Group 2: ESRD Requiring Hemodialysis | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Day 15 | 17.376 pmol/L | Standard Deviation 10.108 |
| Group 2: ESRD Requiring Hemodialysis | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Day 57 | 17.893 pmol/L | Standard Deviation 11.196 |
| Group 2: ESRD Requiring Hemodialysis | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Day 22 | 29.724 pmol/L | Standard Deviation 20.565 |
| Group 2: ESRD Requiring Hemodialysis | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Day 29 | 29.857 pmol/L | Standard Deviation 20.461 |
| Group 2: ESRD Requiring Hemodialysis | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Day 43 | 21.374 pmol/L | Standard Deviation 14.184 |
| Group 2: ESRD Requiring Hemodialysis | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Baseline | 11.765 pmol/L | Standard Deviation 12.003 |
| Group 2: ESRD Requiring Hemodialysis | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Day 8 | 19.812 pmol/L | Standard Deviation 16.289 |
| Group 2: ESRD Requiring Hemodialysis | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | End of Study | 23.503 pmol/L | Standard Deviation 24.339 |
| Group 3: Healthy Participants | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Day 15 | 6.473 pmol/L | Standard Deviation 3.88 |
| Group 3: Healthy Participants | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Day 8 | 6.776 pmol/L | Standard Deviation 3.612 |
| Group 3: Healthy Participants | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Baseline | 4.682 pmol/L | Standard Deviation 3.432 |
| Group 3: Healthy Participants | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Day 22 | 6.818 pmol/L | Standard Deviation 3.959 |
| Group 3: Healthy Participants | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Day 57 | 5.279 pmol/L | Standard Deviation 2.215 |
| Group 3: Healthy Participants | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Day 43 | 6.508 pmol/L | Standard Deviation 3.289 |
| Group 3: Healthy Participants | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | Day 29 | 7.348 pmol/L | Standard Deviation 3.997 |
| Group 3: Healthy Participants | Intact Parathyroid Hormone (iPTH)Concentrations by Visit | End of Study | 4.457 pmol/L | Standard Deviation 2.506 |
Primary
Number of Participants Who Developed Anti-Romosozumab Antibodies
Two validated assays were used to detect the presence of anti-romosozumab antibodies. First, an electrochemiluminescent immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding romosozumab. Second, a non-cell-based competitive binding bioassay was used to test positive binding antibody samples for neutralizing activity against romosozumab. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the participant was defined as positive for neutralizing antibodies.
Time frame: Baseline and day 85
Population: All participants who received study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: Stage 4 Renal Impairment | Number of Participants Who Developed Anti-Romosozumab Antibodies | Binding antibody positive | 0 Participants |
| Group 1: Stage 4 Renal Impairment | Number of Participants Who Developed Anti-Romosozumab Antibodies | Neutralizing antibody positive | 0 Participants |
| Group 2: ESRD Requiring Hemodialysis | Number of Participants Who Developed Anti-Romosozumab Antibodies | Binding antibody positive | 0 Participants |
| Group 2: ESRD Requiring Hemodialysis | Number of Participants Who Developed Anti-Romosozumab Antibodies | Neutralizing antibody positive | 0 Participants |
| Group 3: Healthy Participants | Number of Participants Who Developed Anti-Romosozumab Antibodies | Binding antibody positive | 1 Participants |
| Group 3: Healthy Participants | Number of Participants Who Developed Anti-Romosozumab Antibodies | Neutralizing antibody positive | 0 Participants |
Primary
Number of Participants With Adverse Events
A serious adverse event was defined as an adverse event (AE) that met at least 1 of the following serious criteria: * fatal * life-threatening * required in-patient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event. A treatment-related adverse event (TRAE) was an AE assessed by the investigator as possibly related to the study drug, indicated by a yes response to the question: Is there a reasonable possibility that the event may have been caused by the investigational product?
Time frame: From the first dose of study drug up to day 85
Population: All participants who received study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: Stage 4 Renal Impairment | Number of Participants With Adverse Events | Treatment-related fatal adverse events | 0 Participants |
| Group 1: Stage 4 Renal Impairment | Number of Participants With Adverse Events | All adverse events | 7 Participants |
| Group 1: Stage 4 Renal Impairment | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Group 1: Stage 4 Renal Impairment | Number of Participants With Adverse Events | AEs leading to discontinuation of study drug | 0 Participants |
| Group 1: Stage 4 Renal Impairment | Number of Participants With Adverse Events | Serious adverse events | 1 Participants |
| Group 1: Stage 4 Renal Impairment | Number of Participants With Adverse Events | Treatment-related adverse events | 5 Participants |
| Group 1: Stage 4 Renal Impairment | Number of Participants With Adverse Events | TRAEs leading to discontinuation of study drug | 0 Participants |
| Group 1: Stage 4 Renal Impairment | Number of Participants With Adverse Events | Treatment-related serious adverse events | 0 Participants |
| Group 2: ESRD Requiring Hemodialysis | Number of Participants With Adverse Events | Serious adverse events | 1 Participants |
| Group 2: ESRD Requiring Hemodialysis | Number of Participants With Adverse Events | Treatment-related serious adverse events | 0 Participants |
| Group 2: ESRD Requiring Hemodialysis | Number of Participants With Adverse Events | All adverse events | 6 Participants |
| Group 2: ESRD Requiring Hemodialysis | Number of Participants With Adverse Events | TRAEs leading to discontinuation of study drug | 0 Participants |
| Group 2: ESRD Requiring Hemodialysis | Number of Participants With Adverse Events | Treatment-related fatal adverse events | 0 Participants |
| Group 2: ESRD Requiring Hemodialysis | Number of Participants With Adverse Events | AEs leading to discontinuation of study drug | 0 Participants |
| Group 2: ESRD Requiring Hemodialysis | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Group 2: ESRD Requiring Hemodialysis | Number of Participants With Adverse Events | Treatment-related adverse events | 6 Participants |
| Group 3: Healthy Participants | Number of Participants With Adverse Events | Treatment-related fatal adverse events | 0 Participants |
| Group 3: Healthy Participants | Number of Participants With Adverse Events | All adverse events | 0 Participants |
| Group 3: Healthy Participants | Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
| Group 3: Healthy Participants | Number of Participants With Adverse Events | AEs leading to discontinuation of study drug | 0 Participants |
| Group 3: Healthy Participants | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Group 3: Healthy Participants | Number of Participants With Adverse Events | Treatment-related adverse events | 0 Participants |
| Group 3: Healthy Participants | Number of Participants With Adverse Events | Treatment-related serious adverse events | 0 Participants |
| Group 3: Healthy Participants | Number of Participants With Adverse Events | TRAEs leading to discontinuation of study drug | 0 Participants |
Secondary
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf)
Time frame: Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
Population: All participants were included in the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Stage 4 Renal Impairment | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) | 642 days*µg/mL | Standard Deviation 221 |
| Group 2: ESRD Requiring Hemodialysis | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) | 447 days*µg/mL | Standard Deviation 154 |
| Group 3: Healthy Participants | Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) | 445 days*µg/mL | Standard Deviation 143 |
Secondary
Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)
Time frame: Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
Population: All participants were included in the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Stage 4 Renal Impairment | Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | 637 days*µg/mL | Standard Deviation 218 |
| Group 2: ESRD Requiring Hemodialysis | Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | 444 days*µg/mL | Standard Deviation 154 |
| Group 3: Healthy Participants | Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | 443 days*µg/mL | Standard Deviation 143 |
Secondary
Maximum Observed Serum Concentration (Cmax) of Romosozumab
Time frame: Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
Population: All participants were included in the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Stage 4 Renal Impairment | Maximum Observed Serum Concentration (Cmax) of Romosozumab | 28.9 µg/mL | Standard Deviation 10.8 |
| Group 2: ESRD Requiring Hemodialysis | Maximum Observed Serum Concentration (Cmax) of Romosozumab | 19.8 µg/mL | Standard Deviation 7.3 |
| Group 3: Healthy Participants | Maximum Observed Serum Concentration (Cmax) of Romosozumab | 22.4 µg/mL | Standard Deviation 10.3 |
Secondary
Time to Maximum Observed Serum Concentration (Tmax) of Romosozumab
Time frame: Pre-dose on day -1 and on days 2, 3, 4, 6, 8, 11, 15, 18, 22, 29, 36, 43, 57 and 85
Population: All participants were included in the analysis
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Group 1: Stage 4 Renal Impairment | Time to Maximum Observed Serum Concentration (Tmax) of Romosozumab | 5.0 days | Full Range 10.8 |
| Group 2: ESRD Requiring Hemodialysis | Time to Maximum Observed Serum Concentration (Tmax) of Romosozumab | 5.0 days | Full Range 7.3 |
| Group 3: Healthy Participants | Time to Maximum Observed Serum Concentration (Tmax) of Romosozumab | 5.0 days | Full Range 10.3 |