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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Participants were randomized to receive a single dose of matching placebo administered by subcutaneous or intravenous injection. |
|
| Romosozumab | Experimental | Participants were randomized to receive a single dose of romosozumab administered by subcutaneous or intravenous injection. The starting dose was 0.1 mg/kg, with sequential escalation up to 10 mg/kg. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Romosozumab | Drug | Administered subcutaneously or intravenously |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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?' | 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. |
| 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. | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | |
| Time to Maximum Observed Concentration (Tmax) of Romosozumab |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20593411 | Background | Padhi D, Jang G, Stouch B, Fang L, Posvar E. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res. 2011 Jan;26(1):19-26. doi: 10.1002/jbmr.173. |
| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo SC | Participants received a single subcutaneous (SC) injection of matching placebo. |
| FG001 | Romosozumab 0.1 mg/kg SC | Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab. |
| FG002 | Romosozumab 0.3 mg/kg SC | Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab. |
| FG003 | Romosozumab 1.0 mg/kg SC | Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab. |
| FG004 | Romosozumab 3.0 mg/kg SC | Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab. |
| FG005 | Romosozumab 5.0 mg/kg SC | Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab. |
| FG006 | Romosozumab 10.0 mg/kg SC | Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab. |
| FG007 | Placebo IV | Participants received a single intravenous (IV) injection of matching placebo. |
| FG008 | Romosozumab 1.0 mg/kg IV | Participants received a single intravenous injection of 1.0 mg/kg romosozumab. |
| FG009 | Romosozumab 5.0 mg/kg IV | Participants received a single intravenous injection of 5.0 mg/kg romosozumab |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
All treated participants
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo SC | Participants received a single subcutaneous (SC) injection of matching placebo. |
| BG001 | Romosozumab 0.1 mg/kg SC | Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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?' | All treated participants | Posted | Count of Participants | Participants | 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. |
|
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.
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo SC | Participants received a single subcutaneous (SC) injection of matching placebo. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| HEPATITIS | Hepatobiliary disorders | MedDRA 17.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA 17.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Amgen Inc. | 866-572-6436 | medinfo@amgen.com |
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| ID | Term |
|---|---|
| D001851 | Bone Diseases, Metabolic |
| ID | Term |
|---|---|
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C557282 | romosozumab |
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| Placebo | Drug | Administered subcutaneously or intravenously |
|
| 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. |
| 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 | 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. | 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 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). | 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 Type 1 Aminoterminal Propeptide (P1NP) | Defined as the maximum value postdose. | 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. |
| Time to Maximum Effect of P1NP | Defined as the time to maximum value postdose. | 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 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) | Defined as the minimum value postdose. | 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. |
| Time to Maximum Effect of sCTX | Defined as the time to minimum value postdose. | 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 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 | Defined as the maximum value postdose. | 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. |
| Time to Maximum Effect of Osteocalcin | Defined as the time to maximum value postdose. | 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) | Defined as the maximum value postdose. | 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. |
| Time to Maximum Effect of BSAP | Defined as the time to maximum value postdose. | 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 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) | Defined as the maximum value postdose. | 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. |
| Time to Maximum Effect of iPTH | Defined as the time to maximum value postdose. | 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 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 |
| BG002 | Romosozumab 0.3 mg/kg SC | Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab. |
| BG003 | Romosozumab 1.0 mg/kg SC | Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab. |
| BG004 | Romosozumab 3.0 mg/kg SC | Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab. |
| BG005 | Romosozumab 5.0 mg/kg SC | Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab. |
| BG006 | Romosozumab 10.0 mg/kg SC | Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab. |
| BG007 | Placebo IV | Participants received a single intravenous (IV) injection of matching placebo. |
| BG008 | Romosozumab 1.0 mg/kg IV | Participants received a single intravenous injection of 1.0 mg/kg romosozumab. |
| BG009 | Romosozumab 5.0 mg/kg IV | Participants received a single intravenous injection of 5.0 mg/kg romosozumab |
| BG010 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
|
Participants received a single subcutaneous (SC) injection of matching placebo. |
| OG001 | Romosozumab 0.1 mg/kg SC | Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab. |
| OG002 | Romosozumab 0.3 mg/kg SC | Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab. |
| OG003 | Romosozumab 1.0 mg/kg SC | Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab. |
| OG004 | Romosozumab 3.0 mg/kg SC | Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab. |
| OG005 | Romosozumab 5.0 mg/kg SC | Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab. |
| OG006 | Romosozumab 10.0 mg/kg SC | Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab. |
| OG007 | Placebo IV | Participants received a single intravenous (IV) injection of matching placebo. |
| OG008 | Romosozumab 1.0 mg/kg IV | Participants received a single intravenous injection of 1.0 mg/kg romosozumab. |
| OG009 | Romosozumab 5.0 mg/kg IV | Participants received a single intravenous injection of 5.0 mg/kg romosozumab |
|
|
| 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. | All treated participants | Posted | Number | participants | 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). |
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| Secondary | Maximum Observed Concentration (Cmax) of Romosozumab | All treated participants who received subcutaneous romosozumab | Posted | Mean | Standard Deviation | ng/mL | 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. |
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| Secondary | Time to Maximum Observed Concentration (Tmax) of Romosozumab | All treated participants who received subcutaneous romosozumab | Posted | Median | Full Range | days | 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. |
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| Secondary | Initial Concentration Following IV Administration (C0) of Romosozumab | All treated participants who received intravenously administered romosozumab | Posted | Mean | Standard Deviation | ng/mL | Day 1 at the end of infusion |
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| Secondary | Area Under the Serum Concentration-time Curve From Time Zero to Infinity for Romosozumab | All treated participants who received romosozumab | Posted | Mean | Standard Deviation | µg*hr/mL | 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. |
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| Secondary | Apparent Clearance (CL/F) / Clearance (CL) for Romosozumab | All treated participants who received romosozumab | Posted | Mean | Standard Deviation | mL/hr/kg | 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. |
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| 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. | All treated participants who received 3, 5, or 10 mg/kg romosozumab | Posted | Mean | Standard Deviation | days | 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. |
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| 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). | All treated participants who received romosozumab | Posted | Mean | Standard Deviation | days | 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. |
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| Secondary | Maximum Effect for Serum Type 1 Aminoterminal Propeptide (P1NP) | Defined as the maximum value postdose. | All treated participants | Posted | Mean | Standard Deviation | ng/mL | 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. |
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| Secondary | Time to Maximum Effect of P1NP | Defined as the time to maximum value postdose. | All treated participants | Posted | Median | Full Range | days | 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. |
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| Secondary | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for P1NP | All treated participants | Posted | Mean | Standard Deviation | days*ng/mL | 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. |
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| Secondary | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for P1NP | All treated participants | Posted | Mean | Standard Deviation | days*ng/mL | 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, |
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| Secondary | Maximum Effect for Serum C-telopeptide (sCTX) | Defined as the minimum value postdose. | All treated participants | Posted | Mean | Standard Deviation | ng/mL | 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. |
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| Secondary | Time to Maximum Effect of sCTX | Defined as the time to minimum value postdose. | All treated participants | Posted | Median | Full Range | days | 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. |
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| Secondary | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for sCTX | All treated participants | Posted | Mean | Standard Deviation | days*ng/mL | 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. |
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| Secondary | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for sCTX | All treated participants | Posted | Mean | Standard Deviation | days*ng/mL | 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. |
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| Secondary | Maximum Effect for Osteocalcin | Defined as the maximum value postdose. | All treated participants | Posted | Mean | Standard Deviation | µg/L | 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. |
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| Secondary | Time to Maximum Effect of Osteocalcin | Defined as the time to maximum value postdose. | All treated participants | Posted | Median | Full Range | days | 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. |
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| Secondary | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for Osteocalcin | All treated participants | Posted | Mean | Standard Deviation | days*µg/L | 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. |
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| Secondary | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for Osteocalcin | All treated participants | Posted | Mean | Standard Deviation | days*µg/L | 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. |
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| Secondary | Maximum Effect for Bone-specific Alkaline Phosphatase (BSAP) | Defined as the maximum value postdose. | All treated participants | Posted | Mean | Standard Deviation | µg/L | 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. |
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| Secondary | Time to Maximum Effect of BSAP | Defined as the time to maximum value postdose. | All treated participants | Posted | Median | Full Range | days | 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. |
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| Secondary | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for BSAP | All treated participants | Posted | Mean | Standard Deviation | days*µg/L | 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. |
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| Secondary | Area Under the Curve From Day 0 to the Last Sampling Time Point (AUC0-t) for BSAP | All treated participants | Posted | Mean | Standard Deviation | days*µg/L | 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. |
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| Secondary | Maximum Effect for Intact Parathyroid Hormone (iPTH) | Defined as the maximum value postdose. | All treated participants | Posted | Mean | Standard Deviation | ng/L | 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. |
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| Secondary | Time to Maximum Effect of iPTH | Defined as the time to maximum value postdose. | All treated participants | Posted | Median | Full Range | days | 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. |
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| Secondary | Area Under the Curve From Day 0 to Day 29 (AUC0-29) for iPTH | All treated participants | Posted | Mean | Standard Deviation | days*ng/L | 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. |
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| Secondary | Area Under the Curve From Day 0 to the Last Sampling Timepoint (AUC0-t) for iPTH | All treated participants | Posted | Mean | Standard Deviation | days*ng/L | 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. |
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| Secondary | Percent Change From Baseline in Sclerostin | 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. | Posted | Mean | Standard Deviation | percent change | Baseline and days 15, 29, 43, 57, 71, and 85 |
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| Secondary | Serum Calcium Over Time | 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. | Posted | Mean | Standard Deviation | mg/dL | 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 |
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| Secondary | Ionized Calcium Over Time | 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. | Posted | Mean | Standard Deviation | mg/dL | 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 |
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| 0 |
| 14 |
| 9 |
| 14 |
| EG001 | Placebo IV | Participants received a single intravenous (IV) injection of matching placebo. | 0 | 4 | 2 | 4 |
| EG002 | Romosozumab 0.1 mg/kg SC | Participants received a single subcutaneous injection of 0.1 mg/kg romosozumab. | 0 | 6 | 4 | 6 |
| EG003 | Romosozumab 0.3 mg/kg SC | Participants received a single subcutaneous injection of 0.3 mg/kg romosozumab. | 0 | 6 | 4 | 6 |
| EG004 | Romosozumab 1.0 mg/kg SC | Participants received a single subcutaneous injection of 1.0 mg/kg romosozumab. | 0 | 9 | 1 | 9 |
| EG005 | Romosozumab 10.0 mg/kg SC | Participants received a single subcutaneous injection of 10.0 mg/kg romosozumab. | 1 | 6 | 5 | 6 |
| EG006 | Romosozumab 3.0 mg/kg SC | Participants received a single subcutaneous injection of 3.0 mg/kg romosozumab. | 0 | 6 | 5 | 6 |
| EG007 | Romosozumab 5.0 mg/kg SC | Participants received a single subcutaneous injection of 5.0 mg/kg romosozumab. | 0 | 9 | 6 | 9 |
| EG008 | Romosozumab 1.0 mg/kg IV | Participants received a single intravenous injection of 1.0 mg/kg romosozumab. | 0 | 6 | 1 | 6 |
| EG009 | Romosozumab 5.0 mg/kg IV | Participants received a single intravenous injection of 5.0 mg/kg romosozumab. | 0 | 6 | 2 | 6 |
| IRON DEFICIENCY ANAEMIA | Blood and lymphatic system disorders | MedDRA 17.0 | Systematic Assessment |
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| BASEDOW'S DISEASE | Endocrine disorders | MedDRA 17.0 | Systematic Assessment |
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| BLEPHARITIS | Eye disorders | MedDRA 17.0 | Systematic Assessment |
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| CONJUNCTIVITIS | Eye disorders | MedDRA 17.0 | Systematic Assessment |
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| ABDOMINAL PAIN | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| ABDOMINAL PAIN UPPER | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| APHTHOUS STOMATITIS | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| CONSTIPATION | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| DIARRHOEA | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| DRY MOUTH | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| DYSPEPSIA | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| LIP DRY | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| NAUSEA | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| ORAL DISCOMFORT | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| VOMITING | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| ASTHENIA | General disorders | MedDRA 17.0 | Systematic Assessment |
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| AXILLARY PAIN | General disorders | MedDRA 17.0 | Systematic Assessment |
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| CHEST PAIN | General disorders | MedDRA 17.0 | Systematic Assessment |
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| INJECTION SITE ERYTHEMA | General disorders | MedDRA 17.0 | Systematic Assessment |
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| INJECTION SITE HAEMORRHAGE | General disorders | MedDRA 17.0 | Systematic Assessment |
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| INJECTION SITE REACTION | General disorders | MedDRA 17.0 | Systematic Assessment |
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| THIRST | General disorders | MedDRA 17.0 | Systematic Assessment |
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| CELLULITIS | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| ESCHERICHIA URINARY TRACT INFECTION | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| GASTROENTERITIS | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| HORDEOLUM | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| NASOPHARYNGITIS | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| TINEA PEDIS | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| UPPER RESPIRATORY TRACT INFECTION | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| URINARY TRACT INFECTION | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| DECREASED APPETITE | Metabolism and nutrition disorders | MedDRA 17.0 | Systematic Assessment |
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| ARTHRALGIA | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| MUSCLE SPASMS | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| MUSCULOSKELETAL CHEST PAIN | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| MUSCULOSKELETAL DISCOMFORT | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| MUSCULOSKELETAL PAIN | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| PAIN IN EXTREMITY | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| DIZZINESS | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| HEADACHE | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| SOMNOLENCE | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| BREAST TENDERNESS | Reproductive system and breast disorders | MedDRA 17.0 | Systematic Assessment |
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| COUGH | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
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| EPISTAXIS | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
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| PHARYNGOLARYNGEAL PAIN | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
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| DERMATITIS | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| DERMATITIS CONTACT | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| HOT FLUSH | Vascular disorders | MedDRA 17.0 | Systematic Assessment |
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The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
| Neutralizing antibody positive |
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| Day 29 |
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| Day 43 |
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| Day 57 |
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| Day 71 |
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| Day 85 |
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| Day 15 |
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| Day 22 |
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| Day 29 |
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| Day 36 |
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| Day 43 |
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| Day 50 |
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| Day 57 |
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| Day 64 |
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| Day 71 |
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| Day 78 |
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| Day 85 |
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| Day 1 Hour 4 |
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| Day 1 Hour 6 |
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| Day 1 Hour 8 |
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| Day 1 Hour 12 |
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| Day 15 |
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| Day 29 |
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| Day 36 |
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| Day 43 |
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| Day 50 |
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| Day 57 |
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| Day 64 |
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| Day 71 |
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| Day 78 |
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| Day 85 |
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