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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Romosozumab | Experimental | Japanese women in cohorts 1, 2, and 4 will receive a single dose of 1, 3, or 5 mg/kg romosozumab. Non-Japanese women in cohort 3 will receive a single dose of 3 mg/kg romosozumab. |
|
| Placebo | Placebo Comparator | Participants will receive a single dose of placebo. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Romosozumab | Drug | Administered by subcutaneous injection |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events | A serious adverse event (SAE) is defined as an adverse event that
| 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. |
| 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. | 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) |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
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| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Japanese Women: Placebo | Japanese participants received a single subcutaneous injection of placebo on day 1. |
| FG001 | Japanese Women: Romosozumab 1 mg/kg | Japanese participants received a single subcutaneous injection of 1 mg/kg romosozumab on day 1. |
| FG002 | Japanese Women: Romosozumab 3 mg/kg | Japanese participants received a single subcutaneous injection of 3 mg/kg romosozumab on day 1. |
| FG003 | Japanese Women: Romosozumab 5 mg/kg | Japanese participants received a single subcutaneous injection of 5 mg/kg romosozumab on day 1. |
| FG004 | Non-Japanese Women: Placebo | Non-Japanese participants received a single subcutaneous injection of placebo on day 1. |
| FG005 | Non-Japanese Women: Romosozumab 3 mg/kg | Non-Japanese participants received a single subcutaneous injection of 3 mg/kg romosozumab on day 1. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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All treated participants
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| ID | Title | Description |
|---|---|---|
| BG000 | Japanese Women: Placebo | Japanese participants received a single subcutaneous injection of placebo on day 1. |
| BG001 | Japanese Women: Romosozumab 1 mg/kg | Japanese participants received a single subcutaneous injection of 1 mg/kg romosozumab on day 1. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | A serious adverse event (SAE) is defined as an adverse event that
| All treated participants | Posted | Count of Participants | Participants | 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. |
|
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
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 | Japanese Women: Placebo | Japanese participants received a single subcutaneous injection of placebo on day 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Amgen Inc. | 866-572-6436 | medinfo@amgen.com |
| 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 by subcutaneous injection |
|
| Percent Change From Baseline in Sclerostin | Baseline and days 12, 29, 43, 57, 71, and 85 |
| 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. | 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. |
| 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. | 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. |
| 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. | 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. |
| 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. | 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. |
| 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. | 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. |
| 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. | 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. |
| 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. | 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. |
| BG002 | Japanese Women: Romosozumab 3 mg/kg | Japanese participants received a single subcutaneous injection of 3 mg/kg romosozumab on day 1. |
| BG003 | Japanese Women: Romosozumab 5 mg/kg | Japanese participants received a single subcutaneous injection of 5 mg/kg romosozumab on day 1. |
| BG004 | Non-Japanese Women: Placebo | Non-Japanese participants received a single subcutaneous injection of placebo on day 1. |
| BG005 | Non-Japanese Women: Romosozumab 3 mg/kg | Non-Japanese participants received a single subcutaneous injection of 3 mg/kg romosozumab on day 1. |
| BG006 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| OG001 | Japanese Women: Romosozumab 1 mg/kg | Japanese participants received a single subcutaneous injection of 1 mg/kg romosozumab on day 1. |
| OG002 | Japanese Women: Romosozumab 3 mg/kg | Japanese participants received a single subcutaneous injection of 3 mg/kg romosozumab on day 1. |
| OG003 | Japanese Women: Romosozumab 5 mg/kg | Japanese participants received a single subcutaneous injection of 5 mg/kg romosozumab on day 1. |
| OG004 | Non-Japanese Women: Placebo | Non-Japanese participants received a single subcutaneous injection of placebo on day 1. |
| OG005 | Non-Japanese Women: Romosozumab 3 mg/kg | Non-Japanese participants received a single subcutaneous injection of 3 mg/kg romosozumab on day 1. |
|
|
| 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. | All treated participants | Posted | Count of Participants | Participants | No | 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) |
|
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| Primary | Serum Calcium Levels | All treated participants; only participants in the 5 mg/kg cohort were assessed at days 71 and 85. | Posted | Mean | Standard Error | mmol/L | Baseline, days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85 |
|
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| Primary | Serum Intact Parathyroid Hormone (iPTH) Levels | All treated participants; only participants in the 5 mg/kg cohort were assessed at days 71 and 85 | Posted | Mean | Standard Error | pmol/L | Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85 |
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| Secondary | Maximum Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | All treated participants | Posted | Mean | Standard Error | percent change | Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85 |
|
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| Secondary | Maximum Percent Change From Baseline in Serum C-telopeptide (CTX) | All treated participants | Posted | Mean | Standard Error | percent change | Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85 |
|
|
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| Secondary | Percent Change From Baseline in Sclerostin | All treated participants; only participants in the 5 mg/kg cohort were assessed at days 71 and 85. | Posted | Mean | Standard Error | percent change | Baseline and days 12, 29, 43, 57, 71, and 85 |
|
|
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| 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. | All treated participants who received romosozumab | Posted | Median | Full Range | days | 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. |
|
|
|
| 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. | All treated participants who received romosozumab | Posted | Mean | Standard Deviation | µg/mL | 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. |
|
|
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| 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. | All treated participants who received romosozumab | Posted | Mean | Standard Deviation | µg*day/mL | 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. |
|
|
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| 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. | All treated participants who received romosozumab | Posted | Mean | Standard Deviation | µg*day/mL | 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. |
|
|
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| 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. | All treated participants who received romosozumab | Posted | Mean | Standard Deviation | mL/day/kg | 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. |
|
|
|
| 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. | All treated participants who received romosozumab with available T1/2,β data | Posted | Mean | Standard Deviation | days | 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. |
|
|
|
| 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. | All treated participants who received romosozumab | Posted | Mean | Standard Deviation | days | 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. |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 6 |
| 6 |
| EG001 | Japanese Women: Romosozumab 1 mg/kg | Japanese participants received a single subcutaneous injection of 1 mg/kg romosozumab on day 1. | 0 | 6 | 0 | 6 | 4 | 6 |
| EG002 | Japanese Women: Romosozumab 3 mg/kg | Japanese participants received a single subcutaneous injection of 3 mg/kg romosozumab on day 1. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG003 | Japanese Women: Romosozumab 5 mg/kg | Japanese participants received a single subcutaneous injection of 5 mg/kg romosozumab on day 1. | 0 | 6 | 0 | 6 | 6 | 6 |
| EG004 | Non-Japanese Women: Placebo | Non-Japanese participants received a single subcutaneous injection of placebo on day 1. | 0 | 2 | 0 | 2 | 2 | 2 |
| EG005 | Non-Japanese Women: Romosozumab 3 mg/kg | Non-Japanese participants received a single subcutaneous injection of 3 mg/kg romosozumab on day 1. | 0 | 4 | 0 | 4 | 4 | 4 |
| Constipation | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Mouth ulceration | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 17.0 | Systematic Assessment |
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| Injection site haematoma | 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 pruritus | General disorders | MedDRA 17.0 | Systematic Assessment |
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| Vessel puncture site haematoma | General disorders | MedDRA 17.0 | Systematic Assessment |
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| Vessel puncture site haemorrhage | General disorders | MedDRA 17.0 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| Herpes virus infection | 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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| Viral infection | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
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| Muscle strain | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
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| Post procedural swelling | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
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| Venomous sting | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
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| Transaminases increased | Investigations | 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 twitching | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue 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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| Vaginal haemorrhage | 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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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| Eye irritation | Eye 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.
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