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The primary objective was to evaluate the safety and tolerability of denosumab (AMG 162) after a single subcutaneous administration in Japanese postmenopausal women.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Participants received a single subcutaneous injection of placebo to denosumab on day 1. |
|
| Denosumab | Experimental | Participants received a single subcutaneous dose of denosumab on day 1. Doses included 0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Administered by subcutaneous injection |
| |
| Denosumab |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events | From day 1 up to 4 months for participants assigned to the 0.03 or 0.1 mg/kg dose cohorts, up to 6 months for participants assigned to the 0.3 mg/kg dose cohort and for up to 9 months for participants assigned to the 1.0 or 3.0 mg/kg dose cohorts |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Serum Concentration Time Curve From Time 0 to Time of Last Quantifiable Serum Concentration (AUC0-t) of Denosumab | Day 1 predose and 5 minutes, 1, 4, 8, 12, 24, hours, days 3, 4, 5, 6, 8, 11, 15, 22, 29, 43, 57, 71, 85, 99, 113, also days 141 and 169 for participants in the 0.3, 1.0, or 3.0 mg/kg cohorts and days 197, 225, and 253 for the 1.0 or 3.0 mg/kg dose cohorts | |
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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 |
|---|---|---|---|
| 21871589 | Background | Kumagai Y, Hasunuma T, Padhi D. A randomized, double-blind, placebo-controlled, single-dose study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of denosumab administered subcutaneously to postmenopausal Japanese women. Bone. 2011 Nov;49(5):1101-7. doi: 10.1016/j.bone.2011.08.007. Epub 2011 Aug 12. |
| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
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The study consisted of 5 dose cohorts of 8 participants. Within each dose cohort 6 participants were randomly assigned to receive denosumab and 2 participants to receive placebo.
This study was conducted at one clinical center in Japan.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants received a single subcutaneous injection of placebo to denosumab on day 1. |
| FG001 | Denosumab 0.03 mg/kg | Participants received a single subcutaneous injection of 0.03 mg/kg denosumab on day 1. |
| FG002 | Denosumab 0.1 mg/kg | Participants received a single subcutaneous injection of 0.1 mg/kg denosumab on day 1. |
| FG003 | Denosumab 0.3 mg/kg | Participants received a single subcutaneous injection of 0.3 mg/kg denosumab on day 1. |
| FG004 | Denosumab 1.0 mg/kg | Participants received a single subcutaneous injection of 1.0 mg/kg denosumab on day 1. |
| FG005 | Denosumab 3.0 mg/kg | Participants received a single subcutaneous injection of 3.0 mg/kg denosumab on day 1. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
All enrolled participants
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants received a single subcutaneous injection of placebo to denosumab on day 1. |
| BG001 | Denosumab 0.03 mg/kg | Participants received a single subcutaneous injection of 0.03 mg/kg denosumab 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, 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 | All treated participants | Posted | Count of Participants | Participants | From day 1 up to 4 months for participants assigned to the 0.03 or 0.1 mg/kg dose cohorts, up to 6 months for participants assigned to the 0.3 mg/kg dose cohort and for up to 9 months for participants assigned to the 1.0 or 3.0 mg/kg dose cohorts |
|
From day 1 up to 4 months for participants assigned to the 0.03 or 0.1 mg/kg dose cohorts, up to 6 months for participants assigned to the 0.3 mg/kg dose cohort and for up to 9 months for participants assigned to the 1.0 or 3.0 mg/kg dose cohorts.
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 | Participants received a single subcutaneous injection of placebo to denosumab on day 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ATRIAL FIBRILLATION | Cardiac disorders | MedDRA 7.1 | 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 |
|---|---|
| D010024 | Osteoporosis |
| ID | Term |
|---|---|
| D001851 | Bone Diseases, Metabolic |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D008659 | Metabolic Diseases |
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| ID | Term |
|---|---|
| D000069448 | Denosumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Biological |
Administered by subcutaneous injection |
|
|
| Maximum Observed Concentration of Denosumab (Cmax) |
| Day 1 predose and 5 minutes, 1, 4, 8, 12, 24, hours, days 3, 4, 5, 6, 8, 11, 15, 22, 29, 43, 57, 71, 85, 99, 113, also days 141 and 169 for participants in the 0.3, 1.0, or 3.0 mg/kg cohorts and days 197, 225, and 253 for the 1.0 or 3.0 mg/kg dose cohorts |
| Time to Maximum Observed Concentration (Tmax) of Denosumab | Day 1 predose and 5 minutes, 1, 4, 8, 12, 24, hours, days 3, 4, 5, 6, 8, 11, 15, 22, 29, 43, 57, 71, 85, 99, 113, also days 141 and 169 for participants in the 0.3, 1.0, or 3.0 mg/kg cohorts and days 197, 225, and 253 for the 1.0 or 3.0 mg/kg dose cohorts |
| Apparent Clearance (CL/F) of Denosumab | Day 1 predose and 5 minutes, 1, 4, 8, 12, 24, hours, days 3, 4, 5, 6, 8, 11, 15, 22, 29, 43, 57, 71, 85, 99, 113, also days 141 and 169 for participants in the 0.3, 1.0, or 3.0 mg/kg cohorts and days 197, 225, and 253 for the 1.0 or 3.0 mg/kg dose cohorts |
| Mean Residence Time (MRT) From Time 0 to Time of Last Quantifiable Serum Concentration | Day 1 predose and 5 minutes, 1, 4, 8, 12, 24, hours, days 3, 4, 5, 6, 8, 11, 15, 22, 29, 43, 57, 71, 85, 99, 113, also days 141 and 169 for participants in the 0.3, 1.0, or 3.0 mg/kg cohorts and days 197, 225, and 253 for the 1.0 or 3.0 mg/kg dose cohorts |
| Percent Change From Baseline in Urinary N-Telopeptide Corrected for Urine Creatinine (N-Tx/Cr) | Baseline and day 2, 3, 4, 5, 6, 8, 11, 15, 22, 29, 43, 57, 71, 85, 99, 113 (for all dose cohorts), 141, 169 (0.3, 1.0, and 3.0 mg/kg cohorts only), 197, 225, 253, 281, and 309 (1.0 and 3.0 mg/kg cohorts only). |
| Percent Change From Baseline in Bone-Specific Alkaline Phosphatase (BSAP) | Baseline and day 8, 15, 22, 29, 43, 57, 71, 85, 99, 113 (for all dose cohorts), 141, 169 (0.3, 1.0, and 3.0 mg/kg cohorts only), 197, 225, and 253, 281, and 309 (1.0 and 3.0 mg/kg cohorts only) |
| Percent Change From Baseline in Intact Parathyroid Hormone (iPTH) | Baseline and day 2, 3, 5, 8, 15, 29, 57, 85, 99, 113 (for all dose cohorts), 141, 169 (0.3, 1.0, and 3.0 mg/kg cohorts only), 197, 225, 253, 281, and 309 (1.0 and 3.0 mg/kg cohorts only) |
| BG002 | Denosumab 0.1 mg/kg | Participants received a single subcutaneous injection of 0.1 mg/kg denosumab on day 1. |
| BG003 | Denosumab 0.3 mg/kg | Participants received a single subcutaneous injection of 0.3 mg/kg denosumab on day 1. |
| BG004 | Denosumab 1.0 mg/kg | Participants received a single subcutaneous injection of 1.0 mg/kg denosumab on day 1. |
| BG005 | Denosumab 3.0 mg/kg | Participants received a single subcutaneous injection of 3.0 mg/kg denosumab on day 1. |
| BG006 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| OG002 |
| Denosumab 0.1 mg/kg |
Participants received a single subcutaneous injection of 0.1 mg/kg denosumab on day 1. |
| OG003 | Denosumab 0.3 mg/kg | Participants received a single subcutaneous injection of 0.3 mg/kg denosumab on day 1. |
| OG004 | Denosumab 1.0 mg/kg | Participants received a single subcutaneous injection of 1.0 mg/kg denosumab on day 1. |
| OG005 | Denosumab 3.0 mg/kg | Participants received a single subcutaneous injection of 3.0 mg/kg denosumab on day 1. |
|
|
| Secondary | Area Under the Serum Concentration Time Curve From Time 0 to Time of Last Quantifiable Serum Concentration (AUC0-t) of Denosumab | All participants who received denosumab | Posted | Mean | Standard Deviation | μg*day/mL | Day 1 predose and 5 minutes, 1, 4, 8, 12, 24, hours, days 3, 4, 5, 6, 8, 11, 15, 22, 29, 43, 57, 71, 85, 99, 113, also days 141 and 169 for participants in the 0.3, 1.0, or 3.0 mg/kg cohorts and days 197, 225, and 253 for the 1.0 or 3.0 mg/kg dose cohorts |
|
|
|
| Secondary | Maximum Observed Concentration of Denosumab (Cmax) | Posted | Mean | Standard Deviation | ng/mL | Day 1 predose and 5 minutes, 1, 4, 8, 12, 24, hours, days 3, 4, 5, 6, 8, 11, 15, 22, 29, 43, 57, 71, 85, 99, 113, also days 141 and 169 for participants in the 0.3, 1.0, or 3.0 mg/kg cohorts and days 197, 225, and 253 for the 1.0 or 3.0 mg/kg dose cohorts |
|
|
|
| Secondary | Time to Maximum Observed Concentration (Tmax) of Denosumab | All participants who received denosumab | Posted | Median | Full Range | days | Day 1 predose and 5 minutes, 1, 4, 8, 12, 24, hours, days 3, 4, 5, 6, 8, 11, 15, 22, 29, 43, 57, 71, 85, 99, 113, also days 141 and 169 for participants in the 0.3, 1.0, or 3.0 mg/kg cohorts and days 197, 225, and 253 for the 1.0 or 3.0 mg/kg dose cohorts |
|
|
|
| Secondary | Apparent Clearance (CL/F) of Denosumab | All participants who received denosumab | Posted | Mean | Standard Deviation | mL/day/kg | Day 1 predose and 5 minutes, 1, 4, 8, 12, 24, hours, days 3, 4, 5, 6, 8, 11, 15, 22, 29, 43, 57, 71, 85, 99, 113, also days 141 and 169 for participants in the 0.3, 1.0, or 3.0 mg/kg cohorts and days 197, 225, and 253 for the 1.0 or 3.0 mg/kg dose cohorts |
|
|
|
| Secondary | Mean Residence Time (MRT) From Time 0 to Time of Last Quantifiable Serum Concentration | All participants who received denosumab | Posted | Mean | Standard Deviation | days | Day 1 predose and 5 minutes, 1, 4, 8, 12, 24, hours, days 3, 4, 5, 6, 8, 11, 15, 22, 29, 43, 57, 71, 85, 99, 113, also days 141 and 169 for participants in the 0.3, 1.0, or 3.0 mg/kg cohorts and days 197, 225, and 253 for the 1.0 or 3.0 mg/kg dose cohorts |
|
|
|
| Secondary | Percent Change From Baseline in Urinary N-Telopeptide Corrected for Urine Creatinine (N-Tx/Cr) | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and day 2, 3, 4, 5, 6, 8, 11, 15, 22, 29, 43, 57, 71, 85, 99, 113 (for all dose cohorts), 141, 169 (0.3, 1.0, and 3.0 mg/kg cohorts only), 197, 225, 253, 281, and 309 (1.0 and 3.0 mg/kg cohorts only). |
|
|
|
| Secondary | Percent Change From Baseline in Bone-Specific Alkaline Phosphatase (BSAP) | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and day 8, 15, 22, 29, 43, 57, 71, 85, 99, 113 (for all dose cohorts), 141, 169 (0.3, 1.0, and 3.0 mg/kg cohorts only), 197, 225, and 253, 281, and 309 (1.0 and 3.0 mg/kg cohorts only) |
|
|
|
| Secondary | Percent Change From Baseline in Intact Parathyroid Hormone (iPTH) | Treated participants with available data at each time point | Posted | Mean | Standard Error | percent change | Baseline and day 2, 3, 5, 8, 15, 29, 57, 85, 99, 113 (for all dose cohorts), 141, 169 (0.3, 1.0, and 3.0 mg/kg cohorts only), 197, 225, 253, 281, and 309 (1.0 and 3.0 mg/kg cohorts only) |
|
|
|
| 0 |
| 10 |
| 6 |
| 10 |
| EG001 | Denosumab 0.03 mg/kg | Participants received a single subcutaneous injection of 0.03 mg/kg denosumab on day 1. | 0 | 6 | 2 | 6 |
| EG002 | Denosumab 0.1 mg/kg | Participants received a single subcutaneous injection of 0.1 mg/kg denosumab on day 1. | 0 | 6 | 3 | 6 |
| EG003 | Denosumab 0.3 mg/kg | Participants received a single subcutaneous injection of 0.3 mg/kg denosumab on day 1. | 0 | 6 | 5 | 6 |
| EG004 | Denosumab 1.0 mg/kg | Participants received a single subcutaneous injection of 1.0 mg/kg denosumab on day 1. | 0 | 6 | 6 | 6 |
| EG005 | Denosumab 3.0 mg/kg | Participants received a single subcutaneous injection of 3.0 mg/kg denosumab on day 1. | 0 | 6 | 5 | 6 |
| EG006 | Denosumab Total | All participants received a single subcutaneous injection of denosumab on day 1. | 0 | 30 | 21 | 30 |
| SENSATION OF BLOCK IN EAR | Ear and labyrinth disorders | MedDRA 7.1 | Systematic Assessment |
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| TINNITUS | Ear and labyrinth disorders | MedDRA 7.1 | Systematic Assessment |
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| BLEPHAROSPASM | Eye disorders | MedDRA 7.1 | Systematic Assessment |
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| CONJUNCTIVAL HAEMORRHAGE | Eye disorders | MedDRA 7.1 | Systematic Assessment |
|
| CONJUNCTIVITIS | Eye disorders | MedDRA 7.1 | Systematic Assessment |
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| ABDOMINAL PAIN | Gastrointestinal disorders | MedDRA 7.1 | Systematic Assessment |
|
| CHEILITIS | Gastrointestinal disorders | MedDRA 7.1 | Systematic Assessment |
|
| DIARRHOEA | Gastrointestinal disorders | MedDRA 7.1 | Systematic Assessment |
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| GASTRITIS | Gastrointestinal disorders | MedDRA 7.1 | Systematic Assessment |
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| GINGIVAL BLEEDING | Gastrointestinal disorders | MedDRA 7.1 | Systematic Assessment |
|
| LIP BLISTER | Gastrointestinal disorders | MedDRA 7.1 | Systematic Assessment |
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| STOMACH DISCOMFORT | Gastrointestinal disorders | MedDRA 7.1 | Systematic Assessment |
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| STOMATITIS | Gastrointestinal disorders | MedDRA 7.1 | Systematic Assessment |
|
| CHEST DISCOMFORT | General disorders | MedDRA 7.1 | Systematic Assessment |
|
| CHEST PAIN | General disorders | MedDRA 7.1 | Systematic Assessment |
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| FATIGUE | General disorders | MedDRA 7.1 | Systematic Assessment |
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| INJECTION SITE ERYTHEMA | General disorders | MedDRA 7.1 | Systematic Assessment |
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| INJECTION SITE HAEMORRHAGE | General disorders | MedDRA 7.1 | Systematic Assessment |
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| INJECTION SITE PAIN | General disorders | MedDRA 7.1 | Systematic Assessment |
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| MALAISE | General disorders | MedDRA 7.1 | Systematic Assessment |
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| SEASONAL ALLERGY | Immune system disorders | MedDRA 7.1 | Systematic Assessment |
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| BRONCHITIS ACUTE | Infections and infestations | MedDRA 7.1 | Systematic Assessment |
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| HERPES ZOSTER | Infections and infestations | MedDRA 7.1 | Systematic Assessment |
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| NASOPHARYNGITIS | Infections and infestations | MedDRA 7.1 | Systematic Assessment |
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| PERIODONTAL INFECTION | Infections and infestations | MedDRA 7.1 | Systematic Assessment |
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| BLISTER | Injury, poisoning and procedural complications | MedDRA 7.1 | Systematic Assessment |
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| CONTUSION | Injury, poisoning and procedural complications | MedDRA 7.1 | Systematic Assessment |
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| THERMAL BURN | Injury, poisoning and procedural complications | MedDRA 7.1 | Systematic Assessment |
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| HEPATIC ENZYME INCREASED | Investigations | MedDRA 7.1 | Systematic Assessment |
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| ARTHRALGIA | Musculoskeletal and connective tissue disorders | MedDRA 7.1 | Systematic Assessment |
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| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA 7.1 | Systematic Assessment |
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| MUSCLE FATIGUE | Musculoskeletal and connective tissue disorders | MedDRA 7.1 | Systematic Assessment |
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| MYALGIA | Musculoskeletal and connective tissue disorders | MedDRA 7.1 | Systematic Assessment |
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| PERIARTHRITIS | Musculoskeletal and connective tissue disorders | MedDRA 7.1 | Systematic Assessment |
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| SPONDYLOSIS | Musculoskeletal and connective tissue disorders | MedDRA 7.1 | Systematic Assessment |
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| DIZZINESS | Nervous system disorders | MedDRA 7.1 | Systematic Assessment |
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| HEADACHE | Nervous system disorders | MedDRA 7.1 | Systematic Assessment |
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| HYPOAESTHESIA | Nervous system disorders | MedDRA 7.1 | Systematic Assessment |
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| RHINITIS ALLERGIC | Respiratory, thoracic and mediastinal disorders | MedDRA 7.1 | Systematic Assessment |
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| RHINORRHOEA | Respiratory, thoracic and mediastinal disorders | MedDRA 7.1 | Systematic Assessment |
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| DERMATITIS | Skin and subcutaneous tissue disorders | MedDRA 7.1 | Systematic Assessment |
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| DERMATITIS CONTACT | Skin and subcutaneous tissue disorders | MedDRA 7.1 | Systematic Assessment |
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| ECZEMA | Skin and subcutaneous tissue disorders | MedDRA 7.1 | Systematic Assessment |
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| HAEMORRHAGE SUBCUTANEOUS | Skin and subcutaneous tissue disorders | MedDRA 7.1 | Systematic Assessment |
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| PRURITUS | Skin and subcutaneous tissue disorders | MedDRA 7.1 | Systematic Assessment |
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| RASH | Skin and subcutaneous tissue disorders | MedDRA 7.1 | Systematic Assessment |
|
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.
| D009750 |
| Nutritional and Metabolic Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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