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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-004537-28 | EudraCT Number |
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The primary objective of this study was to assess the effects of subcutaneous sumatriptan alone and the effects of a single dose of erenumab (AMG 334) intravenous (IV) and sumatriptan concomitant therapy on resting blood pressure in healthy adults.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Participants received a placebo intravenous (IV) infusion on day 1 then 12 mg subcutaneous sumatriptan on day 2 (Part 1). After a 2-day washout participants received another placebo IV infusion on day 4 followed by 12 mg subcutaneous sumatriptan on day 5 (Part 2). |
|
| Erenumab | Experimental | Participants received a placebo intravenous (IV) infusion on day 1 then 12 mg subcutaneous sumatriptan on day 2 (Part 1). After a 2-day washout participants received 140 mg erenumab IV infusion on day 4 followed by 12 mg subcutaneous sumatriptan on day 5 (Part 2). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Administered by intravenous infusion |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Time-weighted Averages of Mean Arterial Pressure | Mean arterial pressure (MAP) is the average arterial pressure during a single cardiac cycle. MAP was calculated as diastolic blood pressure (DBP) + 0.33 * (systolic blood pressure [SBP]-DBP). Individual time-weighted average in MAP were calculated as area under the measurement-time curve from predose through 2.5 hours of MAP divided by the time period over which the measurements were made (ie, AUCmap0-2.5 hr /2.5 hours). Data were analyzed using a linear mixed effects regression model with fixed effects for treatment and period and random effect for subject; Sumatriptan Alone data include participants from both Groups A (Parts 1 and 2) and B (Part 1 only). | Days 2 and 5 from predose to 2.5 hours after sumatriptan dosing. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events | Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and according to the following: Grade 1 = Mild AE, asymptomatic or mild symptoms; Grade 2 = Moderate, minimal, local or noninvasive intervention indicated; Grade 3 = Severe or medically significant but not immediately life-threatening; Grade 4 = Life-threatening consequences, urgent intervention indicated; Grade 5 = Death related to AE. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Leuven | 3000 | Belgium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29783863 | Background | de Hoon J, Van Hecken A, Vandermeulen C, Herbots M, Kubo Y, Lee E, Eisele O, Vargas G, Gabriel K. Phase 1, randomized, parallel-group, double-blind, placebo-controlled trial to evaluate the effects of erenumab (AMG 334) and concomitant sumatriptan on blood pressure in healthy volunteers. Cephalalgia. 2019 Jan;39(1):100-110. doi: 10.1177/0333102418776017. Epub 2018 May 21. |
| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
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Eligible participants were randomized on day 1 to receive either erenumab or matching placebo in a 2:1 allocation ratio.
This study was conducted at 1 center in Belgium; participants were enrolled from 22 February 2016 to 11 May 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | Group A: Placebo + Sumatriptan | Participants received a placebo intravenous (IV) infusion on day 1 then 12 mg subcutaneous (SC) sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 2 (Part 1). After a 2-day washout participants received another placebo IV infusion on day 4 followed by 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 5 (Part 2). |
| FG001 | Group B: Erenumab + Sumatriptan | Participants received a placebo IV infusion on day 1 then 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 2 (Part 1). After a 2-day washout participants received 140 mg erenumab IV infusion on day 4 followed by 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 5 (Part 2). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Group A: Placebo + Sumatriptan | Participants received a placebo intravenous (IV) infusion on day 1 then 12 mg subcutaneous (SC) sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 2 (Part 1). After a 2-day washout participants received another placebo IV infusion on day 4 followed by 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 5 (Part 2). |
| Units | Counts |
|---|---|
| Participants |
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| 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 | Time-weighted Averages of Mean Arterial Pressure | Mean arterial pressure (MAP) is the average arterial pressure during a single cardiac cycle. MAP was calculated as diastolic blood pressure (DBP) + 0.33 * (systolic blood pressure [SBP]-DBP). Individual time-weighted average in MAP were calculated as area under the measurement-time curve from predose through 2.5 hours of MAP divided by the time period over which the measurements were made (ie, AUCmap0-2.5 hr /2.5 hours). Data were analyzed using a linear mixed effects regression model with fixed effects for treatment and period and random effect for subject; Sumatriptan Alone data include participants from both Groups A (Parts 1 and 2) and B (Part 1 only). | All participants who received at least 1 dose of study drug (placebo, sumatriptan, or erenumab) and with available data. | Posted | Least Squares Mean | Standard Error | mmHg | Days 2 and 5 from predose to 2.5 hours after sumatriptan dosing. |
|
From the first dose of study drug (sumatriptan, placebo or erenumab) until 84 days after the last dose (89 days). Part 1 includes AEs from day 1 to predose on day 4 and Part 2 includes AEs from day 4 through day 89.
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 | Part 1 Group A: Placebo + Sumatriptan | In Part 1 participants in Group A received a placebo IV infusion on day 1 then 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 2. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 19.1 | 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 |
|---|---|
| D018170 | Sumatriptan |
| C000605816 | erenumab |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 |
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| Sumatriptan |
| Drug |
Administered by two 6 mg subcutaneous injections 1 hour apart on day 2 and day 5 |
|
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| Erenumab | Drug | Administered by intravenous infusion |
|
|
| From the first dose of study drug (sumatriptan, placebo or erenumab) until 84 days after the last dose (89 days). Part 1 includes AEs from day 1 to predose on day 4 and Part 2 includes AEs from day 4 through day 89. |
| Area Under the Concentration-time Curve From Time 0 to 6 Hours for Sumatriptan | Plasma concentrations of sumatriptan were quantified using a validated high performance liquid chromatographic method with tandem mass spectrometry detection. Area under the plasma concentration-time curve from time 0 to 6 hours post dose (AUC6hr) after the 2nd 6 mg dose of sumatriptan was estimated using the linear trapezoidal method. Sumatriptan plasma concentrations below the lower limit of quantification (LLOQ; 0.100 ng/mL) were set to 0 before data analysis. Log-transformed AUC6hr was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect. Sumatriptan Alone data include participants from both Groups A (Parts 1 and 2) and B (Part 1 only). | Day 2 and day 5 at 1 hour (prior to 2nd sumatriptan injection), 1 hour 10 minutes, 1.25, 1.5, 2, 3, 4.5, and 7 hours relative to the first 6 mg dose of sumatriptan. |
| Area Under the Concentration-time Curve From Time 0 to Infinity for Sumatriptan | Plasma concentrations of sumatriptan were quantified using a validated high performance liquid chromatographic method with tandem mass spectrometry detection. The area under the plasma concentration-time curve from time 0 to infinity (AUCinf) after the 2nd 6 mg dose of sumatriptan was estimated as the sum of AUClast and Clast/λz where Clast is the last observed concentration and λz is the first-order terminal rate constant estimated via linear regression of the terminal log-linear decay phase. Sumatriptan plasma concentrations below the lower limit of quantification (LLOQ) (0.100 ng/mL) were set to 0 before data analysis. Log-transformed AUCinf was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect. Sumatriptan Alone data include participants from both Groups A (Parts 1 and 2) and B (Part 1 only). | Day 2 and day 5 at 1 hour (prior to 2nd sumatriptan injection), 1 hour 10 minutes, 1.25, 1.5, 2, 3, 4.5, and 7 hours relative to the first 6 mg dose of sumatriptan. |
| Maximum Observed Plasma Concentration (Cmax) of Sumatriptan | Plasma concentrations of sumatriptan were quantified using a validated high performance liquid chromatographic method with tandem mass spectrometry detection. Sumatriptan plasma concentrations below the lower limit of quantification (LLOQ) (0.100 ng/mL) were set to 0 before data analysis. Log-transformed maximum observed plasma concentration (Cmax) was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect. Sumatriptan Alone data include participants from both Groups A (Parts 1 and 2) and B (Part 1 only). | Day 2 and day 5 at predose, 1 hour (prior to 2nd sumatriptan injection), 1 hour 10 minutes, 1.25, 1.5, 2, 3, 4.5, and 7 hours relative to the first 6 mg dose of sumatriptan. |
| Number of Participants Who Developed Anti-erenumab Antibodies | Two validated assays were used to detect the presence of anti-erenumab antibodies. All samples were first tested in an electrochemiluminescence-based bridging assay to detect antibodies capable of binding to erenumab (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a cell-based assay to determine neutralizing activity against erenumab (Neutralizing Antibody Assay). If a post-dose sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the sample was defined as positive for neutralizing antibodies. Binding/neutralizing antibody positive is defined as participants with an antibody positive postbaseline results and with a negative or no result at baseline. | Baseline and day 89 |
| BG001 | Group B: Erenumab + Sumatriptan | Participants received a placebo IV infusion on day 1 then 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 2 (Part 1). After a 2-day washout participants received 140 mg erenumab IV infusion on day 4 followed by 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 5 (Part 2). |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Age, Customized | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
All participants who received placebo and sumatriptan (Group A, Parts 1 and 2 and Group B, Part 1). |
| OG001 | Erenumab + Sumatriptan | All participants who received erenumab plus sumatriptan (Group B, Part 2) |
|
|
|
| Secondary | Number of Participants With Adverse Events | Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and according to the following: Grade 1 = Mild AE, asymptomatic or mild symptoms; Grade 2 = Moderate, minimal, local or noninvasive intervention indicated; Grade 3 = Severe or medically significant but not immediately life-threatening; Grade 4 = Life-threatening consequences, urgent intervention indicated; Grade 5 = Death related to AE. | All participants who received at least 1 dose of study drug (placebo, sumatriptan, or erenumab). | Posted | Count of Participants | Participants | From the first dose of study drug (sumatriptan, placebo or erenumab) until 84 days after the last dose (89 days). Part 1 includes AEs from day 1 to predose on day 4 and Part 2 includes AEs from day 4 through day 89. |
|
|
|
| Secondary | Area Under the Concentration-time Curve From Time 0 to 6 Hours for Sumatriptan | Plasma concentrations of sumatriptan were quantified using a validated high performance liquid chromatographic method with tandem mass spectrometry detection. Area under the plasma concentration-time curve from time 0 to 6 hours post dose (AUC6hr) after the 2nd 6 mg dose of sumatriptan was estimated using the linear trapezoidal method. Sumatriptan plasma concentrations below the lower limit of quantification (LLOQ; 0.100 ng/mL) were set to 0 before data analysis. Log-transformed AUC6hr was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect. Sumatriptan Alone data include participants from both Groups A (Parts 1 and 2) and B (Part 1 only). | All participants who received at least 1 dose of study drug (placebo, sumatriptan, or erenumab) and have at least one pharmacokinetic (PK) sample collected or one PK parameter. | Posted | Geometric Least Squares Mean | Standard Error | hr*ng/mL | Day 2 and day 5 at 1 hour (prior to 2nd sumatriptan injection), 1 hour 10 minutes, 1.25, 1.5, 2, 3, 4.5, and 7 hours relative to the first 6 mg dose of sumatriptan. |
|
|
|
|
| Secondary | Area Under the Concentration-time Curve From Time 0 to Infinity for Sumatriptan | Plasma concentrations of sumatriptan were quantified using a validated high performance liquid chromatographic method with tandem mass spectrometry detection. The area under the plasma concentration-time curve from time 0 to infinity (AUCinf) after the 2nd 6 mg dose of sumatriptan was estimated as the sum of AUClast and Clast/λz where Clast is the last observed concentration and λz is the first-order terminal rate constant estimated via linear regression of the terminal log-linear decay phase. Sumatriptan plasma concentrations below the lower limit of quantification (LLOQ) (0.100 ng/mL) were set to 0 before data analysis. Log-transformed AUCinf was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect. Sumatriptan Alone data include participants from both Groups A (Parts 1 and 2) and B (Part 1 only). | All participants who received at least 1 dose of study drug (placebo, sumatriptan, or erenumab) and have at least one pharmacokinetic (PK) sample collected or one PK parameter. | Posted | Geometric Least Squares Mean | Standard Error | hr*ng/mL | Day 2 and day 5 at 1 hour (prior to 2nd sumatriptan injection), 1 hour 10 minutes, 1.25, 1.5, 2, 3, 4.5, and 7 hours relative to the first 6 mg dose of sumatriptan. |
|
|
|
|
| Secondary | Maximum Observed Plasma Concentration (Cmax) of Sumatriptan | Plasma concentrations of sumatriptan were quantified using a validated high performance liquid chromatographic method with tandem mass spectrometry detection. Sumatriptan plasma concentrations below the lower limit of quantification (LLOQ) (0.100 ng/mL) were set to 0 before data analysis. Log-transformed maximum observed plasma concentration (Cmax) was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect. Sumatriptan Alone data include participants from both Groups A (Parts 1 and 2) and B (Part 1 only). | All participants who received at least 1 dose of study drug (placebo, sumatriptan, or erenumab) and have at least one pharmacokinetic (PK) sample collected or one PK parameter. | Posted | Geometric Least Squares Mean | Standard Error | ng/mL | Day 2 and day 5 at predose, 1 hour (prior to 2nd sumatriptan injection), 1 hour 10 minutes, 1.25, 1.5, 2, 3, 4.5, and 7 hours relative to the first 6 mg dose of sumatriptan. |
|
|
|
|
| Secondary | Number of Participants Who Developed Anti-erenumab Antibodies | Two validated assays were used to detect the presence of anti-erenumab antibodies. All samples were first tested in an electrochemiluminescence-based bridging assay to detect antibodies capable of binding to erenumab (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a cell-based assay to determine neutralizing activity against erenumab (Neutralizing Antibody Assay). If a post-dose sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the sample was defined as positive for neutralizing antibodies. Binding/neutralizing antibody positive is defined as participants with an antibody positive postbaseline results and with a negative or no result at baseline. | Participants who received at least 1 dose of study drug (placebo, sumatriptan, or erenumab) with a postbaseline antibody result. | Posted | Count of Participants | Participants | Baseline and day 89 |
|
|
|
| 0 |
| 12 |
| 11 |
| 12 |
| EG001 | Part 1 Group B: Placebo + Sumatriptan | In Part 1 participants in Group B received a placebo IV infusion on day 1 then 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 2. | 0 | 22 | 17 | 22 |
| EG002 | Part 2 Group A: Placebo + Sumatriptan | In Part 2 participants in Group A received another placebo IV infusion on day 4 followed by 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 5. | 0 | 10 | 9 | 10 |
| EG003 | Part 2: Group B: Erenumab + Sumatriptan | In part 2 participants in Group B received 140 mg erenumab IV infusion on day 4 followed by 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 5. | 0 | 20 | 17 | 20 |
| Palpitations | Cardiac disorders | MedDRA 19.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA 19.1 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA 19.1 | Systematic Assessment |
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| Discomfort | General disorders | MedDRA 19.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 19.1 | Systematic Assessment |
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| Feeling hot | General disorders | MedDRA 19.1 | Systematic Assessment |
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| Injection site erythema | General disorders | MedDRA 19.1 | Systematic Assessment |
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| Injection site swelling | General disorders | MedDRA 19.1 | Systematic Assessment |
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| Injection site urticaria | General disorders | MedDRA 19.1 | Systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
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| Viral infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
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| Thermal burn | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
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| Blood potassium increased | Investigations | MedDRA 19.1 | Systematic Assessment |
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| Blood pressure systolic increased | Investigations | MedDRA 19.1 | Systematic Assessment |
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| Electrocardiogram PR prolongation | Investigations | MedDRA 19.1 | Systematic Assessment |
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| Limb discomfort | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| Burning sensation | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
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| Head discomfort | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA 19.1 | Systematic Assessment |
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| Leukocyturia | Renal and urinary disorders | MedDRA 19.1 | Systematic Assessment |
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| Pharyngeal paraesthesia | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
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| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
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| Throat tightness | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
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| Raynaud's phenomenon | Vascular disorders | MedDRA 19.1 | 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.
| Sulfur Compounds |
| D014363 | Tryptamines |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| Adverse event ≥ grade 2 |
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| Adverse event ≥ grade 3 |
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| Adverse event ≥ grade 4 |
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| Serious adverse events |
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| AE leading to discontinuation of study drug |
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| Fatal adverse events |
|