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This is a prospective, multi-center, open-label, randomized, Phase IV exploratory study comparing safety, tolerability, pharmacokinetics, and effectiveness of ACT-385781A and Flolan (epoprostenol sodium) in patients with pulmonary arterial hypertension who are naïve to injectable prostanoid treatment and in need of such treatment. Approximately 30 patients from 8 U.S. clinical sites will be randomized to receive either ACT-385781A or Flolan (2:1 respectively) for 28 days of treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Active Comparator | ACT-385781A (Actelion Epoprostenol) |
|
| 2 | Active Comparator | Flolan® |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ACT-385781A (Actelion Epoprostenol) | Drug | per Prescribing Information |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Dose Normalized Pharmacokinetics of 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha at 2 ng/kg/Min | The plasma concentration for the epoprostenol metabolite 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha was measured at 2 ng/kg/min just prior to the next up-titration. Dose-normalized concentrations are used to summarize the results. | Day 1 |
| Dose Normalized Pharmacokinetics of 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha at 4 ng/kg/Min | The plasma concentration for the epoprostenol metabolite 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha was measured at 4 ng/kg/min just prior to the next up-titration. Dose-normalized concentrations are used to summarize the results. | Day 1 |
| Dose Normalized Pharmacokinetics of 6-keto-Prostacyclin F1alpha at 2 ng/kg/Min | The plasma concentration for the epoprostenol metabolite 6-keto-Prostacyclin F1alpha was measured at 2 ng/kg/min just prior to the next up-titration. Dose-normalized concentrations are used to summarize the results. | Day 1 |
| Dose Normalized Pharmacokinetics of 6-keto-Prostacyclin F1alpha at 4 ng/kg/Min | The plasma concentration for the epoprostenol metabolite 6-keto-Prostacyclin F1alpha was measured at 4 ng/kg/min just prior to the next up-titration. Dose-normalized concentrations are used to summarize the results. | Day 1 |
| Six-minute Walk Distance (6MWD) - Baseline and Day 28 | The 6-minute walk test (6MWT) was to be performed prior to initiating study treatment either during the screening visit or on Day 1 prior to drug initiation, and Day 28 (End of treatment (EOT)). This assessment is a non-encouraged test that measures the distance walked for a duration of 6 minutes. The 6MWD was recorded in the Case Report Form (CRF). |
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Inclusion Criteria:
Male or female subjects aged 18-65 years
Patients with the following types of pulmonary arterial hypertension (PAH) belonging to WHO Group I:
Idiopathic (IPAH)
Heritable (HPAH)
Associated (APAH) with
Patients with PAH in modified NYHA functional class III or IV at the time of enrollment in need of injectable epoprostenol.
Patients must be injectable prostanoid treatment-naïve and either
newly diagnosed and not yet treated with specific PAH therapies or
currently treated with existing background PAH therapy with one or more of the following medications for 90 days prior to enrollment and on a stable dose for 30 days prior to enrollment:
Women of childbearing potential must use a reliable method of contraception.
Exclusion Criteria:
Patients with respiratory and/or cardiovascular distress in need of emergency care including i.v. epoprostenol administration or any vasopressive i.v. drugs
Known pulmonary veno-occlusive disease (PVOD)
Current use of i.v. inotropic agents
Tachycardia with heart rate > 120 beats/min
Pulmonary arterial hypertension related to any condition other than those specified in the inclusion criteria
Known hypersensitivity to the formulations of ACT-385781A or any of its excipients, and Flolan or any of its excipients
Use of inhaled iloprost or treprostinil during the week prior to screening
Cerebrovascular events (e.g., transient ischemic attack or stroke) within 6 months of screening
History of myocardial infarction
History of left-sided heart disease, including any of the following:
Chronic bleeding disorder
Infection(s) within the past month that in the mind of the investigator would contraindicate the use of epoprostenol
Pregnancy or breast-feeding
Participation in another clinical trial, except observational (noninterventional), or receipt of an investigational product within 30 days prior to randomization
Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease
Known concomitant life-threatening disease other than PAH with a life expectancy < 12 months
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| Name | Affiliation | Role |
|---|---|---|
| Wade Benton, PharmD | Actelion | Study Director |
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Up to 14 days screening period.
The study was conducted at seven Pulmonary Hypertension centers in the U.S. Patients were recruited from these Pulmonary Hypertension medical clinics. Recruitment period was March 2010 through March 2011.
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| ID | Title | Description |
|---|---|---|
| FG000 | ACT-385781A (Epoprostenol for Injection) | The prepared solution was administered by continuous intravenous (i.v.) infusion via a central venous catheter using an ambulatory infusion pump. Administration was to be initiated at an infusion rate of 2 ng/kg/min, with up titration according to therapeutic need and tolerability. |
| FG001 | Flolan® (Epoprostenol Sodium) for Injection | The prepared solution was administered by continuous i.v. infusion via a central venous catheter using an ambulatory infusion pump. Administration was to be initiated at an infusion rate of 2 ng/kg/min, with up titration according to therapeutic need and tolerability |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | ACT-385781A (Epoprostenol for Injection) | The prepared solution was administered by continuous intravenous (i.v.) infusion via a central venous catheter using an ambulatory infusion pump. Administration was to be initiated at an infusion rate of 2 ng/kg/min, with up titration according to therapeutic need and tolerability. |
| BG001 |
| 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 | Dose Normalized Pharmacokinetics of 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha at 2 ng/kg/Min | The plasma concentration for the epoprostenol metabolite 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha was measured at 2 ng/kg/min just prior to the next up-titration. Dose-normalized concentrations are used to summarize the results. | A per-protocol analysis set that included all patients in the treated set who did not violate the protocol in a way that might affect the evaluation of the effect of the study drug(s) on the pharmacokinetic endpoints. | Posted | Median | Full Range | (pg/ml)/(ng/kg/min) | Day 1 |
|
Screening to day 28 for treatment-emergent (TE) adverse events (AEs) during dosing inpatient hospitalization and during outpatient period up to day 28 (EOT). TE serious AEs (SAEs) up to 30 days post study drug.
The assessment of safety was based on the collection of AEs, including SAEs and AEs that resulted in discontinuation of study treatment. All AEs that occurred up to the end of the last day of study treatment were recorded in the CRF and included in the clinical database. SAEs and deaths that occurred up to 30 days after the end of study treatment.
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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 | ACT-385781A (Epoprostenol for Injection) | The prepared solution was administered by continuous intravenous (i.v.) infusion via a central venous catheter using an ambulatory infusion pump. Administration was to be initiated at an infusion rate of 2 ng/kg/min, with up titration according to therapeutic need and tolerability. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ascites | Hepatobiliary disorders | MedDRA (14.0) | Systematic Assessment | 34 year female, Flolan, resolved without sequelae / unrelated to Flolan |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Distension | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
The EPITOME-1 study is an open label study without a primary endpoint. The sample size was determined based on feasibility and not a power calculation.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Wade Benton, PharmD, Director of Medical Affairs | Actelion Pharmaceuticals, US | 650-808-6562 | wade.benton@actelion.com |
| ID | Term |
|---|---|
| D000081029 | Pulmonary Arterial Hypertension |
| ID | Term |
|---|---|
| D006976 | Hypertension, Pulmonary |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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Not provided
| ID | Term |
|---|---|
| D011464 | Epoprostenol |
| ID | Term |
|---|---|
| D044062 | Prostaglandins I |
| D011453 | Prostaglandins |
| D015777 | Eicosanoids |
| D005231 | Fatty Acids, Unsaturated |
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| Flolan® |
| Drug |
Per Prescribing Information |
|
| Baseline and 28 days (+3 days) |
| Patients With New York Heart Association (NYHA) Functional Class Change (Improved or Worsened) From Baseline to Day 28 | Disease severity was assessed by NYHA classification of PAH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA. | From baseline to 28 days (+3 days) |
| Percentage Central Venous Blood Oxygen Saturation (ScVO2) - Baseline and Day 28 | Central venous blood oxygen saturation assessment was performed only in specific centers. Measurements for ScVO2 were performed during the inpatient hospitalization period on Day 1 (prior to drug initiation) and on Day 28 (EOT). Samples for ScVO2 were obtained by aspirating blood from the indwelling central venous catheter. After the sample had been drawn, the catheter was primed with study drug in order to refill the lumen to avoid interruption in treatment and sudden decompensation. | Baseline and 28 days |
| Blood Pressure - Baseline and Day 28 | Blood pressure (systolic and diastolic) were measured indirectly using an automatic oscillometric device, on the same arm for each measurement. The Blood Pressure was assessed at baseline and at Day 28 (End of Study Treatment visit). | Baseline and 28 days |
| Heart Rate - Baseline and Day 28 | Heart rate was measured indirectly using an automatic oscillometric device, on the same arm for each measurement. The Heart Rate was assessed at Baseline and at Day 28 (End of Study Treatment visit). | Baseline and 28 days |
| Body Weight - Baseline and Day 28 | Body weight was measured both at baseline and day 28. | Baseline and 28 days |
| Flolan® (Epoprostenol Sodium) for Injection |
The prepared solution was administered by continuous i.v. infusion via a central venous catheter using an ambulatory infusion pump. Administration was to be initiated at an infusion rate of 2 ng/kg/min, with up titration according to therapeutic need and tolerability |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| New York Heart Association (NYHA) Functional Class | Disease severity was assessed by NYHA classification of PH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA. | Number | participants |
|
| OG001 | Flolan® (Epoprostenol Sodium) for Injection | The prepared solution was administered by continuous i.v. infusion via a central venous catheter using an ambulatory infusion pump. Administration was to be initiated at an infusion rate of 2 ng/kg/min, with up titration according to therapeutic need and tolerability |
|
|
| Primary | Dose Normalized Pharmacokinetics of 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha at 4 ng/kg/Min | The plasma concentration for the epoprostenol metabolite 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha was measured at 4 ng/kg/min just prior to the next up-titration. Dose-normalized concentrations are used to summarize the results. | A per-protocol analysis set that included all patients in the treated set who did not violate the protocol in a way that might affect the evaluation of the effect of the study drug(s) on the pharmacokinetic endpoints. | Posted | Median | Full Range | (pg/ml)/(ng/kg/min) | Day 1 |
|
|
|
| Primary | Dose Normalized Pharmacokinetics of 6-keto-Prostacyclin F1alpha at 2 ng/kg/Min | The plasma concentration for the epoprostenol metabolite 6-keto-Prostacyclin F1alpha was measured at 2 ng/kg/min just prior to the next up-titration. Dose-normalized concentrations are used to summarize the results. | A per-protocol analysis set that included all patients in the treated set who did not violate the protocol in a way that might affect the evaluation of the effect of the study drug(s) on the pharmacokinetic endpoints. | Posted | Median | Full Range | (pg/ml)/(ng/kg/min) | Day 1 |
|
|
|
| Primary | Dose Normalized Pharmacokinetics of 6-keto-Prostacyclin F1alpha at 4 ng/kg/Min | The plasma concentration for the epoprostenol metabolite 6-keto-Prostacyclin F1alpha was measured at 4 ng/kg/min just prior to the next up-titration. Dose-normalized concentrations are used to summarize the results. | A per-protocol analysis set that included all patients in the treated set who did not violate the protocol in a way that might affect the evaluation of the effect of the study drug(s) on the pharmacokinetic endpoints. | Posted | Median | Full Range | (pg/ml)/(ng/kg/min) | Day 1 |
|
|
|
| Primary | Six-minute Walk Distance (6MWD) - Baseline and Day 28 | The 6-minute walk test (6MWT) was to be performed prior to initiating study treatment either during the screening visit or on Day 1 prior to drug initiation, and Day 28 (End of treatment (EOT)). This assessment is a non-encouraged test that measures the distance walked for a duration of 6 minutes. The 6MWD was recorded in the Case Report Form (CRF). | Patients who had both baseline and Day 28 assessments were included in the analysis. The analysis was conducted without replacement of missing values. | Posted | Median | Full Range | meters | Baseline and 28 days (+3 days) |
|
|
|
| Primary | Patients With New York Heart Association (NYHA) Functional Class Change (Improved or Worsened) From Baseline to Day 28 | Disease severity was assessed by NYHA classification of PAH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA. | Patients who had both baseline and Day 28 assessments were included in the analysis. The analysis was conducted without replacement of missing values. | Posted | Number | participants | From baseline to 28 days (+3 days) |
|
|
|
| Primary | Percentage Central Venous Blood Oxygen Saturation (ScVO2) - Baseline and Day 28 | Central venous blood oxygen saturation assessment was performed only in specific centers. Measurements for ScVO2 were performed during the inpatient hospitalization period on Day 1 (prior to drug initiation) and on Day 28 (EOT). Samples for ScVO2 were obtained by aspirating blood from the indwelling central venous catheter. After the sample had been drawn, the catheter was primed with study drug in order to refill the lumen to avoid interruption in treatment and sudden decompensation. | Patients who had both baseline and Day 28 assessments were included in the analysis. The analysis was conducted without replacement of missing values. | Posted | Median | Full Range | percentage oxygen saturation | Baseline and 28 days |
|
|
|
| Primary | Blood Pressure - Baseline and Day 28 | Blood pressure (systolic and diastolic) were measured indirectly using an automatic oscillometric device, on the same arm for each measurement. The Blood Pressure was assessed at baseline and at Day 28 (End of Study Treatment visit). | Patients who had both baseline and Day 28 assessments were included in the analysis. The analysis was conducted without replacement of missing values. | Posted | Median | Full Range | mm Hg | Baseline and 28 days |
|
|
|
| Primary | Heart Rate - Baseline and Day 28 | Heart rate was measured indirectly using an automatic oscillometric device, on the same arm for each measurement. The Heart Rate was assessed at Baseline and at Day 28 (End of Study Treatment visit). | Patients who had both baseline and Day 28 assessments were included in the analysis. The analysis was conducted without replacement of missing values. | Posted | Median | Full Range | Beats per minute | Baseline and 28 days |
|
|
|
| Primary | Body Weight - Baseline and Day 28 | Body weight was measured both at baseline and day 28. | Patients who had both baseline and Day 28 assessments were included in the analysis. The analysis was conducted without replacement of missing values. | Posted | Median | Full Range | kg | Baseline and 28 days |
|
|
|
| 6 |
| 20 |
| 20 |
| 20 |
| EG001 | Flolan® (Epoprostenol Sodium) for Injection | The prepared solution was administered by continuous i.v. infusion via a central venous catheter using an ambulatory infusion pump. Administration was to be initiated at an infusion rate of 2 ng/kg/min, with up titration according to therapeutic need and tolerability | 2 | 10 | 10 | 10 |
|
| Cardiac arrest | Cardiac disorders | MedDRA (14.0) | Systematic Assessment | 64 year male, Death (outcome), unrelated to ACT-385781 |
|
| Catheter Site Infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Cholestasis | Hepatobiliary disorders | MedDRA (14.0) | Systematic Assessment |
|
| Coagulopathy | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Device Related Sepsis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Fluid Overload | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (14.0) | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Pulmonary Hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Renal Failure Acute | Renal and urinary disorders | MedDRA (14.0) | Systematic Assessment |
|
| Right Ventricular Failure | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
|
| Supraventricular Tachycardia | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Ventricular Tachycardia | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Adverse Drug Reaction | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (14.0) | Systematic Assessment |
|
| Application Site Pruritus | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Application site Hypersensitivity | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Catheter Site Discharge | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Catheter Site Pruritus | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Catheter Site Rash | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Catheter Site Related Reaction | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Dermatitis Contact | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Feeling Jittery | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (14.0) | Systematic Assessment |
|
| Gastrooesophageal Reflux Disease | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Gout | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
|
| Haemoglobin Decreased | Investigations | MedDRA (14.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Hepatic Enzyme Increased | Investigations | MedDRA (14.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (14.0) | Systematic Assessment |
|
| Hyperventilation | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
|
| Implant Site Infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Incision Site Pain | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
|
| Infusion Site Vesicles | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (14.0) | Systematic Assessment |
|
| International Normalised Ratio Increased | Investigations | MedDRA (14.0) | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Localised oedema | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Medical Device Complication | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Metabolic Acidosis | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
|
| Muscle Spasms | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Muscloskeletal Chest Pain | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Neck Pain | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Oedema Peripheral | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Pain in Extremity | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Pain in Jaw | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Rales | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Rash Erythematous | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Renal Failure Acute | Renal and urinary disorders | MedDRA (14.0) | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Skin Ulcer | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Tooth Abscess | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Tropinin Increased | Investigations | MedDRA (14.0) | Systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Vulvovaginal Candidiasis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (14.0) | Systematic Assessment |
|
Not provided
Not provided
| D005227 |
| Fatty Acids |
| D008055 | Lipids |
| D012898 | Autacoids |
| D018836 | Inflammation Mediators |
| D001685 | Biological Factors |
| Diastolic Blood Pressure (Baseline) |
|
| Diastolic Blood Pressure (Day 28)) |
|