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This study is a prospective, randomized, double-blind, study of H01 (Hymecromone) in adults with pulmonary hypertension (PH). The primary objective of this study is to evaluate the safety and tolerability of oral H01 and the potential benefit of oral H01 on clinical measures of PH disease severity over 24 weeks.
Study Hypothesis:
Oral H01, at doses of 1600 mg per day, will be a safe and well-tolerated agent in adults with pulmonary hypertension over 24 weeks
The study's objectives are to evaluate:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental Treatment Oral Hymecromone (H01) | Experimental | Treatment will be initiated. Participants will be administered 800 mg of oral H01 two times a day (total dose: 1600 mg/day). Participants will continue to be on treatment for 24 weeks and will be monitored with assessments. |
|
| Placebo | Placebo Comparator | Participants randomized to placebo will receive oral tablet placebo (inactive ingredients) two times a day. Participants will continue to be on placebo for 24 weeks and will be monitored with assessments. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hymecromone (H01) | Drug | 800 mg oral H01 two times a day (total dose: 1600 mg/day). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Calculated Pulmonary Vascular Resistance (PVR) | Calculated pulmonary vascular resistance (PVR) measured by right heart catheterization (RHC). A normal PVR ranges between 0.25 and 1.6 wood units (WU). Pre-capillary pulmonary hypertension is characterized by a PVR greater than 3 WU. Greater PVR is indicative of increased disease severity. Either Fick or Thermodilution method can be utilized to measure cardiac output (CO) and calculate PVR. Fick method utilizes estimated oxygen consumption to measure CO and calculate PVR, while the thermodilution method utilizes temperature change to measure CO and calculate PVR. All measurements to calculate PVR were obtained at end-expiration (measuring the pressures at functional residual capacity of the lungs). | Baseline to end of treatment (Week 24; +/- 7 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events by Severity Using the NIH Common Terminology Criteria for Adverse Events (CTCAE) as a Measure of Safety and Tolerability of H01 in Adults With Pulmonary Hypertension |
|
| Measure | Description | Time Frame |
|---|---|---|
| Inflammatory Markers and PH-specific Biomarkers (ESR, HSCRP) | Change in inflammatory markers and PH-specific biomarkers (ESR, HSCRP) | Baseline to end of treatment (Week 24) |
| Pro-inflammatory Cytokines |
Inclusion Criteria:
Classified as WHO functional class II/III/IV despite treatment with maximally tolerated doses of 2 or more treatment modalities (exp. PDE5 inhibitors, guanylate cyclase stimulators, endothelin receptor antagonists, and prostanoids)
Baseline 6MWT: greater than 100 meters and less than 550 meters
Established diagnosis of Group 3 pulmonary hypertension as a result of interstitial lung disease OR established diagnosis of Group 1 pulmonary hypertension as a result of connective tissue disease, idiopathic, hereditary, drugs, or toxins.
Right heart catheterization at randomization showing pre-capillary pulmonary hypertension (mPAP ≥ 25 mmHg and PVR > 400 dynes * sec * cm^ -5) and:
Participants on chronic medication for PAH, PH, or underlying lung disease must be on a stable and optimized dose for at least 90 days prior to the first dose of the study drug.
Female participants who are heterosexually active must use an acceptable method of contraception: condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, IUD, or Hormone-based contraceptive
Be able to provide written informed consent and comply with study requirements
Be able to read, speak and understand English
Exclusion Criteria:
Participants with a diagnosis of PAH or PH for reasons due to any of the following:
Group 2, 4, or 5
Group 1 due to HIV, veno-occlusive disease, porto-pulmonary hypertension, congenital heart disease
Group 3 due to severe chronic obstructive pulmonary disease (COPD) or obstructive sleep apnea (OSA)
Total Lung Capacity (TLC) less than 60% predicted
FEV1/FVC less than 50% predicted or FEV1 less than 55% predicted
Inability to safely attempt completion of the 6MWD test
Use of experimental PAH treatments within the past 3 months
Current systemic treatment with hymecromone
Left sided heart disease as defined by either a PCWP greater than 20 mmHg and/or left ventricular ejection fraction less than 40%
Participants must not have 3 or more of the following left ventricular disease / dysfunction risk factors:
Historical evidence of significant coronary disease established by any of the following:
Significant valvular heart disease as determined by more than moderate findings on echocardiogram or history of valve replacement
Pregnant or actively breastfeeding
Female participants with childbearing potential not willing to use a form of birth control (including abstinence) during the study
Inability to undergo right heart catheterization
Acute pulmonary embolism within 90 days of randomization
Exacerbation of underlying lung disease or active pulmonary or upper respiratory infection within 30 days of randomizations
Use of any inhaled tobacco products or significant history of drug abuse within 3 months prior to randomization
Subject is receiving greater than 10L/min of oxygen supplementation by any mode of delivery at rest at baseline
Body mass index greater than 40kg/m2
Participants with history of dysphagia, achalasia, or difficulty swallowing capsules, tablets or pills
Participants with liver failure or AST or ALT greater than 2 times the upper limit of normal
Participants with total bilirubin levels greater than 2 times the upper limit of normal
Participants with CrCl less than 45
Use of any investigational drug/device, or participation in any investigational study with therapeutic intent within 30 days prior to randomization
Known allergy to hymecromone or any component thereof
Known allergy to any component of placebo (including wheat allergy, celiac disease, rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption)
Physician concern that participant may not adhere to the study protocol
Significant psychiatric, addictive, or other disorder that compromises the subject's ability to provide informed consent
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University School of Medicine | Stanford | California | 94305 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40451287 | Derived | Czepiel K, Nagy N, Panjalingam T, Kalinowski A, Frymoyer AR, Karmouty-Quintana H, Gu B, Hedlin H, Kaber G, Dobrota Lai S, Rosser JI, Bollyky PL, de Jesus Perez V, Zamanian RT. Randomised, placebo-controlled trial of oral hymecromone in adults with pulmonary hypertension. Thorax. 2025 Aug 15;80(9):632-640. doi: 10.1136/thorax-2024-222725. | |
| 37055910 |
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17 participants signed the informed consent. Out of these 17 participants,16 were randomized and started the study. The planned open-label extension study did not occur.
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| ID | Title | Description |
|---|---|---|
| FG000 | Experimental Treatment Oral Hymecromone (H01) | Participants receive H01 800 mg oral H01 two times a day (total dose: 1600 mg/day). |
| FG001 | Placebo | Participants receive oral tablet placebo (inactive ingredients) two times a day. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Experimental Treatment Oral Hymecromone (H01) | Participants receive H01 800 mg oral H01 two times a day (total dose: 1600 mg/day). |
| BG001 | Placebo | Participants receive oral tablet placebo (inactive ingredients) two times a day. |
| 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 | Calculated Pulmonary Vascular Resistance (PVR) | Calculated pulmonary vascular resistance (PVR) measured by right heart catheterization (RHC). A normal PVR ranges between 0.25 and 1.6 wood units (WU). Pre-capillary pulmonary hypertension is characterized by a PVR greater than 3 WU. Greater PVR is indicative of increased disease severity. Either Fick or Thermodilution method can be utilized to measure cardiac output (CO) and calculate PVR. Fick method utilizes estimated oxygen consumption to measure CO and calculate PVR, while the thermodilution method utilizes temperature change to measure CO and calculate PVR. All measurements to calculate PVR were obtained at end-expiration (measuring the pressures at functional residual capacity of the lungs). | Participants with data at the respective time point | Posted | Mean | Standard Deviation | Wood units (WU) | Baseline to end of treatment (Week 24; +/- 7 days) |
|
24 weeks
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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 | Experimental Treatment Oral Hymecromone (H01) | Participants receive H01 800 mg oral H01 two times a day (total dose: 1600 mg/day). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment | Not Related |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Roham Zamanian, MD | Stanford University School of Medicine | 650-725-5495 | zamanian@stanford.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 30, 2022 | Aug 15, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D006976 | Hypertension, Pulmonary |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006973 | Hypertension |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D006923 | Hymecromone |
| ID | Term |
|---|---|
| D014468 | Umbelliferones |
| D003374 | Coumarins |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 |
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| Placebo | Drug | Oral tablet placebo (inactive ingredients) two times a day. |
|
| Baseline to end of treatment (Week 24; +/- 7 days) |
| Mean Pulmonary Arterial Pressure (mPAP) | Mean pulmonary arterial pressure (mPAP) measured by RHC. A normal mPAP ranges between 9 and 19 mmHg at rest. Pre-capillary pulmonary hypertension is characterized by a mPAP greater than 20 mmHg at rest. Greater mPAP is indicative of increased disease severity. All measurements were obtained at end-expiration. | Baseline and end of treatment (Week 24; +/- 7 days) |
| 6 Minute Walk Distance Test (6 MWDT) | The 6MWDT (distance walked in 6 minutes) is used to determine functional exercise capacity, assess treatment efficacy, predict prognosis, and establish rehabilitation programs in PAH/PH patients. | Screening (up to 30 days prior to baseline) and weeks 4 (+/- 3 days), 12 (+/- 3 days), and 24 (+/- 7 days). |
| EMPHASIS-10 Scale Score | Quality of life (QOL) assessed using the EMPHASIS-10 questionnaire. The minimum score for this questionnaire is 0. The maximum score for this questionnaire is 50. Higher scores are indicative of poorer health-related quality of life (HRQoL) due to pulmonary hypertension. | Baseline and weeks 4 (+/- 3 days), 12 (+/- 3 days), and 24 (+/- 7 days) |
| St George Respiratory Questionnaire (SGRQ) Scale Score | Quality of life (QOL) assessed using the St George Respiratory Questionnaire (SGRQ). There are a total of 3 components in the questionnaire, including symptoms, activity, and impacts. Each component has a minimum weight of 0, and a maximum weight of 662.5, 1209.1, and 2117.8, respectively. The minimum weight of the total score (combining all 3 components) is 0, and the maximum weight of total score is 3989.4. The total score is calculated by dividing the summed weights from positive items in the questionnaire by the sum of weights for all items in the questionnaire and multiplying this by 100. The minimum total score is 0, the maximum is 100. Lower scores indicate better health status. | Baseline and weeks 4 (+/- 3 days), 12 (+/- 3 days), and 24 (+/- 7 days) |
| Serum Hyaluronan (HA) Concentration | Two samples were collected at each time point and mean values were calculated. The average of the two mean values is reported. The normal adult circulating level of hyaluronan ranges between 10 and 100 ng/mL. | Baseline and end of treatment (Week 24; +/- 7 days) |
| N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) | N-terminal pro-brain-type natriuretic peptide (NT-proBNP) is laboratory test used for assessing disease severity in pulmonary hypertension. The normal ranges for NT-proBNP are as follows: Male (Reflects 95th percentile w/o CHF ): 18-<44 yr: 36-93 pg/mL 44-<54 yr: 36-138 pg/mL 54-<64 yr: 36-177 pg/mL 64-<74 yr: 36-229 pg/mL 74 yr: 36-852 pg/mL Females (Reflects 95th percentile w/o CHF ): 18-<44 yr: 36-178 pg/mL 44-<54 yr: 36-192 pg/mL 54-<64 yr: 36-226 pg/mL 64-<74 yr: 36-353 pg/mL >74 yr: 36-624 pg/mL | Baseline and weeks 4 (+/- 3 days), 12 (+/- 3 days), and 24 (+/- 7 days) |
Change in pro-inflammatory cytokines
| Baseline to end of treatment (Week 24) |
| Forced Expiratory Volume in One Second (FEV1) | Change in Forced Expiratory Volume in one second (FEV1) | Baseline to end of treatment (Week 24) |
| Forced Vital Capacity (FVC) From Pulmonary Function Test (PFT) | Change in Forced Vital Capacity (FVC) from pulmonary function test (PFT) | Baseline to end of treatment (Week 24) |
| Total Lung Capacity (TLC) From Pulmonary Function Test (PFT) | Change in Total Lung Capacity (TLC) from pulmonary function test (PFT) | Baseline to end of treatment (Week 24) |
| Lung Diffusion Capacity (DLCO) From Pulmonary Function Test (PFT) | Change in Lung diffusion capacity (DLCO) from pulmonary function test (PFT) | Baseline to end of treatment (Week 24) |
| Exhaled Breath Condensate (EBC) Hyaluronan Concentrations | Change in exhaled breath condensate (EBC) hyaluronan concentrations | Baseline to end of treatment (Week 24) |
| Pharmacokinetics (H01 and Metabolite Serum Concentrations) | Describe the pharmacokinetics (H01 and metabolite serum concentrations) | Baseline to end of treatment (Week 24) |
| HA Fragment Size | Describe HA fragment size | Baseline to end of treatment (Week 24) |
| Salman L, Martinez L, Faddoul G, Manning C, Ali K, Salman M, Vazquez-Padron R. Hyaluronan Inhibition as a Therapeutic Target for Diabetic Kidney Disease: What Is Next? Kidney360. 2023 Jun 1;4(6):e851-e860. doi: 10.34067/KID.0000000000000126. Epub 2023 Apr 14. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
Participants receive H01 800 mg oral H01 two times a day (total dose: 1600 mg/day). |
| OG001 | Placebo | Participants receive oral tablet placebo (inactive ingredients) two times a day. |
|
|
|
| Secondary | Number of Participants With Adverse Events by Severity Using the NIH Common Terminology Criteria for Adverse Events (CTCAE) as a Measure of Safety and Tolerability of H01 in Adults With Pulmonary Hypertension |
| Posted | Count of Participants | Participants | Baseline to end of treatment (Week 24; +/- 7 days) |
|
|
|
| Secondary | Mean Pulmonary Arterial Pressure (mPAP) | Mean pulmonary arterial pressure (mPAP) measured by RHC. A normal mPAP ranges between 9 and 19 mmHg at rest. Pre-capillary pulmonary hypertension is characterized by a mPAP greater than 20 mmHg at rest. Greater mPAP is indicative of increased disease severity. All measurements were obtained at end-expiration. | Participants with data at the respective time point. | Posted | Mean | Standard Deviation | mmHg | Baseline and end of treatment (Week 24; +/- 7 days) |
|
|
|
|
| Secondary | 6 Minute Walk Distance Test (6 MWDT) | The 6MWDT (distance walked in 6 minutes) is used to determine functional exercise capacity, assess treatment efficacy, predict prognosis, and establish rehabilitation programs in PAH/PH patients. | Participants with data at the respective time point. | Posted | Mean | Standard Deviation | meters | Screening (up to 30 days prior to baseline) and weeks 4 (+/- 3 days), 12 (+/- 3 days), and 24 (+/- 7 days). |
|
|
|
|
| Secondary | EMPHASIS-10 Scale Score | Quality of life (QOL) assessed using the EMPHASIS-10 questionnaire. The minimum score for this questionnaire is 0. The maximum score for this questionnaire is 50. Higher scores are indicative of poorer health-related quality of life (HRQoL) due to pulmonary hypertension. | Participants with data at the respective timepoint. | Posted | Mean | Standard Deviation | score on a scale | Baseline and weeks 4 (+/- 3 days), 12 (+/- 3 days), and 24 (+/- 7 days) |
|
|
|
|
| Secondary | St George Respiratory Questionnaire (SGRQ) Scale Score | Quality of life (QOL) assessed using the St George Respiratory Questionnaire (SGRQ). There are a total of 3 components in the questionnaire, including symptoms, activity, and impacts. Each component has a minimum weight of 0, and a maximum weight of 662.5, 1209.1, and 2117.8, respectively. The minimum weight of the total score (combining all 3 components) is 0, and the maximum weight of total score is 3989.4. The total score is calculated by dividing the summed weights from positive items in the questionnaire by the sum of weights for all items in the questionnaire and multiplying this by 100. The minimum total score is 0, the maximum is 100. Lower scores indicate better health status. | Participants with data at the respective timepoint. | Posted | Mean | Standard Deviation | score on a scale | Baseline and weeks 4 (+/- 3 days), 12 (+/- 3 days), and 24 (+/- 7 days) |
|
|
|
|
| Secondary | Serum Hyaluronan (HA) Concentration | Two samples were collected at each time point and mean values were calculated. The average of the two mean values is reported. The normal adult circulating level of hyaluronan ranges between 10 and 100 ng/mL. | Posted | Mean | Standard Deviation | ng/mL | Baseline and end of treatment (Week 24; +/- 7 days) |
|
|
|
|
| Secondary | N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) | N-terminal pro-brain-type natriuretic peptide (NT-proBNP) is laboratory test used for assessing disease severity in pulmonary hypertension. The normal ranges for NT-proBNP are as follows: Male (Reflects 95th percentile w/o CHF ): 18-<44 yr: 36-93 pg/mL 44-<54 yr: 36-138 pg/mL 54-<64 yr: 36-177 pg/mL 64-<74 yr: 36-229 pg/mL 74 yr: 36-852 pg/mL Females (Reflects 95th percentile w/o CHF ): 18-<44 yr: 36-178 pg/mL 44-<54 yr: 36-192 pg/mL 54-<64 yr: 36-226 pg/mL 64-<74 yr: 36-353 pg/mL >74 yr: 36-624 pg/mL | Posted | Mean | Standard Deviation | pg/ml | Baseline and weeks 4 (+/- 3 days), 12 (+/- 3 days), and 24 (+/- 7 days) |
|
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|
| Other Pre-specified | Inflammatory Markers and PH-specific Biomarkers (ESR, HSCRP) | Change in inflammatory markers and PH-specific biomarkers (ESR, HSCRP) | Not Posted | Baseline to end of treatment (Week 24) | Participants |
| Other Pre-specified | Pro-inflammatory Cytokines | Change in pro-inflammatory cytokines | Not Posted | Baseline to end of treatment (Week 24) | Participants |
| Other Pre-specified | Forced Expiratory Volume in One Second (FEV1) | Change in Forced Expiratory Volume in one second (FEV1) | Not Posted | Baseline to end of treatment (Week 24) | Participants |
| Other Pre-specified | Forced Vital Capacity (FVC) From Pulmonary Function Test (PFT) | Change in Forced Vital Capacity (FVC) from pulmonary function test (PFT) | Not Posted | Baseline to end of treatment (Week 24) | Participants |
| Other Pre-specified | Total Lung Capacity (TLC) From Pulmonary Function Test (PFT) | Change in Total Lung Capacity (TLC) from pulmonary function test (PFT) | Not Posted | Baseline to end of treatment (Week 24) | Participants |
| Other Pre-specified | Lung Diffusion Capacity (DLCO) From Pulmonary Function Test (PFT) | Change in Lung diffusion capacity (DLCO) from pulmonary function test (PFT) | Not Posted | Baseline to end of treatment (Week 24) | Participants |
| Other Pre-specified | Exhaled Breath Condensate (EBC) Hyaluronan Concentrations | Change in exhaled breath condensate (EBC) hyaluronan concentrations | Not Posted | Baseline to end of treatment (Week 24) | Participants |
| Other Pre-specified | Pharmacokinetics (H01 and Metabolite Serum Concentrations) | Describe the pharmacokinetics (H01 and metabolite serum concentrations) | Not Posted | Baseline to end of treatment (Week 24) | Participants |
| Other Pre-specified | HA Fragment Size | Describe HA fragment size | Not Posted | Baseline to end of treatment (Week 24) | Participants |
| 0 |
| 10 |
| 1 |
| 10 |
| 3 |
| 10 |
| EG001 | Placebo | Participants receive oral tablet placebo (inactive ingredients) two times a day. | 0 | 6 | 3 | 6 | 3 | 6 |
|
| Thromboembolic event | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment | Not Related |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment | Not Related |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment | Not Related |
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| Chest pain - cardiac | Cardiac disorders | CTCAE (4.0) | Systematic Assessment | Not Related |
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| Lung infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment | Not Related |
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| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment | Possibly Related |
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| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment | Not Related |
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| Creatinine increased | Investigations | CTCAE (4.0) | Systematic Assessment | Not Related |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment | Possibly Related |
|
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| D002318 |
| Cardiovascular Diseases |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| Grade 3 (severe) |
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| Grade 4 (life-threatening) |
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| Grade 5 (death) |
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