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This is a Phase 1, multi-center, open-label, single-dose, 2 period, 2 sequence cross-over trial to investigate the relative bioavailability of 2 solid oral pimasertib formulations in cancer subjects (Part A), followed by open-label pimasertib administration (Part B and trial extension phase).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pimasertib Capsule/Pimasertib Tablet | Experimental |
| |
| Pimasertib Tablet/Pimasertib Capsule | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pimasertib Capsule (Part A) | Drug | Pimasertib capsule administration at a single dose of 60 milligram (mg) orally on Day 1 in Part A. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | Maximum observed plasma concentration (Cmax) was calculated for Part A Pimasertib 60 mg Capsule and tablet. | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
| Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUC 0-t) | Area under the plasma concentration-time curve from time zero to the last sampling time (AUC0-t) at which the concentration was at or above the lower limit of quantification. | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC0-inf) | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 | |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Please Contact U.S. Medical Information Located in | Rockland | Massachusetts | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28289865 | Result | Mahadevan D, Mita M, Richards D, McClay E, Heist RS, Kumar A, Sundararajan S, Naing A. Phase I single dose, two-period and two-sequence cross-over trial to evaluate the relative bioavailability of two oral pimasertib formulations in advanced cancer patients. Cancer Chemother Pharmacol. 2017 Apr;79(4):681-688. doi: 10.1007/s00280-017-3258-0. Epub 2017 Mar 13. |
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A total of 45 subjects were screened. 38 subjects were enrolled and received the trial medication completed two sequence cross-over Part A and further continued in open label Part B.
First/last subject (informed consent): Nov 2013/Feb 2015. Clinical data cut-off: May 2014, Study completion date: Feb 2015
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A: Pimasertib Capsule Then Pimasertib Tablet | A single dose of 2 Pimasertib 30 mg capsule administered orally on Day 1 in first intervention period followed by a single dose of 3 Pimasertib 20 mg tablet single dose administered orally on Day 3, of Part A of the study. A washout period of 48 hours was maintained between the administration of the two treatments. |
| FG001 | Part A: Pimasertib Tablet Then Pimasertib Capsule | A single dose of 3 Pimasertib 20 mg tablet administered orally on Day 1 in first intervention period followed by a single dose of 2 Pimasertib 30 mg capsule single dose administered orally on Day 3, of Part A of the study. A washout period of 48 hours was maintained between the administration of the two treatments. |
| FG002 | Part B:Pimasertib Capsule | Pimasertib 2 capsule 30 mg orally twice daily up to 4 cycles of 21 days each in Part B and trial extension phase until disease progression, intolerable toxicity, subject withdrawal, loss to follow-up or death. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A |
| |||||||||||||
| Part B |
|
Safety analysis set included all subjects who received at least one dose of investigational medicinal product (IMP).
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| ID | Title | Description |
|---|---|---|
| BG000 | Entire Study Population | It included all the subjects randomized to receive either Pimasertib 60 mg capsule and Pimasertib 60 mg tablet first in Part A and Pimasertib 60 mg capsule in Part B of the study. |
| 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 | Maximum Observed Plasma Concentration (Cmax) | Maximum observed plasma concentration (Cmax) was calculated for Part A Pimasertib 60 mg Capsule and tablet. | Pharmacokinetic (PK) analysis set included all subjects who received the Part A IMP, had compliance with IMP intake in Part A, at least one post-treatment PK sample from each treatment period and absence of protocol deviations affecting bioavailability. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
|
Baseline up to end of trial (before the start of a new anticancer therapy or 30 ± 2 days after the last investigational medicinal product administration.)
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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 A: Pimasertib 60 mg Capsule | A single dose of 2 Pimasertib 30 mg capsule administered orally in one of the intervention periods in part A of the study. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac failure congestive | Cardiac disorders | MedDRA 18.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Merck KGaA Communication Center | Merck KGaA | +49-6151-72-5200 | service@merckgroup.com |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C550600 | N-(2,3-dihydroxypropyl)-1-((2-fluoro-4-iodophenyl)amino)isonicotinamide |
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|
| Pimasertib Tablet (Part A) | Drug | Pimasertib tablet administration at a single dose of 60 mg orally on Day 3 in Part A. |
|
|
| Pimasertib Tablet (Part A) | Drug | Pimasertib tablet administration at a single dose of 60 mg orally on Day 1 in Part A. |
|
|
| Pimasertib Capsule (Part A) | Drug | Pimasertib capsule administration at a single dose of 60 mg orally on Day 3 in Part A. |
|
|
| Pimasertib Capsule (Part B and trial extension phase) | Drug | Subjects completing Part A to receive pimasertib capsule at a dose of 60 mg orally twice daily in cycles of 21 days each in Part B and trial extension phase until disease progression, intolerable toxicity, subject withdrawal, loss to follow-up or death. |
|
|
| Apparent Terminal Half-life (t1/2) | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
| Apparent Total Body Clearance (CL/f) | Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
| Apparent Volume of Distribution (Vz/f) | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
| Terminal Rate Constant (λz) | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
| Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation | An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug administration until 30 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pre treatment state. | From the first dose of study drug administration until 30 days after the last dose of study drug administration, assessed up to 14 Months |
| Part B: Number of Subjects Who Experienced Complete Response (CR) | CR as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 defined as disappearance of all target lesions except lymph nodes (LN); LN must have a decrease in the short axis to less than (<)10 millimeter (mm). | Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months |
| Part B: Number of Subjects Who Experienced Partial Response (PR) | PR as per RECIST v1.1 defined as 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters. | Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months |
| Part B: Number of Subjects Who Experienced Stable Disease (SD) | SD as per RECIST v1.1 defined as neither shrinkage to qualify for PR nor increase to qualify for progressive disease (PD) taking the smallest sum diameters on study as reference. PR = 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters; PD = 20% increase in sum of diameters of target lesions; the appearance of >=1 new lesions. | Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months |
| Part B: Number of Subjects Who Experienced Progressive Disease (PD) | PD as per RECIST v1.1 defined as 20% increase in sum of diameters of target lesions; the appearance of >=1 new lesions. | Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months |
| NOT COMPLETED |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Part A: Pimasertib 60 mg Tablet |
A single dose of 3 Pimasertib 20 mg tablet administered orally in one of the intervention periods in part A of the study. |
|
|
| Secondary | Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC0-inf) | PK analysis set included all subjects who received the Part A IMP, had compliance with IMP intake in Part A, at least one post-treatment PK sample from each treatment period and absence of protocol deviations affecting bioavailability. Here N (number of participants analysed) signifies the number of subjects analysed for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
|
|
|
| Secondary | Time to Reach Maximum Observed Plasma Concentration (Tmax) | PK analysis set included all subjects who received the Part A IMP, had compliance with IMP intake in Part A, at least one post-treatment PK sample from each treatment period and absence of protocol deviations affecting bioavailability. | Posted | Median | Full Range | hour | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
|
|
|
| Secondary | Apparent Terminal Half-life (t1/2) | PK analysis set included all subjects who received the Part A IMP, had compliance with IMP intake in Part A, at least one post-treatment PK sample from each treatment period and absence of protocol deviations affecting bioavailability. Here N (number of participants analyzed) signifies the number of subjects analysed for this outcome measure. | Posted | Median | Full Range | hour | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
|
|
|
| Secondary | Apparent Total Body Clearance (CL/f) | Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. | PK analysis set included all subjects who received the Part A IMP, had compliance with IMP intake in Part A, at least one post-treatment PK sample from each treatment period and absence of protocol deviations affecting bioavailability. Here N (number of participants analyzed) signifies the number of subjects analysed for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter per hour (L/h) | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
|
|
|
| Secondary | Apparent Volume of Distribution (Vz/f) | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | PK analysis set included all subjects who received the Part A IMP, had compliance with IMP intake in Part A, at least one post-treatment PK sample from each treatment period and absence of protocol deviations affecting bioavailability. Here N (number of participants analyzed) signifies the number of subjects analysed for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
|
|
|
| Secondary | Terminal Rate Constant (λz) | PK analysis set included all subjects who received the Part A IMP, had compliance with IMP intake in Part A, at least one post-treatment PK sample from each treatment period and absence of protocol deviations affecting bioavailability. Here N (number of participants analyzed) signifies the number of subjects analysed for this outcome measure. | Posted | Median | Full Range | 1/h | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
|
|
|
| Primary | Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUC 0-t) | Area under the plasma concentration-time curve from time zero to the last sampling time (AUC0-t) at which the concentration was at or above the lower limit of quantification. | PK analysis set included all subjects who received the Part A IMP, had compliance with IMP intake in Part A, at least one post-treatment PK sample from each treatment period and absence of protocol deviations affecting bioavailability. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram per milliliter (h*ng/mL) | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3 |
|
|
|
| Secondary | Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation | An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug administration until 30 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pre treatment state. | Safety analysis set included all subjects who received at least one dose of IMP. | Posted | Number | subjects | From the first dose of study drug administration until 30 days after the last dose of study drug administration, assessed up to 14 Months |
|
|
|
| Secondary | Part B: Number of Subjects Who Experienced Complete Response (CR) | CR as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 defined as disappearance of all target lesions except lymph nodes (LN); LN must have a decrease in the short axis to less than (<)10 millimeter (mm). | Safety analysis set included all subjects who received at least one dose of IMP. | Posted | Number | subjects | Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months |
|
|
|
| Secondary | Part B: Number of Subjects Who Experienced Partial Response (PR) | PR as per RECIST v1.1 defined as 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters. | Safety analysis set included all subjects who received at least one dose of IMP. | Posted | Number | subjects | Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months |
|
|
|
| Secondary | Part B: Number of Subjects Who Experienced Stable Disease (SD) | SD as per RECIST v1.1 defined as neither shrinkage to qualify for PR nor increase to qualify for progressive disease (PD) taking the smallest sum diameters on study as reference. PR = 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters; PD = 20% increase in sum of diameters of target lesions; the appearance of >=1 new lesions. | Safety analysis set included all subjects who received at least one dose of IMP. | Posted | Number | subjects | Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months |
|
|
|
| Secondary | Part B: Number of Subjects Who Experienced Progressive Disease (PD) | PD as per RECIST v1.1 defined as 20% increase in sum of diameters of target lesions; the appearance of >=1 new lesions. | Safety analysis set included all subjects who received at least one dose of IMP. | Posted | Number | subjects | Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months |
|
|
|
| 1 |
| 38 |
| 18 |
| 38 |
| EG001 | Part A: Pimasertib 60 mg Tablet | A single dose of 3 Pimasertib 20 mg tablet administered orally in one of the intervention periods in part A of the study. | 0 | 37 | 17 | 37 |
| EG002 | Part B: Pimasertib Capsule (BID) | Pimasertib 2 capsule 30 mg orally twice daily up to 4 cycles of 21 days each in Part B and trial extension phase until disease progression, intolerable toxicity, subject withdrawal, loss to follow-up or death. | 19 | 38 | 37 | 38 |
| Diarrhoea | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Disease progression | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Non-cardiac chest pain | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Bile duct obstruction | Hepatobiliary disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Pneumonia klebsiella | Infections and infestations | MedDRA 18.0 | Non-systematic Assessment |
|
| Septic shock | Infections and infestations | MedDRA 18.0 | Non-systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 18.0 | Non-systematic Assessment |
|
| Pyelonephritis | Infections and infestations | MedDRA 18.0 | Non-systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA 18.0 | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Malignant ascites | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Non-systematic Assessment |
|
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Non-systematic Assessment |
|
| Seizure | Nervous system disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Retinal detachment | Eye disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Visual impairment | Eye disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Chorioretinopathy | Eye disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Macular detachment | Eye disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Colour blindness acquired | Eye disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Periorbital oedema | Eye disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Retinal exudates | Eye disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Chills | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Early satiety | General disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 18.0 | Non-systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA 18.0 | Non-systematic Assessment |
|
| Rash pustular | Infections and infestations | MedDRA 18.0 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 18.0 | Non-systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA 18.0 | Non-systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 18.0 | Non-systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA 18.0 | Non-systematic Assessment |
|
| Transaminases increased | Investigations | MedDRA 18.0 | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Hypovolaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Mental status changes | Psychiatric disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Swelling face | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 18.0 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 18.0 | Non-systematic Assessment |
|
Not provided
| Title | Measurements |
|---|---|
|
| TEAEs leading to discontinuation |
|