Study to Explore the Safety, Tolerability and Efficacy of MK-3475 in Combination With INCB024360 in Participants With Selected Cancers
Study Details
Study Description
Brief Summary
The purpose of this study was to assess the safety, tolerability, and efficacy when combining MK-3475 and INCB024360 in participants with certain cancers. This study was conducted in 2 phases, Phase 1 and Phase 2.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Phase 1: MK-3475 + INCB024360 Phase 1: MK-3475 + INCB024360 25 mg twice a day (BID) as starting dose, followed by dose escalations (Phase 1) until recommended phase 2 dose of INCB024360 is determined |
Drug: MK-3475
IV infusion
Drug: INCB024360
Oral daily dosing
|
Experimental: Phase 2: MK-3475 + INCB024360 (recommended phase 2 dose) |
Drug: MK-3475
IV infusion
Drug: INCB024360
Oral daily dosing
|
Outcome Measures
Primary Outcome Measures
- Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events [Approximately 54 months]
An adverse event is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after a participant provides informed consent. A TEAE is any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug. Serious adverse event (SAE) is defined as an event that meets 1 of the following criteria: is fatal or life threatening, results in persistent or significant disability or incapacity, constitutes a congenital anomaly or birth defect, is clinically meaningful (i.e. defined as an event that jeopardizes the participant or requires potential medical or surgical intervention to prevent 1 of the outcomes listed above) or requires inpatient hospitalization or prolongation of existing hospitalization.
- Phase 2: Objective Response Rate (ORR) [Approximately 54 months]
ORR was percentage of participants with best overall response [complete response (CR) or partial response (PR)], per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Secondary Outcome Measures
- Phase 2: Duration of Response (DOR) [Up to 54 months]
Duration of response is the time from the first overall response contributing to an objective response (complete or partial response) for DLBCL to the date of death or the date of first overall response of progressive diseasemeasured (by irRECIST for solid tumors or the Lugano Classification, whichever is earliest.
- Phase 2: Progression Free Survival (PFS) [Up to 54 months]
Progression-free survival is defined as number of days from the first day of taking study drug to the earlier of death or disease progression by irRECIST v1.1 for select solid tumors and modified Lugano Classification for DLBCL.
- Phase 2: Duration of Disease Control [Up to 54 months]
The duration of disease control is the time from the treatment start date to the first objective response of PD (by irRECIST v1.1 or Lugano Classification), death, or last tumor assessment date (if PD/death not present), for subjects with best overall response of SD or better.
- Phase 2: Overall Survival (OS) [Up to 54 months]
Overall survival is determined from the date of first dose until death due to any cause.
- Phase 2: Ordinal Categorical Response Score [Up to 54 months]
Ordinal categorical response score, determined by radiographic disease assessments per irRECIST v1.1. The 5-category ordinal response endpoint is determined at a given timepoint by classifying response into one of the following groups: 1 = Complete response per irRECIST v1.1 2 = Very good response, defined as > 60% tumor reduction 3 = Minor response, defined as > 30% to ≤ 60% tumor reduction 4 = Stable disease per irRECIST v1.1 5 = Progressive disease per irRECIST v1.1
- Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events [Up to 54 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Subjects with histologically or cytologically non-small cell lung cancer (NSCLC), melanoma, transitional cell carcinoma of the genitourinary (GU) tract, renal cell cancer, triple negative breast cancer, adenocarcinoma of the endometrium or squamous cell carcinoma of the head and neck (Phase 1).
-
Subjects with histologically confirmed melanoma, NSCLC, transitional cell carcinoma of the GU tract, TNBC, SCCHN, ovarian cancer, MSI high colorectal cancer (CRC), RCC, gastric cancer, HCC and DLBCL (Phase 2).
-
Life expectancy > 12 weeks.
-
Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1.
-
Presence of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or Lugano Classification for subjects with DLBCL.
-
Laboratory and medical history parameters within protocol-defined range.
-
For Phase 1: Subjects who have advanced or metastatic disease as noted above that have received at least one prior therapy or have advanced or metastatic disease for which no curative treatment is available may be enrolled.
-
For Phase 2 expansion cohorts: Subjects with NSCLC, melanoma (checkpoint inhibitor naïve, primary refractory melanoma, relapsed melanoma), transitional cell carcinoma of the GU tract, SCCHN, ovarian cancer, MSI high CRC, RCC, DLBCL, TNBC, gastric cancer, and HCC.
-
Phase 2 expansion: NSCLC
-
Subjects who have received at least 1 prior platinum-based therapy. Subjects who have a non-platinum-based regimen may be enrolled with medical monitor approval.
-
Tumors with epidermal growth factor receptor mutation positive or anaplastic lymphoma kinase fusion oncogene positive treated with a tyrosine kinase inhibitor are permitted; however, subjects should have progressed on or be intolerant to the targeted therapy.
-
Subjects must not have received immunotherapy with programmed death receptor-1 (PD-1) or cytotoxic T-lymphocyte antigen (CTLA-4) targeted therapy.
-
Phase 2 expansion: Melanoma
-
Documentation of V600E-activating BRAF mutation status.
-
Prior systemic therapy requirements.
-
Melanoma immune checkpoint-naïve: Subjects must not have received immunotherapy with anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy. Exception: Prior anti-CTLA-4 in the adjuvant setting would be permitted.
-
Primary refractory melanoma: Subjects must have received prior treatment with anti-PD-1 or anti-PD-L1 therapy (alone or as part of a combination) in the advanced or metastatic setting and have progressive disease as their best response to treatment that is confirmed 4 weeks later.
-
Relapsed melanoma: Subjects must have received prior anti-PD-1 or anti-PD-L1 therapy (alone or as part of a combination) in the advanced or metastatic setting and achieved partial response ore complete response but later have confirmed progressive disease.
-
Subjects enrolling in the primary refractory or relapsed melanoma must be willing to undergo mandatory pretreatment and on-treatment biopsies.
-
Ocular melanoma is excluded.
-
Phase 2 expansion: Transitional cell carcinoma of the GU tract
-
Metastatic or locally advanced and not amenable to curative therapy with disease progression on or after platinum-based chemotherapy or alternative therapy if platinum-based therapy is not appropriate.
-
Prior PD-1 or CTLA-4 targeted therapies are excluded
-
Phase 2 expansion: SCCHN
-
Histologically confirmed metastatic or recurrent squamous cell carcinoma not amenable to local therapy with curative intent (surgery or radiation with or without chemotherapy). Carcinoma of the nasopharynx, salivary gland, or * *Subjects must have received at least 1 prior systemic chemotherapy regimen that must have included a platinum-based therapy.
-
Prior PD-1 or CTLA-4 targeted therapies are excluded.
-
Phase 2 expansion: Ovarian cancer
-
Subjects with FIGO Stage Ic, Stage II, Stage III, Stage IV, recurrent, or persistent (unresectable) histologically confirmed epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube carcinoma.
-
Subjects must have received a platinum-taxane-based regimen as first-line therapy.
-
Prior PD-1 or CTLA-4 targeted therapies are excluded.
-
Borderline, low-malignant-potential epithelial carcinoma per histopathology is excluded.
-
Phase 2 expansion: Relapsed or refractory DLBCL
-
Prior allogeneic stem-cell transplantation is excluded.
-
Must have received > or = 1 prior treatment regimen.
-
Not a candidate for curative therapy or hematopoietic stem-cell transplantation (either due to disease burden, fitness, or preference).
-
Prior PD-1 or CTLA-4 targeted therapies are excluded.
-
Phase 2 expansion: TNBC
-
Histologically confirmed breast adenocarcinoma that is unresectable loco regional, or metastatic
-
Pathologically confirmed as triple negative, source documented, defined as both of the following:
-
Estrogen receptor (ER) and progesterone receptor (PgR) negative.
-
Human epidermal growth factor receptor 2 (HER2) negative as per American Society of Clinical Oncology/College of American Pathologists guidelines.
-
Subject must have received at least 1 prior systemic regimen for advanced or metastatic disease
-
Prior PD-1 or CTLA-4 targeted therapies are excluded.
-
Phase 2 expansion: RCC
-
Subjects with histological or cytological confirmation of clear cell RCC.
-
Not curable by surgery.
-
Subjects must have received prior antiangiogenic therapy.
-
Subjects must not have received prior immunotherapy with anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy.
-
Phase 2 expansion: MSI high CRC
-
Subjects with histological confirmation of locally advanced unresectable or metastatic MSI high CRC.
-
MSI status is, respectively, determined by examining CRC tumor.
-
Subjects may have received no more than 2 lines of prior therapy for advanced disease.
-
Phase 2 expansion: Gastric Cancer
-
Must have histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma.
-
Must have progression on or after therapy containing platinum/fluoropyrimidine or refused standard therapy.
-
Subjects may have received no more than 2 lines of prior therapy for advanced disease.
-
Prior PD-1 or CTLA-4 targeted therapies are excluded.
-
Phase 2 expansion: HCC
-
Must have histologically or cytologically confirmed diagnosis of HCC (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible).
-
Barcelona Clinic Liver Cancer (BCLC) Stage C disease (Llovet et al 1999), or BCLC Stage B disease.
-
Subjects may have received no more than 2 lines of prior therapy for the advanced disease
-
Must have progressed on, refused, or were intolerant of sorafenib.
-
The following are excluded: Subjects with liver transplants, clear invasion of the bile duct or main portal branch(es), or hepatorenal syndrome, or subjects who have required esophageal variceal ablation within 28 days of starting study treatment.
-
Prior PD-1 or CTLA-4 targeted therapies are excluded.
-
Tumor biopsies are required. If a subject has inaccessible lesions, such as in ovarian cancer, HCC, or gastric cancer, or highly vascular lesions, such as RCC, enrollment may be considered with medical monitor approval, and archived tissue may be acceptable.
-
Females of child-bearing potential and males who use adequate birth control through 120 days post dose.
Exclusion Criteria:
-
Subjects who participated in any other study in which receipt of an investigational study drug or device occurred within 2 weeks or 5 half-lives (whichever is longer) prior to first dose.
-
Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). Exception: Prior anti-CTLA-4 in the adjuvant setting for subjects with melanoma would be permitted.
-
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable.
-
Has an active autoimmune disease.
-
Has evidence of noninfectious pneumonitis that required steroids or current pneumonitis.
-
Live vaccine use within 30 days of first dose of study medication.
-
Monoamine oxidase inhibitors.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | UC San Diego Moores Cancer Center | La Jolla | California | United States | 92093 |
2 | The Angeles Clinic and Research Institute | Los Angeles | California | United States | 90025 |
3 | US Davis Cancer Center | Sacramento | California | United States | 95817 |
4 | University Of Colorado Cancer Center | Aurora | Colorado | United States | 80045 |
5 | University of Connecticut Health Center Carole And Ray Neag Comprehensive Cancer Center | Farmington | Connecticut | United States | 06030-1601 |
6 | Miami Cancer Institute at Baptist Health, Inc | Miami | Florida | United States | 33176 |
7 | Georgia Cancer Specialists affiliated with Northside Hospital Cancer Institute | Atlanta | Georgia | United States | 30342 |
8 | The University of Chicago Medicine | Chicago | Illinois | United States | 60637 |
9 | St. Francis Cancer Center | Topeka | Kansas | United States | 66618 |
10 | Greater Baltimore Cancer Center | Baltimore | Maryland | United States | 21204 |
11 | St. Agnes Hospital Cancer Institute | Baltimore | Maryland | United States | 21229 |
12 | The Center for Cancer and Blood Disorders (RCCA MD LLC- Maryland Division) | Bethesda | Maryland | United States | 20817 |
13 | University of Michigan Hospital and Health Systems | Ann Arbor | Michigan | United States | 48109 |
14 | Health Partners Institute | Saint Louis Park | Minnesota | United States | 55426 |
15 | Hackensack University Medical Center - John Theurer Cancer Center | Hackensack | New Jersey | United States | 07601 |
16 | The Christ Hospital Hematology Oncology, Lindner Research Center | Cincinnati | Ohio | United States | 45219 |
17 | University of Pennsylvania Hospital | Philadelphia | Pennsylvania | United States | 19104 |
18 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111-2497 |
19 | University of Pittsburgh Medical Center Hillman Cancer Center | Pittsburgh | Pennsylvania | United States | 15232 |
20 | Greenville Health System Cancer Institute | Greenville | South Carolina | United States | 29605 |
21 | West Cancer Center | Germantown | Tennessee | United States | 38120 |
22 | Sarah Cannon Research Institute at Tennessee Oncology | Nashville | Tennessee | United States | 37203-2173 |
23 | University Of Texas Southwestern Medical Center At Dallas | Dallas | Texas | United States | 75390 |
24 | Virginia Cancer Specialists | Arlington | Virginia | United States | 22031 |
Sponsors and Collaborators
- Incyte Corporation
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Mark Jones, MD, Incyte Corporation
Study Documents (Full-Text)
More Information
Publications
None provided.- INCB 24360-202/ ECHO-202
Study Results
Participant Flow
Recruitment Details | Participants took part in the study at 22 investigative sites in the United States from 17July 2014 to 06 November 2020. |
---|---|
Pre-assignment Detail | Prior to 17May18 study amended/discontinued, 444 participants were enrolled. Survival follow up and monotherapy option after discontinuation of combination were removed so anyone in survival follow up were discontinued the study and were assigned to "study terminated by sponsor" because completed was not an option in the database for those in survival follow up. 1 patient on combo treatment did not move to the monotherapy so they were also assigned to this reason for discontinuing. |
Arm/Group Title | Phase 1: Epacadostat 25 mg BID | Phase 1: Epacadostat 50 mg BID | Phase 1: Epacadostat 100 mg BID | Phase 1: Epacadostat 300 mg BID | Phase 2: Epacadostat 100 mg BID |
---|---|---|---|---|---|
Arm/Group Description | Epacadostat 25 mg tablet orally twice daily (BID) starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. | Epacadostat 50 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg or 200mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. | Epacadostat 100 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg or 200mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. | Epacadostat 300 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 200 mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. | Epacadostat 100 mg tablet orally BID in combination with pembrolizumab 200 mg intravenously every 3 weeks (Q3W). |
Period Title: Overall Study | |||||
STARTED | 4 | 20 | 18 | 20 | 382 |
COMPLETED | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 4 | 20 | 18 | 20 | 382 |
Baseline Characteristics
Arm/Group Title | Phase 1: Epacadostat 25 mg BID | Phase 1: Epacadostat 50 mg BID | Phase 1: Epacadostat 100 mg BID | Phase 1: Epacadostat 300 mg BID | Phase 2: Epacadostat 100 mg BID | Total |
---|---|---|---|---|---|---|
Arm/Group Description | Epacadostat 25 mg tablet orally twice daily (BID) starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. | Epacadostat 50 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg or 200mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. | Epacadostat 100 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg or 200mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. | Epacadostat 300 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 200 mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. | Epacadostat 100 mg tablet orally BID in combination with pembrolizumab 200 mg intravenously every 3 weeks (Q3W). | Total of all reporting groups |
Overall Participants | 4 | 20 | 18 | 20 | 382 | 444 |
Age (years) [Mean (Standard Deviation) ] | ||||||
Mean (Standard Deviation) [years] |
48.8
(18.01)
|
60.8
(12.97)
|
63.2
(13.67)
|
59.2
(13.06)
|
62.7
(11.60)
|
62.3
(11.92)
|
Sex: Female, Male (Count of Participants) | ||||||
Female |
3
75%
|
9
45%
|
6
33.3%
|
9
45%
|
181
47.4%
|
208
46.8%
|
Male |
1
25%
|
11
55%
|
12
66.7%
|
11
55%
|
201
52.6%
|
236
53.2%
|
Race/Ethnicity, Customized (Count of Participants) | ||||||
White/Caucasian |
1
25%
|
20
100%
|
18
100%
|
17
85%
|
337
88.2%
|
393
88.5%
|
Black/African-American |
1
25%
|
0
0%
|
0
0%
|
2
10%
|
19
5%
|
22
5%
|
Asian |
1
25%
|
0
0%
|
0
0%
|
1
5%
|
15
3.9%
|
17
3.8%
|
Native Hawaiian/Pacific Islander |
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.2%
|
Other |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
9
2.4%
|
9
2%
|
Missing |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
0.5%
|
2
0.5%
|
Race/Ethnicity, Customized (Count of Participants) | ||||||
Hispanic or Latino |
0
0%
|
0
0%
|
1
5.6%
|
1
5%
|
16
4.2%
|
18
4.1%
|
Not Hispanic or Latino |
4
100%
|
20
100%
|
17
94.4%
|
19
95%
|
353
92.4%
|
413
93%
|
Unknown |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
10
2.6%
|
10
2.3%
|
Other |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
0.5%
|
2
0.5%
|
Missing |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.3%
|
1
0.2%
|
Outcome Measures
Title | Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events |
---|---|
Description | An adverse event is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after a participant provides informed consent. A TEAE is any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug. Serious adverse event (SAE) is defined as an event that meets 1 of the following criteria: is fatal or life threatening, results in persistent or significant disability or incapacity, constitutes a congenital anomaly or birth defect, is clinically meaningful (i.e. defined as an event that jeopardizes the participant or requires potential medical or surgical intervention to prevent 1 of the outcomes listed above) or requires inpatient hospitalization or prolongation of existing hospitalization. |
Time Frame | Approximately 54 months |
Outcome Measure Data
Analysis Population Description |
---|
The safety evaluable population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab). |
Arm/Group Title | Phase 1: Epacadostat 25 mg BID | Phase 1: Epacadostat 50 mg BID | Phase 1: Epacadostat 100 mg BID | Phase 1: Epacadostat 300 mg BID |
---|---|---|---|---|
Arm/Group Description | Epacadostat 25 mg tablet orally twice daily (BID) starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. | Epacadostat 50 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg or 200mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. | Epacadostat 100 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg or 200mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. | Epacadostat 300 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 200 mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. |
Measure Participants | 4 | 20 | 18 | 20 |
SAE |
0
0%
|
40.0
200%
|
50.0
277.8%
|
45.0
225%
|
TEAS |
100.
2500%
|
95.0
475%
|
94.4
524.4%
|
100.
500%
|
Title | Phase 2: Objective Response Rate (ORR) |
---|---|
Description | ORR was percentage of participants with best overall response [complete response (CR) or partial response (PR)], per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Time Frame | Approximately 54 months |
Outcome Measure Data
Analysis Population Description |
---|
The efficacy evaluable population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab). Number analyzed indicated participants analyzed in the respective tumor type. |
Arm/Group Title | Epacadostat 100 mg BID+ Pembrolizumab 200 mg Q3W |
---|---|
Arm/Group Description | Epacadostat 100 mg tablet orally BID in combination with pembrolizumab 200 mg intravenously every 3 weeks (Q3W). |
Measure Participants | 382 |
Triple negative breast cancer |
11.1
277.5%
|
Microsatellite-instability high colorectal cancer |
43.8
1095%
|
Gastric cancer |
22.2
555%
|
Hepatocellular carcinoma |
16.7
417.5%
|
Melanoma - immune checkpoint-naïve |
60.5
1512.5%
|
Non-small cell lung cancer (NSCLC) (tumor proportion score (TPS) < 50% or indeterminate) |
30.8
770%
|
NSCLC programmed cell death ligand (PD-L1) low negative (TPS < 50%) |
24.4
610%
|
Ovarian cancer |
8.1
202.5%
|
Renal cell carcinoma |
32.4
810%
|
Squamous cell carcinoma of the head and neck |
33.3
832.5%
|
Transitional carcinoma of the genitourinary (GU) tract |
30.6
765%
|
Diffuse large B-cell lymphoma |
19.2
480%
|
Primary Refractory Melanoma |
0.0
0%
|
Relapsed Melanoma |
0.0
0%
|
Title | Phase 2: Duration of Response (DOR) |
---|---|
Description | Duration of response is the time from the first overall response contributing to an objective response (complete or partial response) for DLBCL to the date of death or the date of first overall response of progressive diseasemeasured (by irRECIST for solid tumors or the Lugano Classification, whichever is earliest. |
Time Frame | Up to 54 months |
Outcome Measure Data
Analysis Population Description |
---|
The efficacy evaluable population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab). Number analyzed indicated participants analyzed in the respective tumor type and those who responded. |
Arm/Group Title | Epacadostat 100 mg BID+ Pembrolizumab 200 mg Q3W |
---|---|
Arm/Group Description | Epacadostat 100 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 200 mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. |
Measure Participants | 105 |
Hepatocellular Carcinoma |
NA
|
Triple Negative Breast Cancer |
NA
|
Immune Checkpoint-naïve Melanoma |
NA
|
NSCLC high positive (PD-L1 TPS ≥ 50%) |
12.44
|
NSCLC low/negative or indeterminate (PD-L1 TPS < 50% or indeterminate) |
11.93
|
NSCLC (TPS 0%) |
NA
|
NSCLC Unknown |
10.84
|
Renal Cell Carcinoma |
16.95
|
Squamous Cell Carcinoma of the Head and Neck |
11.33
|
Transitional Cell Carcinoma of the GU Tract |
NA
|
Ovarian Cancer |
NA
|
Gastric Cancer |
NA
|
MSI high Colorectal Cancer |
NA
|
DLBCL |
3.66
|
Title | Phase 2: Progression Free Survival (PFS) |
---|---|
Description | Progression-free survival is defined as number of days from the first day of taking study drug to the earlier of death or disease progression by irRECIST v1.1 for select solid tumors and modified Lugano Classification for DLBCL. |
Time Frame | Up to 54 months |
Outcome Measure Data
Analysis Population Description |
---|
The efficacy evaluable population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab). Number analyzed indicated participants analyzed in the respective tumor type. |
Arm/Group Title | Epacadostat 100 mg BID+ Pembrolizumab 200 mg Q3W |
---|---|
Arm/Group Description | Epacadostat 100 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 200 mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. |
Measure Participants | 382 |
Hepatocellular Carcinoma |
5.49
|
Triple Negative Breast Cancer |
1.97
|
Immune Checkpoint-naïve Melanoma |
16.69
|
Primary Refractory Melanoma |
1.69
|
Relapsed Melanoma |
2.60
|
NSCLC |
4.09
|
Renal Cell Carcinoma |
4.50
|
Squamous Cell Carcinoma of the Head and Neck |
4.37
|
Transitional Cell Carcinoma of the GU Tract |
4.40
|
Ovarian Cancer |
2.10
|
Gastric Cancer |
1.97
|
MSI high Colorectal Cancer |
6.11
|
DLBCL |
2.63
|
Title | Phase 2: Duration of Disease Control |
---|---|
Description | The duration of disease control is the time from the treatment start date to the first objective response of PD (by irRECIST v1.1 or Lugano Classification), death, or last tumor assessment date (if PD/death not present), for subjects with best overall response of SD or better. |
Time Frame | Up to 54 months |
Outcome Measure Data
Analysis Population Description |
---|
The Efficacy Evaluable Population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab). Number analyzed indicated participants analyzed in the respective tumor type. The median time and the 90% CI were estimated using Kaplan-Meier method. |
Arm/Group Title | Epacadostat 100 mg BID+ Pembrolizumab 200 mg Q3W |
---|---|
Arm/Group Description | Epacadostat 100 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 200 mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. |
Measure Participants | 191 |
Hepatocellular Carcinoma |
10.38
|
Triple Negative Breast Cancer |
11.47
|
Immune Checkpoint-naïve Melanoma |
30.29
|
Relapsed Melanoma |
4.21
|
NSCLC Total |
14.42
|
Renal Cell Carcinoma |
13.39
|
Squamous Cell Carcinoma of the Head and Neck |
9.18
|
Transitional Cell Carcinoma of the GU Tract |
15.36
|
Ovarian Cancer |
5.08
|
Gastric Cancer |
NA
|
MSI high Colorectal Cancer |
NA
|
DLBCL |
7.29
|
Title | Phase 2: Overall Survival (OS) |
---|---|
Description | Overall survival is determined from the date of first dose until death due to any cause. |
Time Frame | Up to 54 months |
Outcome Measure Data
Analysis Population Description |
---|
The Efficacy Evaluable Population included all participants enrolled in the study who received at least 1 dose of study drug. Number analyzed indicated participants analyzed in the respective tumor type. The median time and the 90% CI were estimated using Kaplan-Meier method. |
Arm/Group Title | Epacadostat 100 mg BID+ Pembrolizumab 200 mg Q3W |
---|---|
Arm/Group Description | Epacadostat 100 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 200 mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. |
Measure Participants | 382 |
Hepatocellular Carcinoma |
NA
|
Triple Negative Breast Cancer |
5.16
|
Immune Checkpoint-naïve Melanoma |
NA
|
Primary Refractory Melanoma |
NA
|
Relapsed Melanoma |
NA
|
NSCLC |
14.62
|
Renal Cell Carcinoma |
NA
|
Squamous Cell Carcinoma of the Head and Neck |
8.34
|
Transitional Cell Carcinoma of the GU Tract |
13.44
|
Ovarian Cancer |
13.11
|
Gastric Cancer |
4.04
|
MSI high Colorectal Cancer |
NA
|
DLBCL |
11.79
|
Title | Phase 2: Ordinal Categorical Response Score |
---|---|
Description | Ordinal categorical response score, determined by radiographic disease assessments per irRECIST v1.1. The 5-category ordinal response endpoint is determined at a given timepoint by classifying response into one of the following groups: 1 = Complete response per irRECIST v1.1 2 = Very good response, defined as > 60% tumor reduction 3 = Minor response, defined as > 30% to ≤ 60% tumor reduction 4 = Stable disease per irRECIST v1.1 5 = Progressive disease per irRECIST v1.1 |
Time Frame | Up to 54 months |
Outcome Measure Data
Analysis Population Description |
---|
The Efficacy Evaluable Population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab). Number analyzed indicated participants analyzed in the respective tumor type. |
Arm/Group Title | Epacadostat 100 mg BID+ Pembrolizumab 200 mg Q3W |
---|---|
Arm/Group Description | Epacadostat 100 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 200 mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. |
Measure Participants | 382 |
Complete Response - Score 1 |
0
0%
|
Very Good Response - Score 2 |
2
50%
|
Minor Response - Score 3 |
2
50%
|
Stable Disease - Score 4 |
11
275%
|
Progressive Disease - Score 5 |
8
200%
|
Unable to Evaluable |
1
25%
|
Complete Response - Score 1 |
1
25%
|
Very Good Response - Score 2 |
1
25%
|
Minor Response - Score 3 |
2
50%
|
Stable Disease - Score 4 |
7
175%
|
Progressive Disease - Score 5 |
19
475%
|
Unable to Evaluable |
6
150%
|
Complete Response - Score 1 |
3
75%
|
Very Good Response - Score 2 |
17
425%
|
Minor Response - Score 3 |
6
150%
|
Stable Disease - Score 4 |
5
125%
|
Progressive Disease - Score 5 |
10
250%
|
Unable to Evaluable |
2
50%
|
Complete Response - Score 1 |
0
0%
|
Very Good Response - Score 2 |
0
0%
|
Minor Response - Score 3 |
0
0%
|
Stable Disease - Score 4 |
0
0%
|
Progressive Disease - Score 5 |
2
50%
|
Unable to Evaluable |
1
25%
|
Complete Response - Score 1 |
3
75%
|
Very Good Response - Score 2 |
4
100%
|
Minor Response - Score 3 |
5
125%
|
Stable Disease - Score 4 |
8
200%
|
Progressive Disease - Score 5 |
10
250%
|
Unable to Evaluable |
6
150%
|
Complete Response - Score 1 |
4
100%
|
Very Good Response - Score 2 |
3
75%
|
Minor Response - Score 3 |
8
200%
|
Stable Disease - Score 4 |
15
375%
|
Progressive Disease - Score 5 |
24
600%
|
Unable to Evaluable |
4
100%
|
Complete Response - Score 1 |
2
50%
|
Very Good Response - Score 2 |
6
150%
|
Minor Response - Score 3 |
4
100%
|
Stable Disease - Score 4 |
10
250%
|
Progressive Disease - Score 5 |
13
325%
|
Unable to Evaluable |
2
50%
|
Complete Response - Score 1 |
3
75%
|
Very Good Response - Score 2 |
4
100%
|
Minor Response - Score 3 |
5
125%
|
Stable Disease - Score 4 |
8
200%
|
Progressive Disease - Score 5 |
10
250%
|
Unable to Evaluable |
6
150%
|
Complete Response - Score 1 |
2
50%
|
Very Good Response - Score 2 |
4
100%
|
Minor Response - Score 3 |
5
125%
|
Stable Disease - Score 4 |
10
250%
|
Progressive Disease - Score 5 |
11
275%
|
Unable to Evaluable |
4
100%
|
Complete Response - Score 1 |
1
25%
|
Very Good Response - Score 2 |
0
0%
|
Minor Response - Score 3 |
2
50%
|
Stable Disease - Score 4 |
11
275%
|
Progressive Disease - Score 5 |
16
400%
|
Unable to Evaluable |
7
175%
|
Complete Response - Score 1 |
0
0%
|
Very Good Response - Score 2 |
1
25%
|
Minor Response - Score 3 |
5
125%
|
Stable Disease - Score 4 |
1
25%
|
Progressive Disease - Score 5 |
11
275%
|
Unable to Evaluable |
9
225%
|
Complete Response - Score 1 |
1
25%
|
Very Good Response - Score 2 |
3
75%
|
Minor Response - Score 3 |
3
75%
|
Stable Disease - Score 4 |
3
75%
|
Progressive Disease - Score 5 |
5
125%
|
Unable to Evaluable |
1
25%
|
Title | Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events |
---|---|
Description | |
Time Frame | Up to 54 months |
Outcome Measure Data
Analysis Population Description |
---|
The safety evaluable population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab). Treatment groups for this population were determined according to the actual treatment the participant receives on Day 1. All safety analyses were conducted using the safety evaluable population. |
Arm/Group Title | Phase 2: Epacadostat 100 mg BID |
---|---|
Arm/Group Description | Epacadostat 100 mg tablet orally BID in combination with pembrolizumab 200 mg intravenously every 3 weeks (Q3W). |
Measure Participants | 382 |
Treatment-Emergent Adverse Events (TEAE) |
100
2500%
|
Serious Treatment-Emergent Adverse Events |
51.0
1275%
|
Adverse Events
Time Frame | Approximately 54 months | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | The safety evaluable population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab). | |||||||||||
Arm/Group Title | Phase 1: Epacadostat 25 mg BID | Phase 1: Epacadostat 50 MG BID | Phase 1: Epacadostat 100 MG BID | Phase 1: Epacadostat 300 MG BID | Phase 2: Epacadostat 100 MG BID | Total | ||||||
Arm/Group Description | Epacadostat 25 mg tablet orally twice daily (BID) starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. | Epacadostat 50 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg or 200mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1. | Epacadostat 100 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg or 200mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1 | Epacadostat 300 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg or 200mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1 | Epacadostat 100 mg tablet orally BID in combination with pembrolizumab 200 mg intravenously every 3 weeks (Q3W). | Total | ||||||
All Cause Mortality |
||||||||||||
Phase 1: Epacadostat 25 mg BID | Phase 1: Epacadostat 50 MG BID | Phase 1: Epacadostat 100 MG BID | Phase 1: Epacadostat 300 MG BID | Phase 2: Epacadostat 100 MG BID | Total | |||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 2/4 (50%) | 13/20 (65%) | 12/18 (66.7%) | 14/20 (70%) | 209/382 (54.7%) | 250/444 (56.3%) | ||||||
Serious Adverse Events |
||||||||||||
Phase 1: Epacadostat 25 mg BID | Phase 1: Epacadostat 50 MG BID | Phase 1: Epacadostat 100 MG BID | Phase 1: Epacadostat 300 MG BID | Phase 2: Epacadostat 100 MG BID | Total | |||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/4 (0%) | 8/20 (40%) | 9/18 (50%) | 9/20 (45%) | 195/382 (51%) | 221/444 (49.8%) | ||||||
Blood and lymphatic system disorders | ||||||||||||
Anaemia | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 5/382 (1.3%) | 5 | 6/444 (1.4%) | 6 |
Lymphadenopathy | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Thrombocytopenia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 2 | 1/444 (0.2%) | 2 |
Cardiac disorders | ||||||||||||
Acute coronary syndrome | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Acute myocardial infarction | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Atrial fibrillation | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 2 | 1/444 (0.2%) | 2 |
Atrial flutter | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Cardiac arrest | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Cardiac failure | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Cardiac failure congestive | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Cardiac tamponade | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 2/444 (0.5%) | 2 |
Myocardial infarction | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 3/382 (0.8%) | 3 | 3/444 (0.7%) | 3 |
Myocarditis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Pericardial effusion | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 6/382 (1.6%) | 6 | 6/444 (1.4%) | 6 |
Pulseless electrical activity | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Sinus bradycardia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Tachycardia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Endocrine disorders | ||||||||||||
Hypercalcaemia of malignancy | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Eye disorders | ||||||||||||
Macular degeneration | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Gastrointestinal disorders | ||||||||||||
Abdominal distension | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Abdominal pain | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 12/382 (3.1%) | 13 | 14/444 (3.2%) | 15 |
Abdominal pain upper | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Ascites | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 2/444 (0.5%) | 2 |
Colitis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 6/382 (1.6%) | 6 | 7/444 (1.6%) | 7 |
Constipation | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 4/382 (1%) | 4 | 5/444 (1.1%) | 5 |
Diarrhoea | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 5/382 (1.3%) | 5 | 6/444 (1.4%) | 6 |
Diverticulum intestinal haemorrhagic | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Duodenal ulcer haemorrhage | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Duodenitis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Gastrointestinal haemorrhage | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Gastrointestinal vascular malformation haemorrhagic | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Gastrointestinal wall thickening | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Gastrooesophageal reflux disease | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Intestinal perforation | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Lower gastrointestinal haemorrhage | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Nausea | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 12/382 (3.1%) | 13 | 13/444 (2.9%) | 14 |
Pancreatitis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Rectal haemorrhage | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 2/444 (0.5%) | 2 |
Retching | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Retroperitoneal haemorrhage | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Small intestinal obstruction | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 11/382 (2.9%) | 12 | 11/444 (2.5%) | 12 |
Volvulus | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Vomiting | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 9/382 (2.4%) | 10 | 10/444 (2.3%) | 11 |
General disorders | ||||||||||||
Asthenia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 2/444 (0.5%) | 2 |
Chest pain | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Death | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 2/444 (0.5%) | 2 |
Disease progression | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 9/382 (2.4%) | 9 | 10/444 (2.3%) | 10 |
Facial pain | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Fatigue | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 4/382 (1%) | 4 | 4/444 (0.9%) | 4 |
Non-cardiac chest pain | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 3/382 (0.8%) | 3 | 3/444 (0.7%) | 3 |
Oedema | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Pain | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 2/444 (0.5%) | 2 |
Physical deconditioning | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Pyrexia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 6/382 (1.6%) | 6 | 6/444 (1.4%) | 6 |
Hepatobiliary disorders | ||||||||||||
Acute hepatic failure | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Autoimmune hepatitis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 2/444 (0.5%) | 2 |
Bile duct obstruction | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Bile duct stenosis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Cholecystitis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Hepatic pain | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Hepatorenal syndrome | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Hyperbilirubinaemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Immune-mediated hepatitis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 2/444 (0.5%) | 2 |
Infections and infestations | ||||||||||||
Arthritis bacterial | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Bacteraemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 2/444 (0.5%) | 2 |
Cellulitis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Cellulitis of male external genital organ | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Clostridium difficile colitis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 2/444 (0.5%) | 2 |
Clostridium difficile infection | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Cystitis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Diverticulitis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Enterobacter bacteraemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Gastroenteritis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Gastroenteritis viral | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Influenza | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 3/382 (0.8%) | 3 | 3/444 (0.7%) | 3 |
Meningitis aseptic | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Pneumonia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 15/382 (3.9%) | 16 | 16/444 (3.6%) | 17 |
Pneumonia bacterial | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Pyelonephritis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 3 | 2/444 (0.5%) | 3 |
Pyelonephritis acute | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Renal abscess | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Respiratory syncytial virus infection | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Sepsis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 2/20 (10%) | 4 | 8/382 (2.1%) | 8 | 10/444 (2.3%) | 12 |
Upper respiratory tract infection | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 2 | 1/444 (0.2%) | 2 |
Urinary tract infection | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 6/382 (1.6%) | 6 | 6/444 (1.4%) | 6 |
Urinary tract infection bacterial | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Urosepsis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 3/382 (0.8%) | 3 | 3/444 (0.7%) | 3 |
Vestibular neuronitis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Wound infection | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Injury, poisoning and procedural complications | ||||||||||||
Craniocerebral injury | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Fall | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 3/382 (0.8%) | 3 | 3/444 (0.7%) | 3 |
Femoral neck fracture | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Femur fracture | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Hip fracture | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Infusion related reaction | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Pelvic fracture | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Subdural haematoma | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Urinary tract stoma complication | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Investigations | ||||||||||||
Blood creatinine increased | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Ejection fraction decreased | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
White blood cell count increased | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Metabolism and nutrition disorders | ||||||||||||
Adult failure to thrive | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Dehydration | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 6/382 (1.6%) | 6 | 6/444 (1.4%) | 6 |
Failure to thrive | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 5/382 (1.3%) | 5 | 5/444 (1.1%) | 5 |
Hypercalcaemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 2/444 (0.5%) | 2 |
Hyperglycaemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 2/444 (0.5%) | 2 |
Hyperkalaemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 4/382 (1%) | 4 | 4/444 (0.9%) | 4 |
Hypernatraemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Hypoglycaemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Hypokalaemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 3 | 2/444 (0.5%) | 3 |
Hyponatraemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 3/382 (0.8%) | 4 | 3/444 (0.7%) | 4 |
Malnutrition | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Musculoskeletal and connective tissue disorders | ||||||||||||
Arthralgia | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Back pain | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 3/382 (0.8%) | 3 | 3/444 (0.7%) | 3 |
Flank pain | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 2/444 (0.5%) | 2 |
Gouty arthritis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Muscular weakness | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Myositis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Neck pain | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Osteoarthritis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Pain in extremity | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
Breast cancer metastatic | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Cancer pain | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 3/382 (0.8%) | 3 | 3/444 (0.7%) | 3 |
Choroid melanoma | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Chronic myeloid leukaemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Diffuse large B-cell lymphoma | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Malignant neoplasm progression | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 33/382 (8.6%) | 33 | 35/444 (7.9%) | 35 |
Malignant pleural effusion | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 2 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 3 |
Metastases to bone | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Metastases to central nervous system | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 3/382 (0.8%) | 3 | 3/444 (0.7%) | 3 |
Metastases to peritoneum | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Metastases to spine | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Metastatic lymphoma | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Metastatic squamous cell carcinoma | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Neoplasm progression | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Non-small cell lung cancer | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Non-small cell lung cancer stage I | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Tumour haemorrhage | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Tumour pain | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 2 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 2 |
Nervous system disorders | ||||||||||||
Aphasia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Brain oedema | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 1/382 (0.3%) | 2 | 2/444 (0.5%) | 3 |
Cognitive disorder | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Cranial nerve disorder | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Encephalopathy | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Generalised tonic-clonic seizure | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Haemorrhage intracranial | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Headache | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Hemiparesis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 3/382 (0.8%) | 3 | 3/444 (0.7%) | 3 |
Memory impairment | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Nervous system disorder | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Peripheral sensory neuropathy | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Seizure | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Spinal cord haemorrhage | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Syncope | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 3/382 (0.8%) | 3 | 3/444 (0.7%) | 3 |
Transient ischaemic attack | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Product Issues | ||||||||||||
Device occlusion | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Psychiatric disorders | ||||||||||||
Anxiety | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Confusional state | 0/4 (0%) | 0 | 1/20 (5%) | 2 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 3 |
Delirium | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 2/444 (0.5%) | 2 |
Mental status changes | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Psychotic disorder | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Renal and urinary disorders | ||||||||||||
Acute kidney injury | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 7/382 (1.8%) | 8 | 7/444 (1.6%) | 8 |
Chronic kidney disease | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Hydronephrosis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 2/444 (0.5%) | 2 |
Nephrolithiasis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Polyuria | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Ureteric obstruction | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Ureterolithiasis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Urinary retention | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Urinary tract obstruction | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Reproductive system and breast disorders | ||||||||||||
Scrotal oedema | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||||||||||||
Acute respiratory failure | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 5/382 (1.3%) | 6 | 5/444 (1.1%) | 6 |
Atelectasis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Bronchial obstruction | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Chronic obstructive pulmonary disease | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 5 | 2/444 (0.5%) | 5 |
Cough | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Dyspnoea | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 9/382 (2.4%) | 9 | 11/444 (2.5%) | 11 |
Haemoptysis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Hypoxia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 4/382 (1%) | 4 | 4/444 (0.9%) | 4 |
Laryngeal haemorrhage | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Pharyngeal haemorrhage | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Pleural effusion | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 11/382 (2.9%) | 11 | 12/444 (2.7%) | 12 |
Pneumonia aspiration | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 4/382 (1%) | 4 | 5/444 (1.1%) | 5 |
Pneumonitis | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 4/382 (1%) | 4 | 5/444 (1.1%) | 5 |
Pneumothorax | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Productive cough | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Pulmonary embolism | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 7/382 (1.8%) | 7 | 7/444 (1.6%) | 7 |
Respiratory arrest | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Respiratory failure | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 5/382 (1.3%) | 5 | 5/444 (1.1%) | 5 |
Stridor | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Skin and subcutaneous tissue disorders | ||||||||||||
Palmar-plantar erythrodysaesthesia syndrome | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Rash | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Vascular disorders | ||||||||||||
Deep vein thrombosis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 3/382 (0.8%) | 3 | 4/444 (0.9%) | 4 |
Haemorrhage | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Hypotension | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 5/382 (1.3%) | 6 | 6/444 (1.4%) | 7 |
Hypovolaemic shock | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Superior vena cava syndrome | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Thrombosis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 1/444 (0.2%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||||
Phase 1: Epacadostat 25 mg BID | Phase 1: Epacadostat 50 MG BID | Phase 1: Epacadostat 100 MG BID | Phase 1: Epacadostat 300 MG BID | Phase 2: Epacadostat 100 MG BID | Total | |||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 4/4 (100%) | 18/20 (90%) | 17/18 (94.4%) | 20/20 (100%) | 375/382 (98.2%) | 434/444 (97.7%) | ||||||
Blood and lymphatic system disorders | ||||||||||||
Anaemia | 0/4 (0%) | 0 | 2/20 (10%) | 3 | 2/18 (11.1%) | 6 | 3/20 (15%) | 4 | 48/382 (12.6%) | 65 | 55/444 (12.4%) | 78 |
Increased tendency to bruise | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 3/382 (0.8%) | 3 | 4/444 (0.9%) | 4 |
Iron deficiency anaemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Lymphadenitis | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Neutropenia | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 4/382 (1%) | 6 | 5/444 (1.1%) | 7 |
Thrombocytopenia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 4/382 (1%) | 5 | 5/444 (1.1%) | 6 |
Cardiac disorders | ||||||||||||
Atrial fibrillation | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 6/382 (1.6%) | 7 | 7/444 (1.6%) | 8 |
Bradycardia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Sinus tachycardia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 5/382 (1.3%) | 6 | 6/444 (1.4%) | 7 |
Tachycardia | 0/4 (0%) | 0 | 2/20 (10%) | 2 | 3/18 (16.7%) | 4 | 0/20 (0%) | 0 | 11/382 (2.9%) | 13 | 16/444 (3.6%) | 19 |
Ear and labyrinth disorders | ||||||||||||
Ear discomfort | 1/4 (25%) | 1 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 3/382 (0.8%) | 3 | 5/444 (1.1%) | 5 |
Hypoacusis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 | 1/382 (0.3%) | 1 | 3/444 (0.7%) | 3 |
Tinnitus | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 4/382 (1%) | 5 | 5/444 (1.1%) | 6 |
Vertigo | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 3/382 (0.8%) | 3 | 4/444 (0.9%) | 4 |
Endocrine disorders | ||||||||||||
Hypogonadism | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Hypothalamo-pituitary disorder | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Hypothyroidism | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 2/20 (10%) | 2 | 29/382 (7.6%) | 30 | 32/444 (7.2%) | 33 |
Eye disorders | ||||||||||||
Diplopia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 3/382 (0.8%) | 3 | 4/444 (0.9%) | 4 |
Dry eye | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 4/382 (1%) | 4 | 5/444 (1.1%) | 5 |
Eye pain | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Eye pruritus | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 2/382 (0.5%) | 2 | 4/444 (0.9%) | 4 |
Lacrimation increased | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Ocular hyperaemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Vision blurred | 0/4 (0%) | 0 | 2/20 (10%) | 2 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 14/382 (3.7%) | 14 | 16/444 (3.6%) | 16 |
Visual acuity reduced | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Vitreous floaters | 0/4 (0%) | 0 | 2/20 (10%) | 2 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 3/382 (0.8%) | 3 | 5/444 (1.1%) | 5 |
Xerophthalmia | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Gastrointestinal disorders | ||||||||||||
Abdominal discomfort | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 11/382 (2.9%) | 12 | 12/444 (2.7%) | 13 |
Abdominal distension | 0/4 (0%) | 0 | 3/20 (15%) | 3 | 0/18 (0%) | 0 | 3/20 (15%) | 3 | 19/382 (5%) | 19 | 25/444 (5.6%) | 25 |
Abdominal pain | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 2/18 (11.1%) | 3 | 3/20 (15%) | 4 | 53/382 (13.9%) | 60 | 59/444 (13.3%) | 68 |
Abdominal pain lower | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 6/382 (1.6%) | 6 | 7/444 (1.6%) | 7 |
Abdominal pain upper | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 23/382 (6%) | 25 | 25/444 (5.6%) | 27 |
Cheilitis | 1/4 (25%) | 2 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 3 |
Constipation | 3/4 (75%) | 4 | 8/20 (40%) | 13 | 4/18 (22.2%) | 4 | 3/20 (15%) | 5 | 86/382 (22.5%) | 94 | 104/444 (23.4%) | 120 |
Diarrhoea | 3/4 (75%) | 6 | 5/20 (25%) | 9 | 7/18 (38.9%) | 12 | 5/20 (25%) | 10 | 99/382 (25.9%) | 142 | 119/444 (26.8%) | 179 |
Dry mouth | 1/4 (25%) | 1 | 2/20 (10%) | 2 | 4/18 (22.2%) | 4 | 2/20 (10%) | 2 | 24/382 (6.3%) | 26 | 33/444 (7.4%) | 35 |
Dyspepsia | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 11/382 (2.9%) | 12 | 12/444 (2.7%) | 13 |
Dysphagia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 13/382 (3.4%) | 13 | 14/444 (3.2%) | 14 |
Epigastric discomfort | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 | 0/382 (0%) | 0 | 2/444 (0.5%) | 2 |
Faeces hard | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Flatulence | 1/4 (25%) | 1 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 10/382 (2.6%) | 12 | 12/444 (2.7%) | 14 |
Gastritis | 0/4 (0%) | 0 | 1/20 (5%) | 2 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 3 |
Gastrooesophageal reflux disease | 1/4 (25%) | 2 | 2/20 (10%) | 2 | 1/18 (5.6%) | 1 | 2/20 (10%) | 3 | 13/382 (3.4%) | 13 | 19/444 (4.3%) | 21 |
Glossodynia | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Hypoaesthesia oral | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Large intestine polyp | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Mouth haemorrhage | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Mouth ulceration | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Nausea | 3/4 (75%) | 6 | 9/20 (45%) | 20 | 5/18 (27.8%) | 5 | 11/20 (55%) | 18 | 115/382 (30.1%) | 143 | 143/444 (32.2%) | 192 |
Odynophagia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 4/382 (1%) | 4 | 5/444 (1.1%) | 5 |
Oesophagitis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 4/382 (1%) | 4 | 5/444 (1.1%) | 5 |
Oral disorder | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Stomatitis | 2/4 (50%) | 3 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 3 | 11/382 (2.9%) | 13 | 15/444 (3.4%) | 20 |
Toothache | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 5/382 (1.3%) | 5 | 7/444 (1.6%) | 7 |
Upper gastrointestinal haemorrhage | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Vomiting | 1/4 (25%) | 2 | 4/20 (20%) | 5 | 4/18 (22.2%) | 8 | 10/20 (50%) | 13 | 78/382 (20.4%) | 99 | 97/444 (21.8%) | 127 |
General disorders | ||||||||||||
Asthenia | 1/4 (25%) | 1 | 2/20 (10%) | 3 | 1/18 (5.6%) | 1 | 4/20 (20%) | 4 | 27/382 (7.1%) | 28 | 35/444 (7.9%) | 37 |
Chest discomfort | 1/4 (25%) | 1 | 2/20 (10%) | 2 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 7/382 (1.8%) | 7 | 10/444 (2.3%) | 10 |
Chills | 0/4 (0%) | 0 | 4/20 (20%) | 4 | 2/18 (11.1%) | 3 | 3/20 (15%) | 3 | 36/382 (9.4%) | 40 | 45/444 (10.1%) | 50 |
Early satiety | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 3/382 (0.8%) | 3 | 4/444 (0.9%) | 4 |
Face oedema | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Fatigue | 3/4 (75%) | 5 | 13/20 (65%) | 17 | 9/18 (50%) | 10 | 13/20 (65%) | 20 | 185/382 (48.4%) | 220 | 223/444 (50.2%) | 272 |
Foreign body reaction | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Influenza like illness | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 15/382 (3.9%) | 15 | 17/444 (3.8%) | 17 |
Malaise | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 4/382 (1%) | 4 | 5/444 (1.1%) | 5 |
Mass | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Medical device pain | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Mucosal inflammation | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Non-cardiac chest pain | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 2/18 (11.1%) | 2 | 0/20 (0%) | 0 | 31/382 (8.1%) | 32 | 34/444 (7.7%) | 35 |
Oedema | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 | 5/382 (1.3%) | 5 | 7/444 (1.6%) | 7 |
Oedema peripheral | 1/4 (25%) | 1 | 3/20 (15%) | 4 | 3/18 (16.7%) | 5 | 2/20 (10%) | 2 | 40/382 (10.5%) | 46 | 49/444 (11%) | 58 |
Pain | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 2/18 (11.1%) | 3 | 1/20 (5%) | 1 | 17/382 (4.5%) | 19 | 21/444 (4.7%) | 24 |
Peripheral swelling | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 8/382 (2.1%) | 8 | 10/444 (2.3%) | 10 |
Pyrexia | 0/4 (0%) | 0 | 3/20 (15%) | 5 | 3/18 (16.7%) | 4 | 9/20 (45%) | 10 | 58/382 (15.2%) | 74 | 73/444 (16.4%) | 93 |
Swelling | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Swelling face | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Temperature intolerance | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 3/382 (0.8%) | 3 | 4/444 (0.9%) | 4 |
Hepatobiliary disorders | ||||||||||||
Hyperbilirubinaemia | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Immune system disorders | ||||||||||||
Multiple allergies | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 2/382 (0.5%) | 2 | 4/444 (0.9%) | 4 |
Seasonal allergy | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 7/382 (1.8%) | 7 | 9/444 (2%) | 9 |
Infections and infestations | ||||||||||||
Acute sinusitis | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Body tinea | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Bronchitis | 1/4 (25%) | 1 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 9/382 (2.4%) | 9 | 11/444 (2.5%) | 11 |
Candida infection | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 6/382 (1.6%) | 6 | 8/444 (1.8%) | 8 |
Conjunctivitis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Cystitis | 0/4 (0%) | 0 | 2/20 (10%) | 2 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 4/444 (0.9%) | 4 |
Fungal infection | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Gastroenteritis | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Herpes zoster | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 5/382 (1.3%) | 5 | 7/444 (1.6%) | 7 |
Influenza | 1/4 (25%) | 2 | 1/20 (5%) | 2 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 9/382 (2.4%) | 11 | 11/444 (2.5%) | 15 |
Lower respiratory tract infection | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Nasopharyngitis | 1/4 (25%) | 1 | 4/20 (20%) | 12 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 24/382 (6.3%) | 24 | 30/444 (6.8%) | 38 |
Onychomycosis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Oral herpes | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 2 | 0/20 (0%) | 0 | 4/382 (1%) | 4 | 5/444 (1.1%) | 6 |
Pneumonia | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 10/382 (2.6%) | 11 | 12/444 (2.7%) | 13 |
Postoperative wound infection | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Rash pustular | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Rhinitis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 2 | 3/382 (0.8%) | 3 | 4/444 (0.9%) | 5 |
Sinusitis | 0/4 (0%) | 0 | 2/20 (10%) | 2 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 21/382 (5.5%) | 25 | 23/444 (5.2%) | 27 |
Tinea pedis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Upper respiratory tract infection | 0/4 (0%) | 0 | 3/20 (15%) | 6 | 2/18 (11.1%) | 2 | 2/20 (10%) | 2 | 31/382 (8.1%) | 38 | 38/444 (8.6%) | 48 |
Urinary tract infection | 1/4 (25%) | 2 | 2/20 (10%) | 8 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 28/382 (7.3%) | 36 | 32/444 (7.2%) | 47 |
Viral pharyngitis | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Injury, poisoning and procedural complications | ||||||||||||
Arthropod bite | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 | 2/382 (0.5%) | 2 | 4/444 (0.9%) | 4 |
Epicondylitis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Fall | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 2/18 (11.1%) | 2 | 0/20 (0%) | 0 | 23/382 (6%) | 24 | 26/444 (5.9%) | 27 |
Hip fracture | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Incision site pain | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Incision site pruritus | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Infusion related reaction | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Joint injury | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Ligament sprain | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Procedural pain | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 7/382 (1.8%) | 7 | 9/444 (2%) | 9 |
Skin laceration | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 5/382 (1.3%) | 5 | 6/444 (1.4%) | 6 |
Stoma site haemorrhage | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Tooth fracture | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Wrist fracture | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Investigations | ||||||||||||
Alanine aminotransferase increased | 0/4 (0%) | 0 | 2/20 (10%) | 3 | 3/18 (16.7%) | 4 | 1/20 (5%) | 1 | 36/382 (9.4%) | 46 | 42/444 (9.5%) | 54 |
Amylase increased | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 1/18 (5.6%) | 5 | 2/20 (10%) | 3 | 35/382 (9.2%) | 45 | 39/444 (8.8%) | 54 |
Aspartate aminotransferase increased | 0/4 (0%) | 0 | 2/20 (10%) | 3 | 4/18 (22.2%) | 6 | 1/20 (5%) | 1 | 44/382 (11.5%) | 56 | 51/444 (11.5%) | 66 |
Blood alkaline phosphatase increased | 0/4 (0%) | 0 | 2/20 (10%) | 2 | 2/18 (11.1%) | 2 | 1/20 (5%) | 1 | 31/382 (8.1%) | 37 | 36/444 (8.1%) | 42 |
Blood bilirubin increased | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 7/382 (1.8%) | 7 | 8/444 (1.8%) | 8 |
Blood calcium decreased | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Blood creatinine increased | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 2 | 25/382 (6.5%) | 29 | 27/444 (6.1%) | 32 |
Blood iron decreased | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 2/18 (11.1%) | 2 | 0/20 (0%) | 0 | 4/382 (1%) | 4 | 6/444 (1.4%) | 6 |
Blood thyroid stimulating hormone increased | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 2 | 0/20 (0%) | 0 | 5/382 (1.3%) | 5 | 6/444 (1.4%) | 7 |
Body temperature increased | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 4/382 (1%) | 4 | 5/444 (1.1%) | 5 |
Electrocardiogram QT prolonged | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Gamma-glutamyltransferase increased | 0/4 (0%) | 0 | 2/20 (10%) | 2 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 3/382 (0.8%) | 3 | 5/444 (1.1%) | 5 |
Lipase decreased | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Lipase increased | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 3/18 (16.7%) | 13 | 3/20 (15%) | 6 | 48/382 (12.6%) | 80 | 54/444 (12.2%) | 99 |
Platelet count decreased | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 2 | 9/382 (2.4%) | 11 | 10/444 (2.3%) | 13 |
Red blood cell count decreased | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 2 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 3 |
Troponin increased | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Weight decreased | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 4/18 (22.2%) | 4 | 1/20 (5%) | 1 | 35/382 (9.2%) | 37 | 40/444 (9%) | 42 |
Weight increased | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 8/382 (2.1%) | 9 | 10/444 (2.3%) | 11 |
White blood cell count decreased | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 14/382 (3.7%) | 16 | 15/444 (3.4%) | 17 |
Metabolism and nutrition disorders | ||||||||||||
Decreased appetite | 0/4 (0%) | 0 | 4/20 (20%) | 4 | 1/18 (5.6%) | 1 | 9/20 (45%) | 9 | 95/382 (24.9%) | 103 | 109/444 (24.5%) | 117 |
Dehydration | 1/4 (25%) | 1 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 32/382 (8.4%) | 34 | 34/444 (7.7%) | 36 |
Hypercalcaemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 | 14/382 (3.7%) | 14 | 16/444 (3.6%) | 16 |
Hyperglycaemia | 0/4 (0%) | 0 | 1/20 (5%) | 2 | 2/18 (11.1%) | 4 | 3/20 (15%) | 5 | 23/382 (6%) | 31 | 29/444 (6.5%) | 42 |
Hyperkalaemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 3/18 (16.7%) | 5 | 2/20 (10%) | 3 | 21/382 (5.5%) | 26 | 26/444 (5.9%) | 34 |
Hypermagnesaemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Hyperphosphataemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 2/382 (0.5%) | 4 | 3/444 (0.7%) | 5 |
Hyperuricaemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 15/382 (3.9%) | 17 | 16/444 (3.6%) | 18 |
Hypoalbuminaemia | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 2/20 (10%) | 2 | 14/382 (3.7%) | 14 | 17/444 (3.8%) | 17 |
Hypocalcaemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 2/20 (10%) | 2 | 9/382 (2.4%) | 9 | 11/444 (2.5%) | 11 |
Hypoglycaemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 2 | 1/20 (5%) | 1 | 6/382 (1.6%) | 6 | 8/444 (1.8%) | 9 |
Hypokalaemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 2/18 (11.1%) | 2 | 2/20 (10%) | 2 | 30/382 (7.9%) | 39 | 34/444 (7.7%) | 43 |
Hypomagnesaemia | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 12/382 (3.1%) | 17 | 14/444 (3.2%) | 19 |
Hyponatraemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 3/18 (16.7%) | 5 | 1/20 (5%) | 1 | 39/382 (10.2%) | 57 | 43/444 (9.7%) | 63 |
Hypophosphataemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 2/20 (10%) | 6 | 17/382 (4.5%) | 25 | 19/444 (4.3%) | 31 |
Hypovolaemia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Vitamin D deficiency | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Musculoskeletal and connective tissue disorders | ||||||||||||
Arthralgia | 4/4 (100%) | 7 | 9/20 (45%) | 12 | 4/18 (22.2%) | 6 | 6/20 (30%) | 8 | 64/382 (16.8%) | 88 | 87/444 (19.6%) | 121 |
Back pain | 1/4 (25%) | 2 | 4/20 (20%) | 4 | 7/18 (38.9%) | 8 | 5/20 (25%) | 6 | 48/382 (12.6%) | 58 | 65/444 (14.6%) | 78 |
Bursitis | 0/4 (0%) | 0 | 2/20 (10%) | 2 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 2/444 (0.5%) | 2 |
Flank pain | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 1/18 (5.6%) | 1 | 2/20 (10%) | 2 | 17/382 (4.5%) | 19 | 21/444 (4.7%) | 23 |
Groin pain | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 7/382 (1.8%) | 8 | 9/444 (2%) | 10 |
Joint contracture | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Joint swelling | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 4/382 (1%) | 4 | 5/444 (1.1%) | 5 |
Limb discomfort | 0/4 (0%) | 0 | 2/20 (10%) | 2 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 2/444 (0.5%) | 2 |
Muscle spasms | 2/4 (50%) | 2 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 23/382 (6%) | 31 | 25/444 (5.6%) | 33 |
Muscle tightness | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Muscle twitching | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 3/382 (0.8%) | 4 | 4/444 (0.9%) | 5 |
Muscular weakness | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 | 16/382 (4.2%) | 16 | 19/444 (4.3%) | 19 |
Musculoskeletal chest pain | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 | 13/382 (3.4%) | 16 | 15/444 (3.4%) | 18 |
Musculoskeletal pain | 1/4 (25%) | 1 | 3/20 (15%) | 3 | 1/18 (5.6%) | 1 | 3/20 (15%) | 4 | 28/382 (7.3%) | 30 | 36/444 (8.1%) | 39 |
Musculoskeletal stiffness | 0/4 (0%) | 0 | 2/20 (10%) | 3 | 1/18 (5.6%) | 1 | 3/20 (15%) | 3 | 4/382 (1%) | 4 | 10/444 (2.3%) | 11 |
Myalgia | 0/4 (0%) | 0 | 4/20 (20%) | 4 | 3/18 (16.7%) | 3 | 5/20 (25%) | 7 | 22/382 (5.8%) | 25 | 34/444 (7.7%) | 39 |
Neck pain | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 | 12/382 (3.1%) | 12 | 14/444 (3.2%) | 14 |
Osteoporosis | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Pain in extremity | 3/4 (75%) | 4 | 3/20 (15%) | 4 | 0/18 (0%) | 0 | 5/20 (25%) | 7 | 40/382 (10.5%) | 45 | 51/444 (11.5%) | 60 |
Trismus | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
Seborrhoeic keratosis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Nervous system disorders | ||||||||||||
Amnesia | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Ataxia | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Balance disorder | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 2/18 (11.1%) | 2 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 3/444 (0.7%) | 3 |
Cerebral cyst | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Disturbance in attention | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Dizziness | 0/4 (0%) | 0 | 5/20 (25%) | 9 | 2/18 (11.1%) | 2 | 3/20 (15%) | 4 | 40/382 (10.5%) | 49 | 50/444 (11.3%) | 64 |
Dizziness postural | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 2 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 4 |
Dysgeusia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 2/18 (11.1%) | 2 | 0/20 (0%) | 0 | 8/382 (2.1%) | 8 | 10/444 (2.3%) | 10 |
Headache | 2/4 (50%) | 4 | 6/20 (30%) | 13 | 1/18 (5.6%) | 1 | 4/20 (20%) | 5 | 58/382 (15.2%) | 77 | 71/444 (16%) | 100 |
Hyperaesthesia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Hypoaesthesia | 0/4 (0%) | 0 | 2/20 (10%) | 2 | 1/18 (5.6%) | 1 | 2/20 (10%) | 3 | 12/382 (3.1%) | 13 | 17/444 (3.8%) | 19 |
Memory impairment | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 7/382 (1.8%) | 8 | 8/444 (1.8%) | 9 |
Migraine | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 3/382 (0.8%) | 3 | 4/444 (0.9%) | 4 |
Neuropathy peripheral | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 14/382 (3.7%) | 14 | 16/444 (3.6%) | 16 |
Paraesthesia | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 9/382 (2.4%) | 10 | 11/444 (2.5%) | 12 |
Peripheral sensory neuropathy | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 3/20 (15%) | 4 | 5/382 (1.3%) | 5 | 8/444 (1.8%) | 9 |
Post herpetic neuralgia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Restless legs syndrome | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Seizure | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Slow speech | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Taste disorder | 1/4 (25%) | 1 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 10/382 (2.6%) | 10 | 12/444 (2.7%) | 12 |
VIth nerve paralysis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Psychiatric disorders | ||||||||||||
Anxiety | 1/4 (25%) | 1 | 2/20 (10%) | 2 | 2/18 (11.1%) | 3 | 3/20 (15%) | 3 | 23/382 (6%) | 24 | 31/444 (7%) | 33 |
Confusional state | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 8/382 (2.1%) | 8 | 9/444 (2%) | 9 |
Depression | 2/4 (50%) | 2 | 2/20 (10%) | 2 | 0/18 (0%) | 0 | 2/20 (10%) | 2 | 18/382 (4.7%) | 20 | 24/444 (5.4%) | 26 |
Insomnia | 2/4 (50%) | 2 | 6/20 (30%) | 6 | 1/18 (5.6%) | 1 | 2/20 (10%) | 2 | 44/382 (11.5%) | 48 | 55/444 (12.4%) | 59 |
Mental status changes | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Renal and urinary disorders | ||||||||||||
Acute kidney injury | 0/4 (0%) | 0 | 1/20 (5%) | 2 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 6/382 (1.6%) | 7 | 7/444 (1.6%) | 9 |
Chromaturia | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Dysuria | 0/4 (0%) | 0 | 2/20 (10%) | 2 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 5/382 (1.3%) | 5 | 8/444 (1.8%) | 8 |
Haematuria | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 6/382 (1.6%) | 8 | 7/444 (1.6%) | 9 |
Micturition urgency | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 6/382 (1.6%) | 7 | 7/444 (1.6%) | 8 |
Nocturia | 0/4 (0%) | 0 | 2/20 (10%) | 2 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 4/382 (1%) | 4 | 6/444 (1.4%) | 6 |
Pollakiuria | 0/4 (0%) | 0 | 2/20 (10%) | 2 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 14/382 (3.7%) | 16 | 17/444 (3.8%) | 19 |
Ureteric obstruction | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Urinary retention | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 4/382 (1%) | 4 | 6/444 (1.4%) | 6 |
Reproductive system and breast disorders | ||||||||||||
Balanoposthitis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Erectile dysfunction | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Nipple pain | 0/4 (0%) | 0 | 1/20 (5%) | 2 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 2 |
Pelvic pain | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 4/382 (1%) | 4 | 5/444 (1.1%) | 5 |
Vulvovaginal pain | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||||||||||||
Aspiration | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Asthma | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Cough | 3/4 (75%) | 4 | 7/20 (35%) | 9 | 3/18 (16.7%) | 3 | 9/20 (45%) | 9 | 100/382 (26.2%) | 114 | 122/444 (27.5%) | 139 |
Dry throat | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Dysphonia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 | 10/382 (2.6%) | 11 | 12/444 (2.7%) | 13 |
Dyspnoea | 2/4 (50%) | 3 | 2/20 (10%) | 2 | 6/18 (33.3%) | 7 | 5/20 (25%) | 7 | 69/382 (18.1%) | 77 | 84/444 (18.9%) | 96 |
Dyspnoea exertional | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 20/382 (5.2%) | 23 | 22/444 (5%) | 25 |
Epistaxis | 1/4 (25%) | 1 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 12/382 (3.1%) | 13 | 15/444 (3.4%) | 16 |
Haemoptysis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 2/18 (11.1%) | 2 | 0/20 (0%) | 0 | 11/382 (2.9%) | 12 | 13/444 (2.9%) | 14 |
Nasal congestion | 0/4 (0%) | 0 | 2/20 (10%) | 2 | 2/18 (11.1%) | 2 | 1/20 (5%) | 1 | 20/382 (5.2%) | 22 | 25/444 (5.6%) | 27 |
Oropharyngeal pain | 1/4 (25%) | 1 | 1/20 (5%) | 2 | 0/18 (0%) | 0 | 3/20 (15%) | 4 | 19/382 (5%) | 21 | 24/444 (5.4%) | 28 |
Paranasal sinus discomfort | 0/4 (0%) | 0 | 1/20 (5%) | 2 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 3 |
Paranasal sinus hypersecretion | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Pharyngeal paraesthesia | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Pleuritic pain | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Pneumonitis | 0/4 (0%) | 0 | 1/20 (5%) | 2 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 5/382 (1.3%) | 5 | 6/444 (1.4%) | 7 |
Productive cough | 0/4 (0%) | 0 | 3/20 (15%) | 5 | 2/18 (11.1%) | 2 | 1/20 (5%) | 1 | 25/382 (6.5%) | 28 | 31/444 (7%) | 36 |
Pulmonary embolism | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 5/382 (1.3%) | 5 | 6/444 (1.4%) | 6 |
Respiratory tract congestion | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 4/382 (1%) | 4 | 5/444 (1.1%) | 5 |
Rhinitis allergic | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 | 3/382 (0.8%) | 3 | 6/444 (1.4%) | 6 |
Rhinorrhoea | 1/4 (25%) | 1 | 2/20 (10%) | 3 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 8/382 (2.1%) | 8 | 11/444 (2.5%) | 12 |
Sinus congestion | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 2/20 (10%) | 2 | 10/382 (2.6%) | 10 | 13/444 (2.9%) | 13 |
Sinus pain | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Sneezing | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Throat irritation | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Upper-airway cough syndrome | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 1/18 (5.6%) | 1 | 2/20 (10%) | 2 | 10/382 (2.6%) | 10 | 14/444 (3.2%) | 14 |
Wheezing | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 | 16/382 (4.2%) | 18 | 19/444 (4.3%) | 21 |
Skin and subcutaneous tissue disorders | ||||||||||||
Actinic keratosis | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Alopecia | 1/4 (25%) | 1 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 6/382 (1.6%) | 6 | 9/444 (2%) | 9 |
Alopecia areata | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Blister | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Dermatitis acneiform | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Diffuse alopecia | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Dry skin | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 2/18 (11.1%) | 2 | 1/20 (5%) | 1 | 16/382 (4.2%) | 18 | 20/444 (4.5%) | 22 |
Ecchymosis | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 2/444 (0.5%) | 2 |
Eczema | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Erythema | 1/4 (25%) | 3 | 1/20 (5%) | 1 | 1/18 (5.6%) | 3 | 2/20 (10%) | 2 | 8/382 (2.1%) | 9 | 13/444 (2.9%) | 18 |
Erythema multiforme | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Hair colour changes | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Hyperhidrosis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 2/20 (10%) | 2 | 10/382 (2.6%) | 11 | 12/444 (2.7%) | 13 |
Nail bed disorder | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Pain of skin | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Palmar-plantar erythrodysaesthesia syndrome | 0/4 (0%) | 0 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Pruritus | 3/4 (75%) | 4 | 6/20 (30%) | 12 | 2/18 (11.1%) | 2 | 9/20 (45%) | 12 | 78/382 (20.4%) | 96 | 98/444 (22.1%) | 126 |
Rash | 2/4 (50%) | 3 | 6/20 (30%) | 10 | 1/18 (5.6%) | 1 | 6/20 (30%) | 13 | 86/382 (22.5%) | 108 | 101/444 (22.7%) | 135 |
Rash erythematous | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 2 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 4 |
Rash follicular | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Rash maculo-papular | 0/4 (0%) | 0 | 3/20 (15%) | 4 | 0/18 (0%) | 0 | 4/20 (20%) | 5 | 19/382 (5%) | 23 | 26/444 (5.9%) | 32 |
Rash papular | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Rash pruritic | 1/4 (25%) | 1 | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 2/20 (10%) | 11 | 11/382 (2.9%) | 11 | 15/444 (3.4%) | 24 |
Skin discolouration | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Skin disorder | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Skin exfoliation | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Skin lesion | 1/4 (25%) | 1 | 2/20 (10%) | 2 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 8/382 (2.1%) | 10 | 12/444 (2.7%) | 14 |
Skin ulcer | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Vitiligo | 1/4 (25%) | 1 | 2/20 (10%) | 2 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 4/382 (1%) | 4 | 7/444 (1.6%) | 7 |
Xeroderma | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/382 (0.3%) | 1 | 2/444 (0.5%) | 2 |
Vascular disorders | ||||||||||||
Deep vein thrombosis | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Hot flush | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 2/20 (10%) | 2 | 7/382 (1.8%) | 7 | 9/444 (2%) | 9 |
Hypertension | 0/4 (0%) | 0 | 2/20 (10%) | 2 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 9/382 (2.4%) | 9 | 11/444 (2.5%) | 11 |
Hypotension | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 11/382 (2.9%) | 14 | 12/444 (2.7%) | 15 |
Jugular vein thrombosis | 1/4 (25%) | 1 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Lymphoedema | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 2/382 (0.5%) | 2 | 3/444 (0.7%) | 3 |
Phlebitis superficial | 0/4 (0%) | 0 | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/382 (0%) | 0 | 1/444 (0.2%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Clinical Study Agreement
Results Point of Contact
Name/Title | Study Director |
---|---|
Organization | Incyte Corporation |
Phone | 1-855-463-3463 |
medinfo@incyte.com |
- INCB 24360-202/ ECHO-202