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A Study of Epacadostat in Combination With Pembrolizumab and Chemotherapy in Participants With Advanced or Metastatic Solid Tumors (ECHO-207/KEYNOTE-723)

Sponsor
Incyte Corporation (Industry)
Overall Status
Completed
CT.gov ID
NCT03085914
Collaborator
(none)
70
Enrollment
16
Locations
7
Arms
38.4
Actual Duration (Months)
4.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This was an open-label, nonrandomized, Phase 1/2 study designed to determine the safety, tolerability, and efficacy of epacadostat when given in combination with pembrolizumab and 7 different chemotherapy regimens described as Treatment Groups A through G below (see Study Drug and Background Therapies, Dose, and Mode of Administration). Phase 1 consisted of a 3 + 3 + 3 design intended to determine the MTD or PAD of epacadostat when given in combination with pembrolizumab and chemotherapy; efficacy was also explored.

Phase 2 was designed to enroll efficacy expansion cohorts to further evaluate the safety, tolerability, and efficacy of epacadostat at the MTD or PAD (as selected in Phase 1) when given in combination with pembrolizumab and chemotherapy. Each efficacy expansion cohort was to enroll participants with 1 specific type of advanced or metastatic solid tumor. Additional cohorts (ie, the mandatory biopsy cohorts) were designed to evaluate changes in the tumor microenvironment in participants with any advanced or metastatic solid tumor who had progressed on previous therapy with a PD-1 or a PD-L1 inhibitor.

No participants were enrolled in any Phase 2 efficacy expansion cohort, or in any Phase 2 mandatory biopsy cohort receiving Treatment A, B, F, or G. Phase 2 mandatory biopsy cohort participants received Treatments C, D, or E (ie, were included in Treatment Groups C, D, or E). Participants were assigned to a treatment group based on the chemotherapy regimen most appropriate for their tumor type.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
70 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2, Open-Label, Safety, Tolerability, and Efficacy Study of Epacadostat in Combination With Pembrolizumab and Chemotherapy in Subjects With Advanced or Metastatic Solid Tumors (ECHO-207/KEYNOTE-723)
Actual Study Start Date :
May 2, 2017
Actual Primary Completion Date :
Jan 25, 2019
Actual Study Completion Date :
Jul 13, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment Group A

Epacadostat + pembrolizumab + mFOLFOX6 (oxaliplatin, leucovorin, 5-fluorouracil)

Drug: Epacadostat
Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.
Other Names:
  • INCB024360

    • Drug: Pembrolizumab
    Pembrolizumab

    Drug: Oxaliplatin
    Oxaliplatin

    Drug: Leucovorin
    Leucovorin

    Drug: 5-Fluorouracil
    5-Fluorouracil
    Experimental: Treatment Group B

    Epacadostat + pembrolizumab + gemcitabine and nab-paclitaxel

    Drug: Epacadostat
    Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.
    Other Names:
  • INCB024360

    • Drug: Pembrolizumab
    Pembrolizumab

    Drug: Gemcitabine
    Gemcitabine

    Drug: nab-Paclitaxel
    nab-Paclitaxel
    Experimental: Treatment Group C

    Epacadostat + pembrolizumab + carboplatin and paclitaxel

    Drug: Epacadostat
    Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.
    Other Names:
  • INCB024360

    • Drug: Pembrolizumab
    Pembrolizumab

    Drug: Carboplatin
    Carboplatin

    Drug: Paclitaxel
    Paclitaxel
    Experimental: Treatment Group D

    Epacadostat + pembrolizumab + pemetrexed and investigators choice of platinum agent

    Drug: Epacadostat
    Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.
    Other Names:
  • INCB024360

    • Drug: Pembrolizumab
    Pembrolizumab

    Drug: Pemetrexed
    Pemetrexed

    Drug: Carboplatin
    Carboplatin

    Drug: Cisplatin
    Cisplatin

    Drug: Investigator's choice of platinum agent
    Investigator's choice of platinum agent: carboplatin or cisplatin
    Experimental: Treatment Group E

    Epacadostat + pembrolizumab + cyclophosphamide

    Drug: Epacadostat
    Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.
    Other Names:
  • INCB024360

    • Drug: Pembrolizumab
    Pembrolizumab

    Drug: Cyclophosphamide
    Cyclophosphamide
    Experimental: Treatment Group F

    Epacadostat + pembrolizumab + gemcitabine and investigators choice of platinum agent

    Drug: Epacadostat
    Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.
    Other Names:
  • INCB024360

    • Drug: Pembrolizumab
    Pembrolizumab

    Drug: Gemcitabine
    Gemcitabine
    Experimental: Treatment Group G

    Epacadostat + pembrolizumab + investigators choice of platinum agent and 5-fluorouracil

    Drug: Epacadostat
    Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.
    Other Names:
  • INCB024360

    • Drug: Pembrolizumab
    Pembrolizumab

    Drug: Carboplatin
    Carboplatin

    Drug: Cisplatin
    Cisplatin

    Drug: 5-Fluorouracil
    5-FU

    Drug: Investigator's choice of platinum agent
    Investigator's choice of platinum agent: carboplatin or cisplatin

    Outcome Measures

    Primary Outcome Measures

    1. Phases 1 & 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [Up to 21 months]

      A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of epacadostat, pembrolizumab, or chemotherapy. Serious adverse event is defined as an event that meets 1 of the following criteria: is fatal or life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability, incapacity, or a substantial disruption of a person's ability to conduct normal life functions, constitutes a congenital anomaly or birth defect,is a medically important event that may jeopardize the participant or may require medical or surgical intervention to prevent 1 of the outcomes listed above.

    2. Phases 1 and 2: Number of Participants With Dose Limiting Toxicities (DLTs) [28 days]

      A DLT was defined as the occurrence of any of the protocol-specified toxicities occurring up to and including Day 28 for the cohorts where mFOLFOX6 and nab-paclitaxel/gemcitabine are administered and Day 21 for all other chemotherapy regimens in Phase 1, except those with a clear alternative explanation (eg, disease progression) or transient (≤ 72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination.

    3. Phases 1 and 2: Objective Response Rate (ORR) [Up to Week 18]

      ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Histologically or cytologically confirmed diagnosis of selected advanced or metastatic solid tumors.

    • Presence of measurable disease per RECIST v1.1.

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

    Exclusion Criteria:

    • Laboratory and medical history parameters not within the Protocol-defined range.

    • Receipt of anticancer medications or investigational drugs within the Protocol-defined intervals before the first administration of study drug.

    • Previous radiotherapy within 2 weeks of starting study therapy.

    • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

    • Has not recovered to ≤ Grade 1 from toxic effects of previous therapy and/or complications from previous surgical intervention before starting study therapy.

    • Receipt of a live vaccine within 30 days of planned start of study therapy.

    • Active infection requiring systemic therapy.

    • Subjects who have any active or inactive autoimmune disease or syndrome.

    • Women who are pregnant or breastfeeding.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic Arizona Phoenix Arizona United States 85054
    2 University of California San Diego Medical Center, Moores Cancer Center La Jolla California United States 92093
    3 The Angeles Clinic and Research Institute Los Angeles California United States 90025
    4 Mayo Clinic Jacksonville Florida United States 32224
    5 University of Chicago Chicago Illinois United States 60637
    6 Mayo Clinic Rochester Minnesota United States 55905
    7 Washington University School of Medicine Saint Louis Missouri United States 63110
    8 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    9 Carolina Bio-Oncology Institute, PLLC Huntersville North Carolina United States 28078
    10 Oregon Health and Science University Portland Oregon United States 97239
    11 University of Pennsylvania Health System Philadelphia Pennsylvania United States 19104
    12 University of Pittsburgh Cancer Institute Pittsburgh Pennsylvania United States 15237
    13 Tennessee Oncology - Nashville; The Sarah Cannon Research Institute Nashville Tennessee United States 37203
    14 Vanderbilt University; Henry Joyce Cancer Clinic Nashville Tennessee United States 37232
    15 MD Anderson Cancer Center Houston Texas United States 77030
    16 Huntsman Cancer Institute at University of Utah Salt Lake City Utah United States 84112

    Sponsors and Collaborators

    • Incyte Corporation

    Investigators

    • Study Director: Fred Zheng, MD, Incyte Corporation

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Incyte Corporation
    ClinicalTrials.gov Identifier:
    NCT03085914
    Other Study ID Numbers:
    • INCB 24360-207 / ECHO-207
    • 2016-004678-16
    First Posted:
    Mar 21, 2017
    Last Update Posted:
    Aug 5, 2021
    Last Verified:
    Jul 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Incyte Corporation
    solid tumors
    colorectal cancer
    pancreatic ductal adenocarcinoma
    non-small cell lung cancer
    PD-1
    PD-L1
    epacadostat
    IDO inhibitor
    Additional relevant MeSH terms:
    Neoplasms
    Leucovorin
    Gemcitabine
    Paclitaxel
    Albumin-Bound Paclitaxel
    Cyclophosphamide
    Carboplatin
    Pembrolizumab
    Fluorouracil
    Oxaliplatin
    Pemetrexed

    Study Results

    Participant Flow

    Recruitment Details The study was conducted at 9 study sites in the US. Phases 1 and 2 each consisted of Treatment Groups A-G, and every patient in the same group in Phases 1 and 2 received the same dose of epacadostat (100 mg BID oral), pembrolizumab (200 mg IV), and the respective chemotherapy regimens. Data analysis and summarization were performed by treatment group, by combining data of the same group in Phases 1 and 2.
    Pre-assignment Detail A total of 70 participants were enrolled in the study. Study enrollment was permanently discontinued on 25 Oct 2018 as a strategic decision. At the time of data cut-off date of 25 Jan 2019, 11 participants were ongoing on treatment. . Phase 2 consisted of efficacy expansion and Mandatory biopsy cohorts. Phase 2 Efficacy expansion cohorts did not open for enrollment. Phase 2/Mandatory biopsy cohorts opened for enrollment and only groups C, D and E enrolled participants prior to study termination
    Arm/Group Title Group A: Epa + Pembrolizumab +mFOLFOX6 Group B: Epa + Pembrolizumab + Nab-Paclitaxel and Gemcitabine Group C: Epa + Pembrolizumab + Paclitaxel and Carboplatin Group D: Epa + Pembrolizumab + Pemetrexed and Platinum Agent Group E: Epa + Pembrolizumab + Cyclophosphamide Group F: Epa + Pembrolizumab + Gemcitabine and Platinum Agent Group G: Epa + Pembrolizumab + 5-FU and Platinum Agent
    Arm/Group Description Epacadostat (Epa, 100 mg ) oral twice-daily (BID) continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg)administered intravenously (IV) in combination with mFOLFOX6 (oxaliplatin IV + leucovorin IV + 5-fluorouracil (5-FU) IV. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with nab-paclitaxel IV and gemcitabine IV. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) in combination with paclitaxel IV and carboplatin IV. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with pemetrexed IV and Investigator's choice of platinum agent: carboplatin IV or cisplatin IV. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with cyclophosphamide PO. Epa (100mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with gemcitabine IV and Investigator's choice of platinum agent: carboplatin IV or cisplatin IV. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with 5-FU IV and Investigator's choice of platinum agent: carboplatin IV or cisplatin IV.
    Period Title: Overall Study
    STARTED 9 9 11 9 13 8 11
    COMPLETED 0 0 0 0 0 0 0
    NOT COMPLETED 9 9 11 9 13 8 11

    Baseline Characteristics

    Arm/Group Title Group A: Epa + Pembrolizumab + mFOLFOX6 Group B: Epa + Pembrolizumab + Nab-Paclitaxel and Gemcitabine Group C: Epa + Pembrolizumab + Paclitaxel and Carboplatin Group D: Epa + Pembrolizumab + Pemetrexed and Platinum Agent Group E: Epa + Pembrolizumab + Cyclophosphamide Group F: Epa + Pembrolizumab + Gemcitabine and Platinum Agent Group G: Epa + Pembrolizumab + 5-FU and Platinum Agent Total
    Arm/Group Description Epacadostat (Epa) oral twice-daily (BID) continuous daily dosing at the protocol-defined dose in combination with pembrolizumab administered intravenously (IV) in combination with mFOLFOX6 (oxaliplatin IV + leucovorin IV + 5-fluorouracil (5-FU) IV. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with nab-paclitaxel IV and gemcitabine IV. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) in combination with paclitaxel IV and carboplatin IV. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with pemetrexed IV and Investigator's choice of platinum agent: carboplatin IV or cisplatin IV. Epa (100 mg)oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with cyclophosphamide PO. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with gemcitabine IV and Investigator's choice of platinum agent: carboplatin IV or cisplatin IV. Epa (100 mg) oral BID continuousdaily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with 5-FU IV and Investigator's choice of platinum agent: carboplatin IV or cisplatin IV. Total of all reporting groups
    Overall Participants 9 9 11 9 13 8 11 70
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    55.8
    (8.03)
    46.0
    (14.98)
    63.7
    (12.11)
    58.2
    (12.96)
    62.0
    (10.21)
    60.3
    (12.01)
    59.4
    (12.24)
    58.3
    (12.54)
    Sex: Female, Male (Count of Participants)
    Female
    3
    33.3%
    4
    44.4%
    6
    54.5%
    4
    44.4%
    10
    76.9%
    5
    62.5%
    4
    36.4%
    36
    51.4%
    Male
    6
    66.7%
    5
    55.6%
    5
    45.5%
    5
    55.6%
    3
    23.1%
    3
    37.5%
    7
    63.6%
    34
    48.6%
    Race/Ethnicity, Customized (Count of Participants)
    White/Caucasian
    7
    77.8%
    7
    77.8%
    9
    81.8%
    8
    88.9%
    10
    76.9%
    6
    75%
    8
    72.7%
    55
    78.6%
    Black/African-American
    2
    22.2%
    1
    11.1%
    0
    0%
    0
    0%
    1
    7.7%
    0
    0%
    2
    18.2%
    6
    8.6%
    Asian
    0
    0%
    0
    0%
    1
    9.1%
    0
    0%
    0
    0%
    2
    25%
    0
    0%
    3
    4.3%
    Native Hawaiian/Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    0
    0%
    0
    0%
    1
    1.4%
    Other
    0
    0%
    1
    11.1%
    1
    9.1%
    0
    0%
    2
    15.4%
    0
    0%
    1
    9.1%
    5
    7.1%
    Race/Ethnicity, Customized (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    9.1%
    1
    1.4%
    Not Hispanic or Latino
    9
    100%
    9
    100%
    11
    100%
    7
    77.8%
    13
    100%
    8
    100%
    10
    90.9%
    67
    95.7%
    Not Reported
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    0
    0%
    0
    0%
    1
    1.4%
    Unknown
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    0
    0%
    0
    0%
    1
    1.4%

    Outcome Measures

    1. Primary Outcome
    Title Phases 1 & 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
    Description A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of epacadostat, pembrolizumab, or chemotherapy. Serious adverse event is defined as an event that meets 1 of the following criteria: is fatal or life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability, incapacity, or a substantial disruption of a person's ability to conduct normal life functions, constitutes a congenital anomaly or birth defect,is a medically important event that may jeopardize the participant or may require medical or surgical intervention to prevent 1 of the outcomes listed above.
    Time Frame Up to 21 months

    Outcome Measure Data

    Analysis Population Description
    The safety population included all participants enrolled in the study who received at least 1 dose of epacadostat, pembrolizumab, or an applicable chemotherapy regimen.
    Arm/Group Title Group A: Epa + Pembrolizumab + mFOLFOX6 Group B: Epa + Pembrolizumab + Nab-Paclitaxel and Gemcitabine Group C: Epa + Pembrolizumab + Paclitaxel and Carboplatin Group D: Epa + Pembrolizumab + Pemetrexed and Platinum Agent Group E: Epa + Pembrolizumab + Cyclophosphamide Group F: Epa + Pembrolizumab + Gemcitabine and Platinum Agent Group G: Epa + Pembrolizumab + 5-FU and Platinum Agent
    Arm/Group Description Epacadostat (Epa) oral twice-daily (BID) continuous daily dosing at the protocol-defined dose in combination with pembrolizumab administered intravenously (IV) in combination with mFOLFOX6 (oxaliplatin IV + leucovorin IV + 5-fluorouracil (5-FU) IV. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with nab-paclitaxel IV and gemcitabine IV. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) in combination with paclitaxel IV and carboplatin IV. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with pemetrexed IV and Investigator's choice of platinum agent: carboplatin IV or cisplatin IV. Epa (100 mg)oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with cyclophosphamide PO. Epa oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab IV in combination with gemcitabine IV and Investigator's choice of platinum agent: carboplatin IV or cisplatin IV. Epa oral BID continuousdaily dosing at the protocol-defined dose in combination with pembrolizumab IV in combination with 5-FU IV and Investigator's choice of platinum agent: carboplatin IV or cisplatin IV.
    Measure Participants 9 9 11 9 13 8 11
    TEAE
    9
    100%
    9
    100%
    11
    100%
    9
    100%
    13
    100%
    8
    100%
    11
    100%
    Serious TEAE
    5
    55.6%
    5
    55.6%
    3
    27.3%
    6
    66.7%
    4
    30.8%
    6
    75%
    5
    45.5%
    2. Primary Outcome
    Title Phases 1 and 2: Number of Participants With Dose Limiting Toxicities (DLTs)
    Description A DLT was defined as the occurrence of any of the protocol-specified toxicities occurring up to and including Day 28 for the cohorts where mFOLFOX6 and nab-paclitaxel/gemcitabine are administered and Day 21 for all other chemotherapy regimens in Phase 1, except those with a clear alternative explanation (eg, disease progression) or transient (≤ 72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination.
    Time Frame 28 days

    Outcome Measure Data

    Analysis Population Description
    The safety population included all participants enrolled in the study who received at least 1 dose of epacadostat, pembrolizumab, or an applicable chemotherapy regimen.
    Arm/Group Title Group A: Epa + Pembrolizumab + mFOLFOX6 Group B: Epa + Pembrolizumab + Nab-Paclitaxel and Gemcitabine Group C: Epa + Pembrolizumab + Paclitaxel and Carboplatin Group D: Epa + Pembrolizumab + Pemetrexed and Platinum Agent Group E: Epa + Pembrolizumab + Cyclophosphamide Group F: Epa + Pembrolizumab + Gemcitabine and Platinum Agent Group G: Epa + Pembrolizumab + 5-FU and Platinum Agent
    Arm/Group Description Epacadostat (Epa) oral twice-daily (BID) continuous daily dosing at the protocol-defined dose in combination with pembrolizumab administered intravenously (IV) in combination with mFOLFOX6 (oxaliplatin IV + leucovorin IV + 5-fluorouracil (5-FU) IV. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with nab-paclitaxel IV and gemcitabine IV. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) in combination with paclitaxel IV and carboplatin IV. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with pemetrexed IV and Investigator's choice of platinum agent: carboplatin IV or cisplatin IV. Epa (100 mg)oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with cyclophosphamide PO. Epa oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab IV in combination with gemcitabine IV and Investigator's choice of platinum agent: carboplatin IV or cisplatin IV. Epa oral BID continuousdaily dosing at the protocol-defined dose in combination with pembrolizumab IV in combination with 5-FU IV and Investigator's choice of platinum agent: carboplatin IV or cisplatin IV.
    Measure Participants 9 9 11 9 13 8 11
    Count of Participants [Participants]
    2
    22.2%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    37.5%
    0
    0%
    3. Primary Outcome
    Title Phases 1 and 2: Objective Response Rate (ORR)
    Description ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
    Time Frame Up to Week 18

    Outcome Measure Data

    Analysis Population Description
    The full analysis set included all participants enrolled in the study who received at least 1 dose of epacadostat and have at least 1 postbaseline assessment or who discontinued epacadostat.
    Arm/Group Title Group A: Epa + Pembrolizumab + mFOLFOX6 Group B: Epa + Pembrolizumab + Nab-Paclitaxel and Gemcitabine Group C: Epa + Pembrolizumab + Paclitaxel and Carboplatin Group D: Epa + Pembrolizumab + Pemetrexed and Platinum Agent Group E: Epa + Pembrolizumab + Cyclophosphamide Group F: Epa + Pembrolizumab + Gemcitabine and Platinum Agent Group G: Epa + Pembrolizumab + 5-FU and Platinum Agent
    Arm/Group Description Epacadostat (Epa) oral twice-daily (BID) continuous daily dosing at the protocol-defined dose in combination with pembrolizumab administered intravenously (IV) in combination with mFOLFOX6 (oxaliplatin IV + leucovorin IV + 5-fluorouracil (5-FU) IV. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with nab-paclitaxel IV and gemcitabine IV. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) in combination with paclitaxel IV and carboplatin IV. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with pemetrexed IV and Investigator's choice of platinum agent: carboplatin IV or cisplatin IV. Epa (100 mg)oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with cyclophosphamide PO. Epa oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab IV in combination with gemcitabine IV and Investigator's choice of platinum agent: carboplatin IV or cisplatin IV. Epa oral BID continuousdaily dosing at the protocol-defined dose in combination with pembrolizumab IV in combination with 5-FU IV and Investigator's choice of platinum agent: carboplatin IV or cisplatin IV.
    Measure Participants 9 9 11 9 13 8 11
    Complete Response
    0
    0%
    1
    11.1%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Partial Response
    5
    55.6%
    2
    22.2%
    3
    27.3%
    2
    22.2%
    3
    23.1%
    1
    12.5%
    5
    45.5%

    Adverse Events

    Time Frame Up to 21 months
    Adverse Event Reporting Description The safety population included all participants enrolled in the study who received at least 1 dose of epacadostat, pembrolizumab, or an applicable chemotherapy regimen.
    Arm/Group Title Group A: Epa + Pembrolizumab + mFOLFOX6 Group B: Epa + Pembrolizumab + Nab-Paclitaxel and Gemcitabine Group C: Epa + Pembrolizumab + Paclitaxel and Carboplatin Group D: Epa + Pembrolizumab + Pemetrexed and Platinum Agent Group E: Epa + Pembrolizumab + Cyclophosphamide Group F: Epa + Pembrolizumab + Gemcitabine and Platinum Agent Group G: Epa + Pembrolizumab + 5-FU and Platinum Agent Total
    Arm/Group Description Epacadostat (Epa) oral twice-daily (BID) continuous daily dosing at the protocol-defined dose in combination with pembrolizumab administered intravenously (IV) in combination with mFOLFOX6 (oxaliplatin IV + leucovorin IV + 5-fluorouracil (5-FU) IV. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with nab-paclitaxel IV and gemcitabine IV. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) in combination with paclitaxel IV and carboplatin IV. Epa (100 mg) oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with pemetrexed IV and Investigator's choice of platinum agent: carboplatin IV or cisplatin IV. Epa (100 mg)oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab (200 mg) IV in combination with cyclophosphamide PO. Epa oral BID continuous daily dosing at the protocol-defined dose in combination with pembrolizumab IV in combination with gemcitabine IV and Investigator's choice of platinum agent: carboplatin IV or cisplatin IV. Epa oral BID continuousdaily dosing at the protocol-defined dose in combination with pembrolizumab IV in combination with 5-FU IV and Investigator's choice of platinum agent: carboplatin IV or cisplatin IV. Total
    All Cause Mortality
    Group A: Epa + Pembrolizumab + mFOLFOX6 Group B: Epa + Pembrolizumab + Nab-Paclitaxel and Gemcitabine Group C: Epa + Pembrolizumab + Paclitaxel and Carboplatin Group D: Epa + Pembrolizumab + Pemetrexed and Platinum Agent Group E: Epa + Pembrolizumab + Cyclophosphamide Group F: Epa + Pembrolizumab + Gemcitabine and Platinum Agent Group G: Epa + Pembrolizumab + 5-FU and Platinum Agent 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 Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/9 (66.7%) 6/9 (66.7%) 4/11 (36.4%) 1/9 (11.1%) 6/13 (46.2%) 2/8 (25%) 3/11 (27.3%) 28/70 (40%)
    Serious Adverse Events
    Group A: Epa + Pembrolizumab + mFOLFOX6 Group B: Epa + Pembrolizumab + Nab-Paclitaxel and Gemcitabine Group C: Epa + Pembrolizumab + Paclitaxel and Carboplatin Group D: Epa + Pembrolizumab + Pemetrexed and Platinum Agent Group E: Epa + Pembrolizumab + Cyclophosphamide Group F: Epa + Pembrolizumab + Gemcitabine and Platinum Agent Group G: Epa + Pembrolizumab + 5-FU and Platinum Agent 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 Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/9 (55.6%) 5/9 (55.6%) 5/11 (45.5%) 3/9 (33.3%) 6/13 (46.2%) 4/8 (50%) 6/11 (54.5%) 34/70 (48.6%)
    Blood and lymphatic system disorders
    Anaemia 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 2/70 (2.9%) 2
    Febrile neutropenia 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 2/70 (2.9%) 2
    Leukopenia 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Lymphopenia 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Neutropenia 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Pure white cell aplasia 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Thrombocytopenia 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Cardiac disorders
    Palpitations 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Gastrointestinal disorders
    Abdominal pain 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Diarrhoea 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 2/70 (2.9%) 2
    Dysphagia 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Gastrointestinal haemorrhage 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 2/70 (2.9%) 2
    Nausea 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 1/11 (9.1%) 1 3/70 (4.3%) 3
    Oesophagitis 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Rectal haemorrhage 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Small intestinal obstruction 1/9 (11.1%) 2 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 2
    Stomatitis 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Vomiting 0/9 (0%) 0 1/9 (11.1%) 1 1/11 (9.1%) 1 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 1/11 (9.1%) 1 4/70 (5.7%) 4
    General disorders
    Death 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 2/70 (2.9%) 2
    Disease progression 2/9 (22.2%) 2 0/9 (0%) 0 3/11 (27.3%) 3 1/9 (11.1%) 1 1/13 (7.7%) 1 1/8 (12.5%) 1 1/11 (9.1%) 1 9/70 (12.9%) 9
    Pyrexia 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 2/70 (2.9%) 2
    Hepatobiliary disorders
    Bile duct obstruction 0/9 (0%) 0 1/9 (11.1%) 2 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 2/70 (2.9%) 3
    Infections and infestations
    Catheter site cellulitis 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Cellulitis 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Influenza 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Large intestine infection 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Pneumonia 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 1/8 (12.5%) 1 0/11 (0%) 0 2/70 (2.9%) 2
    Urosepsis 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Injury, poisoning and procedural complications
    Lower limb fracture 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Investigations
    Ammonia increased 0/9 (0%) 0 1/9 (11.1%) 2 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 2
    Neutrophil count decreased 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Platelet count decreased 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    White blood cell count decreased 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Metabolism and nutrition disorders
    Dehydration 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Failure to thrive 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Hyperammonaemia 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Hyponatraemia 0/9 (0%) 0 0/9 (0%) 0 2/11 (18.2%) 2 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 3/70 (4.3%) 3
    Musculoskeletal and connective tissue disorders
    Intervertebral disc degeneration 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cervix cancer metastatic 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Malignant neoplasm progression 0/9 (0%) 0 2/9 (22.2%) 2 0/11 (0%) 0 0/9 (0%) 0 2/13 (15.4%) 2 0/8 (0%) 0 0/11 (0%) 0 4/70 (5.7%) 4
    Tumour pain 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 2/70 (2.9%) 2
    Nervous system disorders
    Cerebrovascular accident 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Seizure 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Spinal cord compression 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 1/11 (9.1%) 1 2/70 (2.9%) 2
    Syncope 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Renal and urinary disorders
    Acute kidney injury 1/9 (11.1%) 1 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 2/70 (2.9%) 2
    Urinary tract obstruction 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Reproductive system and breast disorders
    Vaginal haemorrhage 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 2/70 (2.9%) 2
    Respiratory, thoracic and mediastinal disorders
    Cough 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Dyspnoea 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 1/11 (9.1%) 1 2/70 (2.9%) 2
    Pulmonary embolism 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Vascular disorders
    Hypotension 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Orthostatic hypotension 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Other (Not Including Serious) Adverse Events
    Group A: Epa + Pembrolizumab + mFOLFOX6 Group B: Epa + Pembrolizumab + Nab-Paclitaxel and Gemcitabine Group C: Epa + Pembrolizumab + Paclitaxel and Carboplatin Group D: Epa + Pembrolizumab + Pemetrexed and Platinum Agent Group E: Epa + Pembrolizumab + Cyclophosphamide Group F: Epa + Pembrolizumab + Gemcitabine and Platinum Agent Group G: Epa + Pembrolizumab + 5-FU and Platinum Agent 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 Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/9 (100%) 8/9 (88.9%) 11/11 (100%) 9/9 (100%) 13/13 (100%) 8/8 (100%) 10/11 (90.9%) 68/70 (97.1%)
    Blood and lymphatic system disorders
    Anaemia 2/9 (22.2%) 2 5/9 (55.6%) 6 4/11 (36.4%) 5 3/9 (33.3%) 4 6/13 (46.2%) 9 4/8 (50%) 4 3/11 (27.3%) 3 27/70 (38.6%) 33
    Increased tendency to bruise 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Leukocytosis 1/9 (11.1%) 1 3/9 (33.3%) 3 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 2/8 (25%) 2 1/11 (9.1%) 1 8/70 (11.4%) 8
    Leukopenia 1/9 (11.1%) 2 1/9 (11.1%) 3 3/11 (27.3%) 3 2/9 (22.2%) 2 1/13 (7.7%) 1 4/8 (50%) 8 1/11 (9.1%) 1 13/70 (18.6%) 20
    Lymph node pain 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Lymphadenopathy 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 1/9 (11.1%) 1 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 3/70 (4.3%) 3
    Lymphopenia 0/9 (0%) 0 2/9 (22.2%) 3 1/11 (9.1%) 1 1/9 (11.1%) 1 4/13 (30.8%) 4 2/8 (25%) 2 1/11 (9.1%) 1 11/70 (15.7%) 12
    Neutropenia 2/9 (22.2%) 7 5/9 (55.6%) 13 5/11 (45.5%) 5 2/9 (22.2%) 2 2/13 (15.4%) 5 5/8 (62.5%) 9 3/11 (27.3%) 3 24/70 (34.3%) 44
    Thrombocytopenia 1/9 (11.1%) 1 7/9 (77.8%) 16 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 4/8 (50%) 5 2/11 (18.2%) 3 15/70 (21.4%) 26
    Cardiac disorders
    Palpitations 1/9 (11.1%) 1 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 3/70 (4.3%) 3
    Sinus tachycardia 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Ear and labyrinth disorders
    Ear pain 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Vertigo 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Endocrine disorders
    Adrenal insufficiency 0/9 (0%) 0 0/9 (0%) 0 2/11 (18.2%) 2 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 2/70 (2.9%) 2
    Autoimmune thyroiditis 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Hyperthyroidism 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Hypothyroidism 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 2/70 (2.9%) 2
    Steroid withdrawal syndrome 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Thyroiditis 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Eye disorders
    Abnormal sensation in eye 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Blindness transient 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Cataract 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Diplopia 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Dry eye 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 3/9 (33.3%) 3 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 3/70 (4.3%) 3
    Eczema eyelids 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Eye inflammation 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Eye pain 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Lacrimation increased 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 1/9 (11.1%) 1 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 3/70 (4.3%) 3
    Periorbital oedema 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Photophobia 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Vision blurred 0/9 (0%) 0 0/9 (0%) 0 3/11 (27.3%) 3 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 3/70 (4.3%) 3
    Gastrointestinal disorders
    Abdominal discomfort 0/9 (0%) 0 1/9 (11.1%) 16 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 16
    Abdominal distension 0/9 (0%) 0 2/9 (22.2%) 2 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 1/8 (12.5%) 1 0/11 (0%) 0 4/70 (5.7%) 4
    Abdominal hernia 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Abdominal pain 1/9 (11.1%) 1 1/9 (11.1%) 1 2/11 (18.2%) 3 0/9 (0%) 0 1/13 (7.7%) 1 2/8 (25%) 2 1/11 (9.1%) 1 8/70 (11.4%) 9
    Abdominal pain lower 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Abdominal pain upper 1/9 (11.1%) 2 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 1/11 (9.1%) 1 3/70 (4.3%) 4
    Anal fissure 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Anal incontinence 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Anorectal swelling 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Aphthous ulcer 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Ascites 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Cheilitis 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Constipation 3/9 (33.3%) 3 1/9 (11.1%) 2 3/11 (27.3%) 4 3/9 (33.3%) 3 1/13 (7.7%) 1 2/8 (25%) 2 0/11 (0%) 0 13/70 (18.6%) 15
    Defaecation urgency 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Dental caries 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Diarrhoea 3/9 (33.3%) 6 5/9 (55.6%) 6 6/11 (54.5%) 6 4/9 (44.4%) 4 4/13 (30.8%) 5 0/8 (0%) 0 4/11 (36.4%) 5 26/70 (37.1%) 32
    Dyspepsia 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 2/70 (2.9%) 2
    Dysphagia 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 3/11 (27.3%) 5 5/70 (7.1%) 7
    Epigastric discomfort 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Eructation 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 2/70 (2.9%) 2
    Faeces soft 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Flatulence 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 2/70 (2.9%) 2
    Frequent bowel movements 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Gastritis 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 2/9 (22.2%) 2 0/13 (0%) 0 1/8 (12.5%) 1 1/11 (9.1%) 1 5/70 (7.1%) 5
    Gastrooesophageal reflux disease 0/9 (0%) 0 1/9 (11.1%) 1 1/11 (9.1%) 1 1/9 (11.1%) 1 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 4/70 (5.7%) 4
    Gingival bleeding 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Haematochezia 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Haemorrhoids 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 2/70 (2.9%) 2
    Hypoaesthesia oral 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Hypoaesthesia teeth 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Mouth ulceration 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 1/8 (12.5%) 1 1/11 (9.1%) 1 3/70 (4.3%) 3
    Nausea 2/9 (22.2%) 3 5/9 (55.6%) 5 8/11 (72.7%) 13 7/9 (77.8%) 7 4/13 (30.8%) 5 4/8 (50%) 4 7/11 (63.6%) 7 37/70 (52.9%) 44
    Oesophageal spasm 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Oesophagitis 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Salivary hypersecretion 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Stomatitis 3/9 (33.3%) 3 3/9 (33.3%) 4 2/11 (18.2%) 2 2/9 (22.2%) 3 1/13 (7.7%) 1 0/8 (0%) 0 5/11 (45.5%) 7 16/70 (22.9%) 20
    Toothache 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Vomiting 0/9 (0%) 0 3/9 (33.3%) 3 5/11 (45.5%) 5 3/9 (33.3%) 3 3/13 (23.1%) 4 3/8 (37.5%) 3 3/11 (27.3%) 3 20/70 (28.6%) 21
    General disorders
    Asthenia 1/9 (11.1%) 1 2/9 (22.2%) 2 1/11 (9.1%) 1 1/9 (11.1%) 1 1/13 (7.7%) 1 1/8 (12.5%) 1 0/11 (0%) 0 7/70 (10%) 7
    Axillary pain 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Catheter site pain 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Chest discomfort 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Chills 0/9 (0%) 0 0/9 (0%) 0 4/11 (36.4%) 4 2/9 (22.2%) 2 3/13 (23.1%) 4 0/8 (0%) 0 0/11 (0%) 0 9/70 (12.9%) 10
    Facial pain 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Fatigue 7/9 (77.8%) 9 5/9 (55.6%) 7 6/11 (54.5%) 7 7/9 (77.8%) 7 6/13 (46.2%) 6 4/8 (50%) 4 4/11 (36.4%) 4 39/70 (55.7%) 44
    Gait disturbance 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Generalised oedema 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Influenza like illness 1/9 (11.1%) 1 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 3/70 (4.3%) 3
    Malaise 1/9 (11.1%) 2 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 2/70 (2.9%) 3
    Non-cardiac chest pain 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 2/13 (15.4%) 3 0/8 (0%) 0 0/11 (0%) 0 3/70 (4.3%) 4
    Oedema 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Oedema peripheral 1/9 (11.1%) 1 2/9 (22.2%) 2 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 1/11 (9.1%) 1 5/70 (7.1%) 5
    Pain 0/9 (0%) 0 1/9 (11.1%) 1 1/11 (9.1%) 1 1/9 (11.1%) 1 1/13 (7.7%) 2 0/8 (0%) 0 0/11 (0%) 0 4/70 (5.7%) 5
    Pyrexia 2/9 (22.2%) 2 1/9 (11.1%) 1 0/11 (0%) 0 1/9 (11.1%) 1 2/13 (15.4%) 2 0/8 (0%) 0 0/11 (0%) 0 6/70 (8.6%) 6
    Temperature intolerance 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Immune system disorders
    Drug hypersensitivity 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Seasonal allergy 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Infections and infestations
    Bacteroides bacteraemia 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Body tinea 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Bronchitis 0/9 (0%) 0 3/9 (33.3%) 3 1/11 (9.1%) 1 2/9 (22.2%) 2 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 7/70 (10%) 7
    Candida infection 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Cellulitis 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 2/11 (18.2%) 2 3/70 (4.3%) 3
    Clostridium bacteraemia 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Clostridium difficile colitis 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Conjunctivitis 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 2/70 (2.9%) 2
    Ear infection 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Escherichia infection 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Folliculitis 0/9 (0%) 0 2/9 (22.2%) 2 2/11 (18.2%) 2 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 5/70 (7.1%) 5
    Fungal skin infection 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Gingivitis 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Herpes virus infection 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Herpes zoster 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Hordeolum 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 2/70 (2.9%) 2
    Nasopharyngitis 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 2/70 (2.9%) 2
    Oral candidiasis 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Pneumonia 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Pyuria 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Rash pustular 0/9 (0%) 0 0/9 (0%) 0 2/11 (18.2%) 2 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 2/70 (2.9%) 2
    Respiratory tract infection 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Sinusitis 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 3 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 2/70 (2.9%) 4
    Staphylococcal infection 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Stoma site infection 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Tinea cruris 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Upper respiratory tract infection 0/9 (0%) 0 0/9 (0%) 0 2/11 (18.2%) 2 1/9 (11.1%) 1 0/13 (0%) 0 2/8 (25%) 3 0/11 (0%) 0 5/70 (7.1%) 6
    Urinary tract infection 1/9 (11.1%) 1 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 2/13 (15.4%) 2 0/8 (0%) 0 2/11 (18.2%) 2 6/70 (8.6%) 6
    Vulvovaginitis 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Injury, poisoning and procedural complications
    Contusion 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Incision site pain 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Infusion related reaction 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 2/8 (25%) 2 0/11 (0%) 0 3/70 (4.3%) 3
    Skin abrasion 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Stoma site haemorrhage 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Stoma site inflammation 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Stoma site irritation 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Stoma site pain 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 2/70 (2.9%) 2
    Tooth fracture 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Investigations
    Activated partial thromboplastin time prolonged 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Alanine aminotransferase increased 3/9 (33.3%) 3 3/9 (33.3%) 3 3/11 (27.3%) 3 3/9 (33.3%) 3 1/13 (7.7%) 1 2/8 (25%) 3 1/11 (9.1%) 1 16/70 (22.9%) 17
    Amylase increased 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 3/70 (4.3%) 3
    Aspartate aminotransferase increased 3/9 (33.3%) 3 3/9 (33.3%) 4 3/11 (27.3%) 4 3/9 (33.3%) 3 1/13 (7.7%) 1 1/8 (12.5%) 1 0/11 (0%) 0 14/70 (20%) 16
    Blood alkaline phosphatase increased 2/9 (22.2%) 2 3/9 (33.3%) 3 3/11 (27.3%) 3 1/9 (11.1%) 1 2/13 (15.4%) 2 2/8 (25%) 2 0/11 (0%) 0 13/70 (18.6%) 13
    Blood bilirubin increased 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Blood creatinine increased 0/9 (0%) 0 0/9 (0%) 0 3/11 (27.3%) 5 1/9 (11.1%) 1 0/13 (0%) 0 1/8 (12.5%) 1 1/11 (9.1%) 1 6/70 (8.6%) 8
    Blood lactate dehydrogenase increased 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 2 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 2
    Blood pressure increased 1/9 (11.1%) 1 1/9 (11.1%) 1 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 4/70 (5.7%) 4
    Lipase increased 2/9 (22.2%) 2 0/9 (0%) 0 2/11 (18.2%) 2 1/9 (11.1%) 1 1/13 (7.7%) 1 0/8 (0%) 0 1/11 (9.1%) 1 7/70 (10%) 7
    Lymphocyte count decreased 0/9 (0%) 0 0/9 (0%) 0 2/11 (18.2%) 2 1/9 (11.1%) 1 2/13 (15.4%) 2 0/8 (0%) 0 0/11 (0%) 0 5/70 (7.1%) 5
    Neutrophil count decreased 1/9 (11.1%) 2 1/9 (11.1%) 1 3/11 (27.3%) 6 0/9 (0%) 0 1/13 (7.7%) 2 1/8 (12.5%) 1 1/11 (9.1%) 1 8/70 (11.4%) 13
    Neutrophil toxic granulation present 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Platelet count decreased 1/9 (11.1%) 1 1/9 (11.1%) 1 2/11 (18.2%) 5 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 2 0/11 (0%) 0 5/70 (7.1%) 9
    Shift to the left 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Transaminases increased 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Weight decreased 0/9 (0%) 0 2/9 (22.2%) 2 1/11 (9.1%) 1 0/9 (0%) 0 2/13 (15.4%) 2 1/8 (12.5%) 1 0/11 (0%) 0 6/70 (8.6%) 6
    Weight increased 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    White blood cell count decreased 1/9 (11.1%) 2 1/9 (11.1%) 1 3/11 (27.3%) 7 2/9 (22.2%) 2 1/13 (7.7%) 3 1/8 (12.5%) 1 0/11 (0%) 0 9/70 (12.9%) 16
    Metabolism and nutrition disorders
    Decreased appetite 2/9 (22.2%) 2 2/9 (22.2%) 2 3/11 (27.3%) 3 1/9 (11.1%) 2 1/13 (7.7%) 1 0/8 (0%) 0 3/11 (27.3%) 3 12/70 (17.1%) 13
    Dehydration 3/9 (33.3%) 3 2/9 (22.2%) 3 1/11 (9.1%) 2 1/9 (11.1%) 1 1/13 (7.7%) 1 1/8 (12.5%) 1 4/11 (36.4%) 4 13/70 (18.6%) 15
    Fluid retention 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Hypercalcaemia 0/9 (0%) 0 0/9 (0%) 0 3/11 (27.3%) 3 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 3/70 (4.3%) 3
    Hyperglycaemia 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Hyperkalaemia 0/9 (0%) 0 1/9 (11.1%) 1 1/11 (9.1%) 1 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 3/70 (4.3%) 3
    Hypertriglyceridaemia 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Hyperuricaemia 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 2 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 2
    Hypoalbuminaemia 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 2/13 (15.4%) 2 0/8 (0%) 0 0/11 (0%) 0 3/70 (4.3%) 3
    Hypocalcaemia 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Hypokalaemia 1/9 (11.1%) 1 1/9 (11.1%) 1 2/11 (18.2%) 3 3/9 (33.3%) 4 2/13 (15.4%) 3 0/8 (0%) 0 1/11 (9.1%) 1 10/70 (14.3%) 13
    Hypomagnesaemia 1/9 (11.1%) 1 1/9 (11.1%) 1 3/11 (27.3%) 8 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 7/70 (10%) 12
    Hyponatraemia 1/9 (11.1%) 1 1/9 (11.1%) 1 1/11 (9.1%) 1 0/9 (0%) 0 1/13 (7.7%) 2 0/8 (0%) 0 0/11 (0%) 0 4/70 (5.7%) 5
    Hypophosphataemia 0/9 (0%) 0 0/9 (0%) 0 2/11 (18.2%) 2 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 3/70 (4.3%) 3
    Hypovolaemia 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Iron overload 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Lactic acidosis 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Vitamin D deficiency 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/9 (11.1%) 1 0/9 (0%) 0 3/11 (27.3%) 3 0/9 (0%) 0 1/13 (7.7%) 1 1/8 (12.5%) 1 1/11 (9.1%) 2 7/70 (10%) 8
    Back pain 1/9 (11.1%) 1 0/9 (0%) 0 3/11 (27.3%) 3 0/9 (0%) 0 1/13 (7.7%) 1 1/8 (12.5%) 1 0/11 (0%) 0 6/70 (8.6%) 6
    Bone pain 1/9 (11.1%) 1 3/9 (33.3%) 3 4/11 (36.4%) 5 1/9 (11.1%) 1 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 10/70 (14.3%) 11
    Chest wall mass 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Flank pain 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Muscle spasms 2/9 (22.2%) 2 1/9 (11.1%) 1 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 4/70 (5.7%) 4
    Muscle tightness 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Muscular weakness 1/9 (11.1%) 1 1/9 (11.1%) 1 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 3/70 (4.3%) 3
    Musculoskeletal chest pain 1/9 (11.1%) 1 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 2 1/11 (9.1%) 1 4/70 (5.7%) 5
    Musculoskeletal pain 1/9 (11.1%) 1 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 2/13 (15.4%) 2 0/8 (0%) 0 0/11 (0%) 0 4/70 (5.7%) 4
    Myalgia 0/9 (0%) 0 2/9 (22.2%) 2 2/11 (18.2%) 2 1/9 (11.1%) 1 1/13 (7.7%) 1 1/8 (12.5%) 1 0/11 (0%) 0 7/70 (10%) 7
    Neck pain 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Osteoarthritis 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Pain in extremity 0/9 (0%) 0 2/9 (22.2%) 2 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 3/70 (4.3%) 3
    Pain in jaw 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasm progression 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Tumour flare 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Tumour haemorrhage 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Tumour inflammation 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Tumour pain 2/9 (22.2%) 2 2/9 (22.2%) 2 2/11 (18.2%) 3 2/9 (22.2%) 2 1/13 (7.7%) 1 1/8 (12.5%) 1 2/11 (18.2%) 2 12/70 (17.1%) 13
    Nervous system disorders
    Ageusia 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Amnesia 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Aphasia 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Dizziness 1/9 (11.1%) 1 1/9 (11.1%) 1 3/11 (27.3%) 3 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 2/11 (18.2%) 2 7/70 (10%) 7
    Dysaesthesia 2/9 (22.2%) 2 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 3/70 (4.3%) 3
    Dysgeusia 3/9 (33.3%) 3 1/9 (11.1%) 2 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 1/8 (12.5%) 1 2/11 (18.2%) 2 8/70 (11.4%) 9
    Head titubation 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Headache 1/9 (11.1%) 1 1/9 (11.1%) 1 4/11 (36.4%) 4 1/9 (11.1%) 1 0/13 (0%) 0 2/8 (25%) 2 0/11 (0%) 0 9/70 (12.9%) 9
    Hemiparesis 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Hypoaesthesia 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Hypogeusia 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Memory impairment 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Migraine 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Neuropathy peripheral 7/9 (77.8%) 8 3/9 (33.3%) 4 5/11 (45.5%) 5 3/9 (33.3%) 3 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 19/70 (27.1%) 21
    Peripheral sensory neuropathy 0/9 (0%) 0 1/9 (11.1%) 1 5/11 (45.5%) 5 1/9 (11.1%) 1 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 8/70 (11.4%) 8
    Restless legs syndrome 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Taste disorder 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Tremor 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Product Issues
    Stent malfunction 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Psychiatric disorders
    Anxiety 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 2/70 (2.9%) 2
    Depression 0/9 (0%) 0 1/9 (11.1%) 1 2/11 (18.2%) 2 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 4/70 (5.7%) 4
    Insomnia 2/9 (22.2%) 2 1/9 (11.1%) 1 2/11 (18.2%) 2 3/9 (33.3%) 3 2/13 (15.4%) 2 0/8 (0%) 0 0/11 (0%) 0 10/70 (14.3%) 10
    Irritability 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Mental status changes 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Renal and urinary disorders
    Haematuria 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Hydronephrosis 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Pollakiuria 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 3/70 (4.3%) 3
    Renal salt-wasting syndrome 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Stress urinary incontinence 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Urinary incontinence 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Reproductive system and breast disorders
    Testicular pain 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Vaginal haemorrhage 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Vaginal ulceration 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Respiratory, thoracic and mediastinal disorders
    Cough 2/9 (22.2%) 2 2/9 (22.2%) 3 2/11 (18.2%) 2 1/9 (11.1%) 1 1/13 (7.7%) 1 0/8 (0%) 0 2/11 (18.2%) 2 10/70 (14.3%) 11
    Dysphonia 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 2/70 (2.9%) 2
    Dyspnoea 1/9 (11.1%) 1 0/9 (0%) 0 2/11 (18.2%) 3 1/9 (11.1%) 1 0/13 (0%) 0 3/8 (37.5%) 3 0/11 (0%) 0 7/70 (10%) 8
    Dyspnoea exertional 1/9 (11.1%) 1 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 3/70 (4.3%) 3
    Epistaxis 0/9 (0%) 0 2/9 (22.2%) 2 1/11 (9.1%) 1 2/9 (22.2%) 2 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 6/70 (8.6%) 6
    Haemoptysis 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 2/70 (2.9%) 2
    Hiccups 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Hypoxia 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Nasal congestion 1/9 (11.1%) 1 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 3/70 (4.3%) 3
    Nasal discomfort 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Oropharyngeal pain 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 2/70 (2.9%) 2
    Painful respiration 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Pharyngeal inflammation 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Pneumonitis 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Pneumothorax 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Productive cough 0/9 (0%) 0 1/9 (11.1%) 2 0/11 (0%) 0 2/9 (22.2%) 2 0/13 (0%) 0 1/8 (12.5%) 1 1/11 (9.1%) 1 5/70 (7.1%) 6
    Pulmonary embolism 0/9 (0%) 0 0/9 (0%) 0 2/11 (18.2%) 2 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 2/70 (2.9%) 2
    Pulmonary fibrosis 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Rhinitis allergic 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Wheezing 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 3/70 (4.3%) 3
    Skin and subcutaneous tissue disorders
    Alopecia 1/9 (11.1%) 1 2/9 (22.2%) 2 5/11 (45.5%) 5 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 9/70 (12.9%) 9
    Blister 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Decubitus ulcer 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Dermatitis bullous 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Dermatitis contact 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Dermatitis exfoliative 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Dermatitis psoriasiform 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Dry skin 1/9 (11.1%) 1 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 2/70 (2.9%) 2
    Erythema 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Hyperhidrosis 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Night sweats 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 2/9 (22.2%) 2 1/13 (7.7%) 1 0/8 (0%) 0 1/11 (9.1%) 1 4/70 (5.7%) 4
    Palmar erythema 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Palmar-plantar erythrodysaesthesia syndrome 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 2/70 (2.9%) 2
    Petechiae 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Pruritus 1/9 (11.1%) 1 1/9 (11.1%) 1 1/11 (9.1%) 1 3/9 (33.3%) 3 1/13 (7.7%) 1 2/8 (25%) 2 1/11 (9.1%) 2 10/70 (14.3%) 11
    Rash 1/9 (11.1%) 2 4/9 (44.4%) 5 3/11 (27.3%) 3 0/9 (0%) 0 1/13 (7.7%) 1 2/8 (25%) 2 3/11 (27.3%) 4 14/70 (20%) 17
    Rash erythematous 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Rash maculo-papular 1/9 (11.1%) 1 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 3/70 (4.3%) 3
    Rash pruritic 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 2/13 (15.4%) 2 0/8 (0%) 0 1/11 (9.1%) 1 3/70 (4.3%) 3
    Skin exfoliation 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/70 (1.4%) 1
    Vascular disorders
    Capillary leak syndrome 0/9 (0%) 0 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 1/70 (1.4%) 1
    Flushing 1/9 (11.1%) 2 0/9 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 3/70 (4.3%) 4
    Hot flush 2/9 (22.2%) 2 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 2/70 (2.9%) 2
    Hypertension 2/9 (22.2%) 2 0/9 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 2/70 (2.9%) 2
    Hypotension 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 1/13 (7.7%) 1 0/8 (0%) 0 0/11 (0%) 0 2/70 (2.9%) 2
    Thrombophlebitis superficial 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Thrombosis 0/9 (0%) 0 1/9 (11.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1
    Vascular pain 0/9 (0%) 0 0/9 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/13 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/70 (1.4%) 1

    Limitations/Caveats

    Enrollment in this study was permanently discontinued on 25 Oct 2018 due to a strategic decision and not based on safety concerns.

    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
    Email medinfo@incyte.com
    Responsible Party:
    Incyte Corporation
    ClinicalTrials.gov Identifier:
    NCT03085914
    Other Study ID Numbers:
    • INCB 24360-207 / ECHO-207
    • 2016-004678-16
    First Posted:
    Mar 21, 2017
    Last Update Posted:
    Aug 5, 2021
    Last Verified:
    Jul 1, 2021