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A Study of INCAGN01876 in Participants With Advanced or Metastatic Solid Tumors

Sponsor
Incyte Biosciences International Sàrl (Industry)
Overall Status
Completed
CT.gov ID
NCT02697591
Collaborator
(none)
100
Enrollment
8
Locations
10
Arms
41.9
Actual Duration (Months)
12.5
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This was an open-label, non-randomized Phase 1/2 safety study of INCAGN01876 in participants with advanced or metastatic solid tumors that was conducted in 2 parts. Part 1 is dose escalation and safety expansion which determines the optimal dose and maximum number of tolerated doses. Part 2 is dose expansion in which Part 1 recommended dose will be evaluated.

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

Study Design

Study Type:
Interventional
Actual Enrollment :
100 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCAGN01876 in Subjects With Advanced or Metastatic Solid Tumors
Actual Study Start Date :
Jun 20, 2016
Actual Primary Completion Date :
Dec 16, 2019
Actual Study Completion Date :
Dec 16, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Phase 1: 20.0 Milligram Per Kilograms (mg/kg) Every 2 Weeks (Q2W)

Participants received IV infusion of study drug at a dose of 20.0 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Drug: INCAGN01876
Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.
Experimental: Phase 1: 0.03 mg/kg Q2W

Participants received intravenous (IV) infusion of study drug at a dose of 0.03 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Drug: INCAGN01876
Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.
Experimental: Phase 1: 0.1 mg/kg Q2W

Participants received IV infusion of study drug at a dose of 0.1 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Drug: INCAGN01876
Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.
Experimental: Phase 1: 0.3 mg/kg Q2W

Participants received IV infusion of study drug at a dose of 0.3 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Drug: INCAGN01876
Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.
Experimental: Phase 1: 1.0 mg/kg Q2W

Participants received IV infusion of study drug at a dose of 1.0 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Drug: INCAGN01876
Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.
Experimental: Phase 1: 3.0 mg/kg Q2W

Participants received IV infusion of study drug at a dose of 3.0 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Drug: INCAGN01876
Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.
Experimental: Phase 1: 5.0 mg/kg Q2W

Participants received IV infusion of study drug at a dose of 5.0 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Drug: INCAGN01876
Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.
Experimental: Phase 1: 10.0 mg/kg Q2W

Participants received IV infusion of study drug at a dose of 10.0 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Drug: INCAGN01876
Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.
Experimental: Phase 1: 400 mg/kg Every 4 Weeks (Q4W)

Participants received IV infusion of study drug at a dose of 400 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Drug: INCAGN01876
Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.
Experimental: Phase 2: 300 mg/kg Q2W

Participants received IV infusion of study drug at a dose of 300 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Drug: INCAGN01876
Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity [From screening through 60 days after end of treatment, up to Month 15]

    AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A treatment-emergent AE is any AE either reported for first time or worsening of a pre-existing event after the first dose of study drug. Grade 1 AEs is defined as Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 AEs is defined as Moderate; minimal, local, or non-invasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3 AEs is defined as the severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living and Grade 4 AEs as life-threatening consequences; urgent intervention indicated. Data is reported for Grade 3 and higher severity for this outcome measure.

Secondary Outcome Measures

  1. Maximum Observed Plasma Concentration (Cmax) [Day 1 of Cycles 1 and 6 post-dose]

  2. Time to Maximum Concentration (Tmax) [Day 1 of Cycles 1 and 6 post-dose]

  3. Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) [Day 1 of Cycles 2, 3, 4, 6, and 7 post-dose]

  4. Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t) [Day 1 of Cycles 1 and 6 post-dose]

  5. Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) [Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months]

    ORR is defined as the percentage of participants having complete response (CR) or partial response (PR), as determined by investigator assessment of radiographic disease assessments. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.

  6. Duration of Response (DOR) Per RECIST and mRECIST [Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months]

    DOR is defined as the time from earliest date of disease response (CR or PR) until earliest date of disease progression, as determined by investigator assessment of radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.

  7. Duration of Disease Control Per RECIST and mRECIST [Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months]

    Duration of disease control (CR, PR, and stable disease [SD]), as measured from first report of SD or better until disease progression, as determined by investigator assessment of radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

  8. Progression Free Survival (PFS) Per RECIST and mRECIST [Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months]

    PFS is defined as the time from date of first dose of study drug until the earliest date of disease progression, as determined by investigator assessment of objective radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. Progression is defined by RECIST and mRECIST as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and an absolute lesion increase of at least 5 mm or the appearance of new lesions.

Eligibility Criteria

Criteria

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

  • Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.

  • Part 1: Participants with advanced or metastatic solid tumors.

  • Part 2: Participants with advanced or metastatic adenocarcinoma of endometrium, melanoma, non-small cell lung cancer, and renal cell carcinoma.

  • Participants who have disease progression after treatment with available therapies that are known to confer clinical benefit, or who are intolerant to treatment, or participants who refuse standard treatment.

  • Presence of measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

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

Exclusion Criteria:

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

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

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

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

  • Active autoimmune disease.

  • Prior treatment with any tumor necrosis factor super family agonist.

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

  • Evidence of active, non-infectious pneumonitis or history of interstitial lung disease.

  • Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.

Contacts and Locations

Locations

Site City State Country Postal Code
1 The Angeles Clinic and Research Institute Los Angeles California United States 90025
2 Yale University New Haven Connecticut United States 06511
3 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
4 Dana Farber Cancer Institute Boston Massachusetts United States 02215
5 Memorial Sloan Kettering at Monmouth Middletown New Jersey United States 07748
6 MSK Westchester Harrison New York United States 10604
7 Memorial Sloan Kettering Cancer Center New York New York United States 10065
8 Vanderbilt University Medical Center Nashville Tennessee United States 37232

Sponsors and Collaborators

  • Incyte Biosciences International Sàrl

Investigators

  • Study Director: John Janik, MD, Incyte Corporation

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Incyte Biosciences International Sàrl
ClinicalTrials.gov Identifier:
NCT02697591
Other Study ID Numbers:
  • INCAGN 1876-101
First Posted:
Mar 3, 2016
Last Update Posted:
Feb 26, 2021
Last Verified:
Feb 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by Incyte Biosciences International Sàrl
Solid tumor
adenocarcinoma of the endometrium
melanoma, non-small cell lung cancer (NSCLC)
renal cell carcinoma (RCC)
glucocorticoid-induced tumor necrosis factor receptor (GITR)
Additional relevant MeSH terms:
Neoplasm Metastasis

Study Results

Participant Flow

Recruitment Details A total of 100 participants were enrolled at 7 study sites in the United States from 20 June 2016 to 16 December 2019.
Pre-assignment Detail
Arm/Group Title Phase 1: 0.03 mg/kg Q2W Phase 1: 0.1 mg/kg Q2W Phase 1: 0.3 mg/kg Q2W Phase 1: 1.0 mg/kg Q2W Phase 1: 3.0 mg/kg Q2W Phase 1: 5.0 mg/kg Q2W Phase 1: 10.0 mg/kg Q2W Phase 1: 20.0 mg/kg Q2W Phase 1: 400 mg Q4W Phase 2: 300 mg Q2W
Arm/Group Description Participants received intravenous (IV) infusion of study drug at a dose of 0.03 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.1 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.3 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 1.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 3.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 5.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 10.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 20.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 400 mg Q4W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 300 mg Q2W starting on Day 1 of each cycle for up to 15 months.
Period Title: Overall Study
STARTED 4 4 4 3 15 18 16 4 10 22
COMPLETED 0 0 1 0 2 2 0 1 1 2
NOT COMPLETED 4 4 3 3 13 16 16 3 9 20

Baseline Characteristics

Arm/Group Title Phase 1: 0.03 mg/kg Q2W Phase 1: 0.1 mg/kg Q2W Phase 1: 0.3 mg/kg Q2W Phase 1: 1.0 mg/kg Q2W Phase 1: 3.0 mg/kg Q2W Phase 1: 5.0 mg/kg Q2W Phase 1: 10.0 mg/kg Q2W Phase 1: 20.0 mg/kg Q2W Phase 1: 400 mg Q4W Phase 2: 300 mg Q2W Total
Arm/Group Description INCAGN01876 was administered at 0.03mg/kg Q2W as part of dose escalation. INCAGN01876 was administered at 0.1mg/kg Q2W as part of dose escalation. INCAGN01876 was administered at 0.3mg/kg Q2W as part of dose escalation. INCAGN01876 was administered at 1.0mg/kg Q2W as part of dose escalation. INCAGN01876 was administered at 3mg/kg Q2W as part of dose escalation. INCAGN01876 was administered at 5mg/kg Q2W as part of dose escalation. INCAGN01876 was administered at 10mg/kg Q2W as part of dose escalation. INCAGN01876 was administered at 20mg/kg Q2W as part of dose escalation. INCAGN01876 was administered at 400mg Q4W as part of dose escalation. INCAGN01876 was administered at 300mg Q2W as part of dose escalation. Total of all reporting groups
Overall Participants 4 4 4 3 15 18 16 4 10 22 100
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
50.5
(17.02)
45.3
(21.01)
70.0
(12.19)
53.0
(14.93)
62.3
(10.58)
53.6
(12.83)
62.3
(10.22)
59.5
(14.75)
57.6
(12.02)
67.2
(10.86)
60.1
(13.23)
Sex: Female, Male (Count of Participants)
Female
2
50%
3
75%
2
50%
0
0%
8
53.3%
7
38.9%
5
31.3%
1
25%
4
40%
10
45.5%
42
42%
Male
2
50%
1
25%
2
50%
3
100%
7
46.7%
11
61.1%
11
68.8%
3
75%
6
60%
12
54.5%
58
58%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino
0
0%
0
0%
0
0%
0
0%
1
6.7%
1
5.6%
0
0%
0
0%
1
10%
2
9.1%
5
5%
Not Hispanic or Latino
4
100%
4
100%
4
100%
3
100%
14
93.3%
16
88.9%
15
93.8%
4
100%
9
90%
19
86.4%
92
92%
Not Reported
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
6.3%
0
0%
0
0%
1
4.5%
2
2%
Unknown
0
0%
0
0%
0
0%
0
0%
0
0%
1
5.6%
0
0%
0
0%
0
0%
0
0%
1
1%
Race/Ethnicity, Customized (Count of Participants)
White/Caucasian
3
75%
3
75%
2
50%
2
66.7%
13
86.7%
15
83.3%
12
75%
4
100%
7
70%
21
95.5%
82
82%
Black/African-American
1
25%
1
25%
1
25%
0
0%
2
13.3%
1
5.6%
2
12.5%
0
0%
0
0%
1
4.5%
9
9%
Asian
0
0%
0
0%
1
25%
0
0%
0
0%
0
0%
2
12.5%
0
0%
2
20%
0
0%
5
5%
Missing
0
0%
0
0%
0
0%
1
33.3%
0
0%
2
11.1%
0
0%
0
0%
1
10%
0
0%
4
4%
ECOG Performance Status (Count of Participants)
0
3
75%
1
25%
3
75%
2
66.7%
8
53.3%
10
55.6%
8
50%
1
25%
6
60%
12
54.5%
54
54%
1
1
25%
3
75%
1
25%
1
33.3%
7
46.7%
8
44.4%
8
50%
3
75%
4
40%
10
45.5%
46
46%
2
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
3
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
4
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
5
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%

Outcome Measures

1. Primary Outcome
Title Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity
Description AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A treatment-emergent AE is any AE either reported for first time or worsening of a pre-existing event after the first dose of study drug. Grade 1 AEs is defined as Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 AEs is defined as Moderate; minimal, local, or non-invasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3 AEs is defined as the severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living and Grade 4 AEs as life-threatening consequences; urgent intervention indicated. Data is reported for Grade 3 and higher severity for this outcome measure.
Time Frame From screening through 60 days after end of treatment, up to Month 15

Outcome Measure Data

Analysis Population Description
The full analysis set (FAS) included all participants enrolled in the study who received at least 1 dose of study drug.
Arm/Group Title Phase 1: 0.03 mg/kg Q2W Phase 1: 0.1 mg/kg Q2W Phase 1: 0.3 mg/kg Q2W Phase 1: 1.0 mg/kg Q2W Phase 1: 3.0 mg/kg Q2W Phase 1: 5.0 mg/kg Q2W Phase 1: 10.0 mg/kg Q2W Phase 1: 20.0 mg/kg Q2W Phase 1: 400 mg Q4W Phase 2: 300 mg Q2W
Arm/Group Description Participants received IV infusion of study drug at a dose of 0.03 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.1 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.3 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 1.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 3.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 5.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 10.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 20.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 400 mg Q4W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 300 mg Q2W starting on Day 1 of each cycle for up to 15 months.
Measure Participants 4 4 4 3 15 18 16 4 10 22
TEAEs
4
100%
4
100%
4
100%
3
100%
15
100%
18
100%
16
100%
4
100%
10
100%
22
100%
Grade 3 and Higher
3
75%
3
75%
1
25%
2
66.7%
8
53.3%
11
61.1%
9
56.3%
3
75%
3
30%
14
63.6%
2. Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax)
Description
Time Frame Day 1 of Cycles 1 and 6 post-dose

Outcome Measure Data

Analysis Population Description
The pharmacokinetic (PK) evaluable population included all participants who received at least 1 dose of study drug and provided at least 1 post dose sample (1 PK measurement).
Arm/Group Title Phase 1: 0.03 mg/kg Q2W Phase 1: 0.1 mg/kg Q2W Phase 1: 0.3 mg/kg Q2W Phase 1: 1.0 mg/kg Q2W Phase 1: 3.0 mg/kg Q2W Phase 1: 5.0 mg/kg Q2W Phase 1: 10.0 mg/kg Q2W Phase 1: 20.0 mg/kg Q2W Phase 1: 400 mg Q4W Phase 2: 300 mg Q2W
Arm/Group Description Participants received IV infusion of study drug at a dose of 0.03 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.1 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.3 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 1.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 3.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 5.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 10.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 20.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 400 mg Q4W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 300 mg Q2W starting on Day 1 of each cycle for up to 15 months.
Measure Participants 4 4 4 3 15 18 16 4 10 22
Cycle 1 (After the First Dose)
781
(135)
2700
(779)
6450
(1330)
21,600
(321)
66,000
(13,700)
128,000
(30,100)
283,000
(71,500)
437,000
(60,500)
127,000
(25,400)
103,000
(25,600)
Cycle 6
7420
(573)
36,500
(NA)
107,000
(25,500)
176,000
(65,700)
409,000
(97,000)
168,000
(28,500)
137,000
(21,900)
3. Secondary Outcome
Title Time to Maximum Concentration (Tmax)
Description
Time Frame Day 1 of Cycles 1 and 6 post-dose

Outcome Measure Data

Analysis Population Description
The PK evaluable population included all participants who received at least 1 dose of study drug and provided at least 1 post dose sample (1 PK measurement).
Arm/Group Title Phase 1: 0.03 mg/kg Q2W Phase 1: 0.1 mg/kg Q2W Phase 1: 0.3 mg/kg Q2W Phase 1: 1.0 mg/kg Q2W Phase 1: 3.0 mg/kg Q2W Phase 1: 5.0 mg/kg Q2W Phase 1: 10.0 mg/kg Q2W Phase 1: 20.0 mg/kg Q2W Phase 1: 400 mg Q4W Phase 2: 300 mg Q2W
Arm/Group Description Participants received IV infusion of study drug at a dose of 0.03 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.1 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.3 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 1.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 3.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 5.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 10.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 20.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 400 mg Q4W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 300 mg Q2W starting on Day 1 of each cycle for up to 15 months.
Measure Participants 4 4 4 3 15 18 16 4 10 22
Cycle 1 (After the First Dose)
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
Cycle 6
0.1
4.0
0.1
0.1
0.1
0.1
0.1
4. Secondary Outcome
Title Minimum Observed Plasma Concentration Over the Dose Interval (Cmin)
Description
Time Frame Day 1 of Cycles 2, 3, 4, 6, and 7 post-dose

Outcome Measure Data

Analysis Population Description
The PK evaluable population included all participants who received at least 1 dose of study drug and provided at least 1 post dose sample (1 PK measurement). Data is presented for those cycles for which data is available.
Arm/Group Title Phase 1: 0.03 mg/kg Q2W Phase 1: 0.1 mg/kg Q2W Phase 1: 0.3 mg/kg Q2W Phase 1: 1.0 mg/kg Q2W Phase 1: 3.0 mg/kg Q2W Phase 1: 5.0 mg/kg Q2W Phase 1: 10.0 mg/kg Q2W Phase 1: 20.0 mg/kg Q2W Phase 1: 400 mg Q4W Phase 2: 300 mg Q2W
Arm/Group Description Participants received IV infusion of study drug at a dose of 0.03 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.1 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.3 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 1.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 3.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 5.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 10.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 20.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 400 mg Q4W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 300 mg Q2W starting on Day 1 of each cycle for up to 15 months.
Measure Participants 4 4 4 4 15 18 16 4 10 22
Cycle 2
42.1
(48.8)
460
(131)
1110
(762)
4910
(1420)
14,800
(6160)
25,600
(12,100)
58,000
(23,900)
95,400
(33,300)
13,000
(10,100)
22,800
(5880)
Cycle 3
0.0
(0.0)
206
(187)
900
(1050)
8290
(5530)
23,500
(10,600)
36,200
(25,500)
89,200
(35,000)
117,000
(44,400)
22,800
(10,200)
36,800
(16,300)
Cycle 4
0.0
(0.0)
29.1
(50.5)
1390
(1230)
10,300
(NA)
25,700
(15,000)
46,700
(36,500)
135,000
(73,700)
135,000
(66,300)
20,500
(11,200)
31,600
(15,200)
Cycle 6
0.0
(0.0)
0.0
(0.0)
1210
(1260)
15,100
(NA)
34,900
(19,000)
71,800
(42,800)
133,000
(33,200)
21,300
(14,100)
42,400
(15,600)
Cycle 7
0.0
(0.0)
939
(1060)
15,500
(NA)
41,100
(16,700)
64,900
(34,800)
124,000
(42,100)
27,500
(18,300)
63,400
(53,500)
5. Secondary Outcome
Title Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t)
Description
Time Frame Day 1 of Cycles 1 and 6 post-dose

Outcome Measure Data

Analysis Population Description
The PK evaluable population included all participants who received at least 1 dose of study drug and provided at least 1 post dose sample (1 PK measurement).
Arm/Group Title Phase 1: 0.03 mg/kg Q2W Phase 1: 0.1 mg/kg Q2W Phase 1: 0.3 mg/kg Q2W Phase 1: 1.0 mg/kg Q2W Phase 1: 3.0 mg/kg Q2W Phase 1: 5.0 mg/kg Q2W Phase 1: 10.0 mg/kg Q2W Phase 1: 20.0 mg/kg Q2W Phase 1: 400 mg Q4W Phase 2: 300 mg Q2W
Arm/Group Description Participants received IV infusion of study drug at a dose of 0.03 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.1 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.3 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 1.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 3.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 5.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 10.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 20.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 400 mg Q4W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 300 mg Q2W starting on Day 1 of each cycle for up to 15 months.
Measure Participants 4 4 4 3 15 18 16 4 10 22
Cycle 1 (After the First Dose)
70.7
(29.0)
302
(115)
850
(108)
3130
(254)
8880
(2710)
17,900
(4970)
39,800
(10,300)
67,500
(7920)
25,400
(10,000)
13,400
(3520)
Cycle 6
1070
(392)
7190
(NA)
16,200
(10,000)
33,700
(17,400)
79,000
(13,400)
42,100
(19,500)
22,000
(6640)
6. Secondary Outcome
Title Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST)
Description ORR is defined as the percentage of participants having complete response (CR) or partial response (PR), as determined by investigator assessment of radiographic disease assessments. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
Time Frame Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months

Outcome Measure Data

Analysis Population Description
The FAS included all participants enrolled in the study who received at least 1 dose of study drug.
Arm/Group Title Phase 1: 0.03 mg/kg Q2W Phase 1: 0.1 mg/kg Q2W Phase 1: 0.3 mg/kg Q2W Phase 1: 1.0 mg/kg Q2W Phase 1: 3.0 mg/kg Q2W Phase 1: 5.0 mg/kg Q2W Phase 1: 10.0 mg/kg Q2W Phase 1: 20.0 mg/kg Q2W Phase 1: 400 mg Q4W Phase 2: 300 mg Q2W
Arm/Group Description Participants received IV infusion of study drug at a dose of 0.03 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.1 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.3 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 1.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 3.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 5.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 10.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 20.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 400 mg Q4W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 300 mg Q2W starting on Day 1 of each cycle for up to 15 months.
Measure Participants 4 4 4 3 15 18 16 4 10 22
RECIST v1.1
0.0
0%
0.0
0%
25.0
625%
0.0
0%
0.0
0%
0.0
0%
0.0
0%
0.0
0%
0.0
0%
4.5
20.5%
mRECIST v1.1
0.0
0%
0.0
0%
25.0
625%
0.0
0%
0.0
0%
0.0
0%
0.0
0%
0.0
0%
0.0
0%
0.0
0%
7. Secondary Outcome
Title Duration of Response (DOR) Per RECIST and mRECIST
Description DOR is defined as the time from earliest date of disease response (CR or PR) until earliest date of disease progression, as determined by investigator assessment of radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
Time Frame Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months

Outcome Measure Data

Analysis Population Description
The FAS included all participants enrolled in the study who received at least 1 dose of study drug.
Arm/Group Title Phase 1: 0.03 mg/kg Q2W Phase 1: 0.1 mg/kg Q2W Phase 1: 0.3 mg/kg Q2W Phase 1: 1.0 mg/kg Q2W Phase 1: 3.0 mg/kg Q2W Phase 1: 5.0 mg/kg Q2W Phase 1: 10.0 mg/kg Q2W Phase 1: 20.0 mg/kg Q2W Phase 1: 400 mg Q4W Phase 2: 300 mg Q2W
Arm/Group Description Participants received IV infusion of study drug at a dose of 0.03 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.1 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.3 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 1.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 3.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 5.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 10.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 20.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 400 mg Q4W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 300 mg Q2W starting on Day 1 of each cycle for up to 15 months.
Measure Participants 4 4 4 3 15 18 16 4 10 22
RECIST v1.1
NA
NA
169.0
NA
NA
NA
NA
NA
NA
NA
mRECIST v1.1
NA
NA
169.0
NA
NA
NA
NA
NA
NA
NA
8. Secondary Outcome
Title Duration of Disease Control Per RECIST and mRECIST
Description Duration of disease control (CR, PR, and stable disease [SD]), as measured from first report of SD or better until disease progression, as determined by investigator assessment of radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time Frame Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months

Outcome Measure Data

Analysis Population Description
The FAS included all participants enrolled in the study who received at least 1 dose of study drug.
Arm/Group Title Phase 1: 0.03 mg/kg Q2W Phase 1: 0.1 mg/kg Q2W Phase 1: 0.3 mg/kg Q2W Phase 1: 1.0 mg/kg Q2W Phase 1: 3.0 mg/kg Q2W Phase 1: 5.0 mg/kg Q2W Phase 1: 10.0 mg/kg Q2W Phase 1: 20.0 mg/kg Q2W Phase 1: 400 mg Q4W Phase 2: 300 mg Q2W
Arm/Group Description Participants received IV infusion of study drug at a dose of 0.03 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.1 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.3 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 1.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 3.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 5.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 10.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 20.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 400 mg Q4W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 300 mg Q2W starting on Day 1 of each cycle for up to 15 months.
Measure Participants 4 4 4 3 15 18 16 4 10 22
RECIST v1.1
NA
NA
169.0
91.0
58.5
58.0
62.0
61.0
113.0
213.0
mRECIST v1.1
NA
NA
169.0
91.0
58.5
58.0
62.0
61.0
113.0
213.0
9. Secondary Outcome
Title Progression Free Survival (PFS) Per RECIST and mRECIST
Description PFS is defined as the time from date of first dose of study drug until the earliest date of disease progression, as determined by investigator assessment of objective radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. Progression is defined by RECIST and mRECIST as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and an absolute lesion increase of at least 5 mm or the appearance of new lesions.
Time Frame Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months

Outcome Measure Data

Analysis Population Description
The FAS included all participants enrolled in the study who received at least 1 dose of study drug.
Arm/Group Title Phase 1: 0.03 mg/kg Q2W Phase 1: 0.1 mg/kg Q2W Phase 1: 0.3 mg/kg Q2W Phase 1: 1.0 mg/kg Q2W Phase 1: 3.0 mg/kg Q2W Phase 1: 5.0 mg/kg Q2W Phase 1: 10.0 mg/kg Q2W Phase 1: 20.0 mg/kg Q2W Phase 1: 400 mg Q4W Phase 2: 300 mg Q2W
Arm/Group Description Participants received IV infusion of study drug at a dose of 0.03 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.1 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.3 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 1.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 3.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 5.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 10.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 20.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 400 mg Q4W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 300 mg Q2W starting on Day 1 of each cycle for up to 15 months.
Measure Participants 4 4 4 3 15 18 16 4 10 22
PFS under RECIST v1.1
1.64
1.84
6.70
1.48
1.87
1.87
1.84
2.78
2.14
1.87
PFS under mRECIST v1.1
1.64
1.84
6.70
1.48
1.87
1.87
1.84
2.78
2.14
1.87

Adverse Events

Time Frame From screening through 60 days after end of treatment, up to Month 15
Adverse Event Reporting Description
Arm/Group Title Phase 1: 0.03 mg/kg Q2W Phase 1: 0.1 mg/kg Q2W Phase 1: 0.3 mg/kg Q2W Phase 1: 1.0 mg/kg Q2W Phase 1: 3.0 mg/kg Q2W Phase 1: 5.0 mg/kg Q2W Phase 1: 10.0 mg/kg Q2W Phase 1: 20.0 mg/kg Q2W Phase 1: 400 mg Q4W Phase 2: 300 mg Q2W Total
Arm/Group Description Participants received IV infusion of study drug at a dose of 0.03 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.1 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 0.3 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 1.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 3.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 5.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 10.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 20.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 400 mg Q4W starting on Day 1 of each cycle for up to 15 months. Participants received IV infusion of study drug at a dose of 300 mg Q2W starting on Day 1 of each cycle for up to 15 months. Total
All Cause Mortality
Phase 1: 0.03 mg/kg Q2W Phase 1: 0.1 mg/kg Q2W Phase 1: 0.3 mg/kg Q2W Phase 1: 1.0 mg/kg Q2W Phase 1: 3.0 mg/kg Q2W Phase 1: 5.0 mg/kg Q2W Phase 1: 10.0 mg/kg Q2W Phase 1: 20.0 mg/kg Q2W Phase 1: 400 mg Q4W Phase 2: 300 mg Q2W 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 Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 2/4 (50%) 3/4 (75%) 1/4 (25%) 1/3 (33.3%) 4/15 (26.7%) 5/18 (27.8%) 3/16 (18.8%) 1/4 (25%) 1/10 (10%) 5/22 (22.7%) 26/100 (26%)
Serious Adverse Events
Phase 1: 0.03 mg/kg Q2W Phase 1: 0.1 mg/kg Q2W Phase 1: 0.3 mg/kg Q2W Phase 1: 1.0 mg/kg Q2W Phase 1: 3.0 mg/kg Q2W Phase 1: 5.0 mg/kg Q2W Phase 1: 10.0 mg/kg Q2W Phase 1: 20.0 mg/kg Q2W Phase 1: 400 mg Q4W Phase 2: 300 mg Q2W 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 Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 3/4 (75%) 3/4 (75%) 1/4 (25%) 2/3 (66.7%) 6/15 (40%) 6/18 (33.3%) 7/16 (43.8%) 2/4 (50%) 3/10 (30%) 10/22 (45.5%) 43/100 (43%)
Blood and lymphatic system disorders
Anaemia 1/4 (25%) 1 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 2 2/100 (2%) 3
Cardiac disorders
Acute left ventricular failure 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Acute myocardial infarction 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 2 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 2/100 (2%) 3
Atrial fibrillation 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 1/100 (1%) 1
Cardiac arrest 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Cardiac tamponade 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Cardiac ventricular thrombosis 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Cardio-respiratory arrest 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Cardiogenic shock 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Endocrine disorders
Adrenal insufficiency 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Gastrointestinal disorders
Abdominal pain 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 2/4 (50%) 2 1/10 (10%) 1 1/22 (4.5%) 1 5/100 (5%) 5
Ascites 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Diarrhoea 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 2/100 (2%) 2
Gastrointestinal haemorrhage 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 1/100 (1%) 1
Large intestinal obstruction 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 2 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 2
Nausea 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 1/100 (1%) 1
Small intestinal obstruction 1/4 (25%) 1 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 2 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 2/100 (2%) 3
Upper gastrointestinal haemorrhage 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 1/100 (1%) 1
General disorders
Chills 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 1/100 (1%) 1
Fatigue 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 2/100 (2%) 2
Non-cardiac chest pain 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Oedema peripheral 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 1/100 (1%) 1
Perforation 0/4 (0%) 0 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Pyrexia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 2 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/22 (0%) 0 2/100 (2%) 3
Hepatobiliary disorders
Bile duct obstruction 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Cholangitis 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Hepatic haemorrhage 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Infections and infestations
Corona virus infection 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/22 (0%) 0 1/100 (1%) 1
Escherichia infection 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Lung infection 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Pneumonia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 2/100 (2%) 2
Pyelonephritis 1/4 (25%) 1 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Sepsis 1/4 (25%) 1 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 3/100 (3%) 3
Septic shock 1/4 (25%) 1 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Soft tissue infection 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Urinary tract infection 1/4 (25%) 1 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 2/100 (2%) 2
Injury, poisoning and procedural complications
Procedural pain 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Investigations
Alanine aminotransferase increased 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Aspartate aminotransferase increased 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Metabolism and nutrition disorders
Dehydration 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 3/100 (3%) 3
Failure to thrive 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 1/100 (1%) 1
Hypoglycaemia 0/4 (0%) 0 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Hyponatraemia 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 2/100 (2%) 2
Musculoskeletal and connective tissue disorders
Back pain 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 1/3 (33.3%) 1 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 2/100 (2%) 2
Muscular weakness 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Pain in extremity 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression 1/4 (25%) 1 1/4 (25%) 1 0/4 (0%) 0 1/3 (33.3%) 1 1/15 (6.7%) 1 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 4/22 (18.2%) 4 10/100 (10%) 10
Nervous system disorders
Brain oedema 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Seizure 0/4 (0%) 0 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Thrombotic stroke 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Transient ischaemic attack 0/4 (0%) 0 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Psychiatric disorders
Confusional state 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Delirium 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 1/100 (1%) 1
Mental status changes 0/4 (0%) 0 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Renal and urinary disorders
Acute kidney injury 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 1/22 (4.5%) 1 2/100 (2%) 2
Hydronephrosis 1/4 (25%) 2 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 2/100 (2%) 3
Urinary tract obstruction 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Respiratory, thoracic and mediastinal disorders
Bronchiectasis 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/22 (0%) 0 1/100 (1%) 1
Chronic obstructive pulmonary disease 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/22 (0%) 0 1/100 (1%) 1
Cough 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Dyspnoea 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 2 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 2/22 (9.1%) 2 4/100 (4%) 5
Haemoptysis 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 1/100 (1%) 1
Pleural effusion 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/22 (0%) 0 2/100 (2%) 2
Respiratory distress 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 1/100 (1%) 1
Respiratory failure 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 2/100 (2%) 2
Vascular disorders
Embolism 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 2/100 (2%) 2
Other (Not Including Serious) Adverse Events
Phase 1: 0.03 mg/kg Q2W Phase 1: 0.1 mg/kg Q2W Phase 1: 0.3 mg/kg Q2W Phase 1: 1.0 mg/kg Q2W Phase 1: 3.0 mg/kg Q2W Phase 1: 5.0 mg/kg Q2W Phase 1: 10.0 mg/kg Q2W Phase 1: 20.0 mg/kg Q2W Phase 1: 400 mg Q4W Phase 2: 300 mg Q2W 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 Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 4/4 (100%) 3/4 (75%) 4/4 (100%) 3/3 (100%) 15/15 (100%) 18/18 (100%) 16/16 (100%) 4/4 (100%) 10/10 (100%) 22/22 (100%) 99/100 (99%)
Blood and lymphatic system disorders
Anaemia 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 2/15 (13.3%) 2 4/18 (22.2%) 4 3/16 (18.8%) 3 0/4 (0%) 0 1/10 (10%) 2 4/22 (18.2%) 4 15/100 (15%) 16
Iron deficiency anaemia 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Leukopenia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 2 0/22 (0%) 0 1/100 (1%) 2
Lymph node pain 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Thrombocytopenia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 2/15 (13.3%) 3 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 2/100 (2%) 3
Cardiac disorders
Atrial fibrillation 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Pericardial effusion 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Pericarditis constrictive 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Sinus tachycardia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 2 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 2/22 (9.1%) 2 3/100 (3%) 4
Ear and labyrinth disorders
Tinnitus 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Endocrine disorders
Adrenal insufficiency 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 2/100 (2%) 2
Hyperthyroidism 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 2/100 (2%) 2
Hypothyroidism 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 4/100 (4%) 4
Eye disorders
Conjunctival haemorrhage 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Dry eye 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Eye pain 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Photophobia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Vision blurred 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Gastrointestinal disorders
Abdominal distension 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Abdominal pain 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 2/3 (66.7%) 2 3/15 (20%) 4 3/18 (16.7%) 4 8/16 (50%) 9 2/4 (50%) 2 2/10 (20%) 2 1/22 (4.5%) 1 22/100 (22%) 25
Abdominal pain lower 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 2/15 (13.3%) 2 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 4/100 (4%) 4
Abdominal pain upper 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 2/100 (2%) 2
Ascites 0/4 (0%) 0 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 1/4 (25%) 1 1/10 (10%) 1 1/22 (4.5%) 1 5/100 (5%) 5
Breath odour 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Constipation 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 5/18 (27.8%) 5 1/16 (6.3%) 1 1/4 (25%) 1 0/10 (0%) 0 3/22 (13.6%) 3 11/100 (11%) 11
Diarrhoea 1/4 (25%) 1 0/4 (0%) 0 1/4 (25%) 2 0/3 (0%) 0 3/15 (20%) 4 4/18 (22.2%) 7 2/16 (12.5%) 2 1/4 (25%) 1 0/10 (0%) 0 3/22 (13.6%) 3 15/100 (15%) 20
Dry mouth 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 2/18 (11.1%) 2 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 3/100 (3%) 3
Dyspepsia 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/15 (0%) 0 2/18 (11.1%) 2 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 1/22 (4.5%) 1 5/100 (5%) 5
Dysphagia 0/4 (0%) 0 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 4/100 (4%) 4
Faeces discoloured 0/4 (0%) 0 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Flatulence 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 3/100 (3%) 3
Gastritis 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Gastrointestinal pain 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Gastrooesophageal reflux disease 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 2/15 (13.3%) 2 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 1/10 (10%) 1 2/22 (9.1%) 2 7/100 (7%) 7
Haemorrhoids 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Intra-abdominal haematoma 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Lip swelling 1/4 (25%) 1 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Nausea 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 3 1/3 (33.3%) 1 3/15 (20%) 3 5/18 (27.8%) 6 6/16 (37.5%) 7 1/4 (25%) 1 2/10 (20%) 2 5/22 (22.7%) 6 24/100 (24%) 29
Rectal polyp 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Salivary hypersecretion 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Toothache 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Vomiting 1/4 (25%) 1 1/4 (25%) 1 1/4 (25%) 3 0/3 (0%) 0 3/15 (20%) 5 3/18 (16.7%) 3 5/16 (31.3%) 5 2/4 (50%) 3 1/10 (10%) 1 2/22 (9.1%) 2 19/100 (19%) 24
General disorders
Asthenia 2/4 (50%) 2 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 4/100 (4%) 4
Axillary pain 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Chest pain 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 2/100 (2%) 2
Chills 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 1/15 (6.7%) 1 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 1/22 (4.5%) 1 5/100 (5%) 5
Face oedema 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 2/100 (2%) 2
Fatigue 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 1/3 (33.3%) 1 6/15 (40%) 6 5/18 (27.8%) 5 7/16 (43.8%) 8 2/4 (50%) 2 5/10 (50%) 5 11/22 (50%) 12 38/100 (38%) 40
Generalised oedema 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Influenza like illness 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 1/4 (25%) 2 1/10 (10%) 1 3/22 (13.6%) 3 7/100 (7%) 8
Local swelling 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Localised oedema 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Malaise 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 2/15 (13.3%) 2 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 3/100 (3%) 3
Mucosal inflammation 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Nodule 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Non-cardiac chest pain 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 2/15 (13.3%) 2 2/18 (11.1%) 2 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 5/100 (5%) 5
Oedema peripheral 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 3/15 (20%) 3 5/18 (27.8%) 6 0/16 (0%) 0 1/4 (25%) 1 1/10 (10%) 1 5/22 (22.7%) 6 16/100 (16%) 18
Pain 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 2/16 (12.5%) 2 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 3/100 (3%) 3
Peripheral swelling 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Pyrexia 2/4 (50%) 2 0/4 (0%) 0 2/4 (50%) 2 1/3 (33.3%) 1 2/15 (13.3%) 3 2/18 (11.1%) 4 5/16 (31.3%) 5 0/4 (0%) 0 1/10 (10%) 1 4/22 (18.2%) 4 19/100 (19%) 22
Immune system disorders
Hypersensitivity 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 2/18 (11.1%) 3 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 2/100 (2%) 3
Infections and infestations
Cellulitis 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Conjunctivitis 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Cystitis 0/4 (0%) 0 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Fungal infection 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Gastroenteritis 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Herpes zoster 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 2/100 (2%) 2
Influenza 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/22 (0%) 0 1/100 (1%) 1
Lower respiratory tract infection bacterial 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 2 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 2
Mucosal infection 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 2 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 2
Oral candidiasis 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/22 (0%) 0 1/100 (1%) 1
Pneumonia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 1/22 (4.5%) 1 3/100 (3%) 3
Sinusitis 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 2/100 (2%) 2
Skin infection 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 3 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 2/100 (2%) 4
Systemic infection 1/4 (25%) 1 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Upper respiratory tract infection 1/4 (25%) 1 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 2 3/22 (13.6%) 3 6/100 (6%) 7
Urinary tract infection 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 3/22 (13.6%) 3 5/100 (5%) 5
Viral infection 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Injury, poisoning and procedural complications
Burns second degree 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Fall 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 2/22 (9.1%) 3 2/100 (2%) 3
Post procedural contusion 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Post procedural discharge 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Procedural pain 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Spinal fracture 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Wound 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 2/100 (2%) 2
Investigations
Activated partial thromboplastin time prolonged 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 2/100 (2%) 2
Alanine aminotransferase increased 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 2/15 (13.3%) 2 2/18 (11.1%) 2 2/16 (12.5%) 2 1/4 (25%) 1 0/10 (0%) 0 1/22 (4.5%) 1 8/100 (8%) 8
Amylase increased 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 2/15 (13.3%) 2 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 2/100 (2%) 2
Aspartate aminotransferase increased 1/4 (25%) 1 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 2/15 (13.3%) 2 1/18 (5.6%) 1 2/16 (12.5%) 2 1/4 (25%) 1 0/10 (0%) 0 1/22 (4.5%) 1 8/100 (8%) 8
Blood alkaline phosphatase increased 1/4 (25%) 1 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 2/18 (11.1%) 2 3/16 (18.8%) 3 1/4 (25%) 1 0/10 (0%) 0 2/22 (9.1%) 2 10/100 (10%) 10
Blood bilirubin increased 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 1/15 (6.7%) 1 1/18 (5.6%) 1 1/16 (6.3%) 1 1/4 (25%) 1 0/10 (0%) 0 0/22 (0%) 0 5/100 (5%) 5
Blood creatine increased 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Blood creatine phosphokinase increased 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Blood creatinine increased 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Blood lactic acid increased 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Blood phosphorus decreased 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Gamma-glutamyltransferase increased 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 2/15 (13.3%) 2 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 3/100 (3%) 3
Globulins increased 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Grip strength decreased 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Lipase increased 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 2/15 (13.3%) 2 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 3/100 (3%) 3
Transaminases increased 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Troponin I increased 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Weight decreased 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 1/15 (6.7%) 1 2/18 (11.1%) 2 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 5/100 (5%) 5
Metabolism and nutrition disorders
Decreased appetite 0/4 (0%) 0 1/4 (25%) 1 0/4 (0%) 0 1/3 (33.3%) 1 4/15 (26.7%) 4 2/18 (11.1%) 2 3/16 (18.8%) 3 2/4 (50%) 3 3/10 (30%) 3 4/22 (18.2%) 4 20/100 (20%) 21
Dehydration 1/4 (25%) 1 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 1/16 (6.3%) 1 1/4 (25%) 1 2/10 (20%) 2 3/22 (13.6%) 4 9/100 (9%) 10
Hypercalcaemia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 2/100 (2%) 2
Hyperkalaemia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Hyperuricaemia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Hypoalbuminaemia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 2/15 (13.3%) 2 1/18 (5.6%) 1 0/16 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/22 (0%) 0 4/100 (4%) 4
Hypocalcaemia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Hypoglycaemia 0/4 (0%) 0 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Hypokalaemia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 3/22 (13.6%) 3 3/100 (3%) 3
Hyponatraemia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 2/18 (11.1%) 2 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 2/22 (9.1%) 2 5/100 (5%) 5
Hypophosphataemia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 3 3/100 (3%) 5
Musculoskeletal and connective tissue disorders
Arthralgia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 3/18 (16.7%) 3 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 5/100 (5%) 5
Back pain 1/4 (25%) 1 0/4 (0%) 0 1/4 (25%) 2 1/3 (33.3%) 1 1/15 (6.7%) 1 0/18 (0%) 0 2/16 (12.5%) 2 0/4 (0%) 0 1/10 (10%) 1 2/22 (9.1%) 2 9/100 (9%) 10
Clubbing 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Flank pain 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 1/22 (4.5%) 1 3/100 (3%) 3
Muscle spasms 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Muscular weakness 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 4/22 (18.2%) 5 5/100 (5%) 6
Musculoskeletal chest pain 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 2/100 (2%) 2
Musculoskeletal pain 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Myalgia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 2/15 (13.3%) 2 2/18 (11.1%) 2 1/16 (6.3%) 1 0/4 (0%) 0 1/10 (10%) 1 1/22 (4.5%) 1 7/100 (7%) 7
Pain in extremity 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 2 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 3/22 (13.6%) 3 4/100 (4%) 5
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/22 (0%) 0 2/100 (2%) 2
Squamous cell carcinoma of skin 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 2/22 (9.1%) 2 2/100 (2%) 2
Tumour pain 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 2 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 1/22 (4.5%) 1 3/100 (3%) 4
Nervous system disorders
Burning sensation 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/22 (0%) 0 1/100 (1%) 1
Dizziness 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 2/15 (13.3%) 2 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 3/22 (13.6%) 3 6/100 (6%) 6
Dysgeusia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Headache 0/4 (0%) 0 1/4 (25%) 1 2/4 (50%) 2 1/3 (33.3%) 1 2/15 (13.3%) 3 4/18 (22.2%) 4 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 2/22 (9.1%) 2 12/100 (12%) 13
Memory impairment 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Paraesthesia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 2/22 (9.1%) 2 3/100 (3%) 3
Peripheral motor neuropathy 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 2/100 (2%) 2
Peripheral sensory neuropathy 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Peroneal nerve palsy 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Psychiatric disorders
Affect lability 0/4 (0%) 0 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Anhedonia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Anxiety 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 2/16 (12.5%) 2 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 4/100 (4%) 4
Confusional state 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Depression 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 3/18 (16.7%) 3 0/16 (0%) 0 1/4 (25%) 1 1/10 (10%) 1 1/22 (4.5%) 1 6/100 (6%) 6
Insomnia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 3/18 (16.7%) 3 2/16 (12.5%) 2 0/4 (0%) 0 0/10 (0%) 0 2/22 (9.1%) 2 7/100 (7%) 7
Renal and urinary disorders
Acute kidney injury 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 2/100 (2%) 2
Dysuria 1/4 (25%) 1 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/22 (0%) 0 2/100 (2%) 2
Haematuria 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 3/100 (3%) 3
Lower urinary tract symptoms 1/4 (25%) 1 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Nephritis 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Proteinuria 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Urinary incontinence 1/4 (25%) 1 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 2/22 (9.1%) 2 3/100 (3%) 3
Reproductive system and breast disorders
Pelvic pain 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/22 (0%) 0 1/100 (1%) 1
Cough 0/4 (0%) 0 0/4 (0%) 0 2/4 (50%) 4 0/3 (0%) 0 4/15 (26.7%) 4 1/18 (5.6%) 1 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 5/22 (22.7%) 5 13/100 (13%) 15
Dysphonia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Dyspnoea 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 2/3 (66.7%) 2 6/15 (40%) 7 4/18 (22.2%) 4 3/16 (18.8%) 3 1/4 (25%) 1 3/10 (30%) 4 5/22 (22.7%) 5 24/100 (24%) 26
Epistaxis 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Haemoptysis 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/22 (0%) 0 1/100 (1%) 1
Hiccups 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 2/100 (2%) 2
Hypoxia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 1/22 (4.5%) 1 2/100 (2%) 2
Nasal congestion 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 0/15 (0%) 0 2/18 (11.1%) 2 2/16 (12.5%) 2 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 5/100 (5%) 5
Oropharyngeal pain 1/4 (25%) 1 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 2/22 (9.1%) 2 3/100 (3%) 3
Pleural effusion 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/15 (0%) 0 1/18 (5.6%) 1 2/16 (12.5%) 2 0/4 (0%) 0 1/10 (10%) 1 1/22 (4.5%) 1 6/100 (6%) 6
Pleurisy 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Pneumonitis 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Productive cough 0/4 (0%) 0 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 2/100 (2%) 2
Upper-airway cough syndrome 0/4 (0%) 0 0/4 (0%) 0 1/4 (25%) 1 0/3 (0%) 0 1/15 (6.7%) 1 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 3/100 (3%) 3
Skin and subcutaneous tissue disorders
Dry skin 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 2/18 (11.1%) 2 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 3/100 (3%) 3
Erythema nodosum 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/22 (0%) 0 1/100 (1%) 1
Night sweats 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 1/10 (10%) 1 1/22 (4.5%) 1 3/100 (3%) 3
Pruritus 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 5/15 (33.3%) 6 5/18 (27.8%) 6 3/16 (18.8%) 3 0/4 (0%) 0 1/10 (10%) 1 2/22 (9.1%) 2 17/100 (17%) 19
Pruritus generalised 1/4 (25%) 1 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 3/15 (20%) 3 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 2/10 (20%) 2 1/22 (4.5%) 1 8/100 (8%) 8
Rash 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 2/15 (13.3%) 2 2/18 (11.1%) 2 2/16 (12.5%) 2 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 6/100 (6%) 6
Rash generalised 1/4 (25%) 3 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 2/15 (13.3%) 3 2/18 (11.1%) 2 1/16 (6.3%) 2 0/4 (0%) 0 1/10 (10%) 1 1/22 (4.5%) 1 8/100 (8%) 12
Rash maculo-papular 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 3/15 (20%) 3 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 2 1/22 (4.5%) 1 6/100 (6%) 7
Rash papular 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Skin hyperpigmentation 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/22 (0%) 0 1/100 (1%) 1
Skin ulcer 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 2/18 (11.1%) 2 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 2/100 (2%) 2
Telangiectasia 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Urticaria 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 0/18 (0%) 0 0/16 (0%) 0 0/4 (0%) 0 1/10 (10%) 1 0/22 (0%) 0 1/100 (1%) 1
Social circumstances
Denture wearer 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Vascular disorders
Deep vein thrombosis 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1
Embolism 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 1/3 (33.3%) 1 0/15 (0%) 0 1/18 (5.6%) 2 0/16 (0%) 0 1/4 (25%) 1 0/10 (0%) 0 1/22 (4.5%) 1 4/100 (4%) 5
Hypertension 0/4 (0%) 0 1/4 (25%) 1 0/4 (0%) 0 0/3 (0%) 0 2/15 (13.3%) 2 1/18 (5.6%) 1 2/16 (12.5%) 2 0/4 (0%) 0 1/10 (10%) 1 1/22 (4.5%) 1 8/100 (8%) 8
Hypotension 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 1/16 (6.3%) 1 0/4 (0%) 0 0/10 (0%) 0 2/22 (9.1%) 2 4/100 (4%) 4
Lymphoedema 0/4 (0%) 0 0/4 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/15 (0%) 0 1/18 (5.6%) 1 0/16 (0%) 0 0/4 (0%) 0 0/10 (0%) 0 0/22 (0%) 0 1/100 (1%) 1

Limitations/Caveats

[Not Specified]

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 855-463-3463
Email medinfo@incyte.com
Responsible Party:
Incyte Biosciences International Sàrl
ClinicalTrials.gov Identifier:
NCT02697591
Other Study ID Numbers:
  • INCAGN 1876-101
First Posted:
Mar 3, 2016
Last Update Posted:
Feb 26, 2021
Last Verified:
Feb 1, 2021