Phase 1/2a Dose-Escalation Study of CRLX301 in Patients With Advanced Solid Tumors
Sponsor
NewLink Genetics Corporation (Industry)
Overall Status
Terminated
CT.gov ID
NCT02380677
Collaborator
(none)
42
3
12
30.1
14
0.5
Study Details
Study Description
Brief Summary
A Phase 1/2a, open-label, dose-escalation study with enrollment in Phase 1 to continue until determination of the Maximum Tolerated Dose (MTD) /Recommended Phase 2a Dose (RP2D), and then enrollment into Phase 2a expansion cohorts will be initiated.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
Phase 1 is an open-label, dose-escalation protocol. It is anticipated that up to 36 patients will be enrolled in Phase 1. All patients will be assigned to treatment with CRLX301 as the single agent.
For the first 2 cohorts a 1+5 study design will be utilized. A single patient will be enrolled sequentially into cohort 1 and cohort 2. If either patient in cohort 1 or 2 experiences a dose limiting toxicity (DLT) during Cycle 1, then the cohort will be expanded to enroll additional patients up to a total of 6.
As of cohort 3 and for all subsequent cohorts, a 3+3 dose escalation schema will be utilized.
MTD/RP2D will be determined at the dose level when <2 of 6 patients experience a DLT in a cohort.
The Phase 2a part of the study will be an open-label expansion cohort study. An additional 24 patients with advanced, histologically confirmed solid tumor malignancies will be enrolled. All patients will be assigned to treatment at the MTD/RP2D with CRLX301 as the single agent.
All patients will be followed for safety, tumor response, and progression free survival (PFS) all per RECIST version 1.1 guidelines. Patients will remain on study treatment until they experience progression of disease, unacceptable toxicity, or other specified reason for discontinuation.
Study Design
Study Type:
Interventional
Actual Enrollment
:
42 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
Phase 1 dose escalation study followed by phase 2a expansion cohortPhase 1 dose escalation study followed by phase 2a expansion cohort
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1/2a Dose-Escalation Study of CRLX301 in Patients With Advanced Solid Tumor Malignancies
Study Start Date
:
Apr 1, 2015
Actual Primary Completion Date
:
Oct 4, 2017
Actual Study Completion Date
:
Oct 4, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Schedule 1 Cohort 1 CRLX301 7.5 mg/m2 IV given every 3 weeks |
Drug: CRLX301
|
| Experimental: Schedule 1 Cohort 2 CRLX301 15 mg/m2 IV given every 3 weeks |
Drug: CRLX301
|
| Experimental: Schedule 1 Cohort 3 CRLX301 30 mg/m2 IV given every 3 weeks |
Drug: CRLX301
|
| Experimental: Schedule 1 Cohort 4 CRLX301 60 mg/m2 IV given every 3 weeks |
Drug: CRLX301
|
| Experimental: Schedule 1 Cohort 5 CRLX301 75 mg/m2 IV given every 3 weeks |
Drug: CRLX301
|
| Experimental: Schedule 1 Cohort 6 CRLX301 90 mg/m2 IV given every 3 weeks |
Drug: CRLX301
|
| Experimental: Schedule 2 Cohort 1 CRLX301 25 mg/m2 IV given weekly |
Drug: CRLX301
|
| Experimental: Schedule 2 Cohort 2 CRLX301 35 mg/m2 IV given weekly |
Drug: CRLX301
|
| Experimental: Schedule 2 Cohort 3 CRLX301 45 mg/m2 IV given weekly |
Drug: CRLX301
|
| Experimental: Schedule 2 Cohort 4 CRLX301 54 mg/m2 IV given weekly |
Drug: CRLX301
|
| Experimental: Schedule 2 Cohort 5 CRLX301 54 mg/m2 given weekly for 3 weeks with 1 week off |
Drug: CRLX301
|
| Experimental: Phase 2a expansion cohort CRLX301 75mg/m2 IV given every 3 weeks |
Drug: CRLX301
|
Outcome Measures
Primary Outcome Measures
- Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities [13 to 19 months]
Determination of MTD is dependent upon number of dose limiting toxicities and significant adverse events observed.
- Number of Phase 2a Participants With Adverse Events as a Measure of Safety and Tolerability [12 months]
Safety variables will include AEs, SAEs, Severe AEs, Related AEs and AEs leading to Discontinuation in phase 2a subjects.
Secondary Outcome Measures
- Evaluate the Pharmacokinetic (PK) Profile of CRLX301 [2.5 years]
Area under the concentration vs time curve of released docetaxel in blood and/or urine specimens of patients receiving at least 1 dose of CRLX301.
- Percentage of Participants Stratified by Best Overall Tumor Response [2.5 years]
Best overall tumor response will be provided per dose cohort using RECIST 1.1
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Male or female ≥18 years of age
-
Diagnosis of histologically or cytologically confirmed, advanced solid tumor malignancy that is refractory to or not a candidate for standard therapy
-
ECOG 0 or 1
-
Life expectancy >12 weeks
-
Fertile males or females of childbearing potential agree to use adequate contraception prior to study entry
-
Negative urine pregnancy test
Exclusion Criteria:
-
Uncontrolled grade 2 or greater toxicity except alopecia
-
Prolongation of QT/QTc interval
-
Women who are pregnant or nursing
-
Any known HIV infection or AIDS or any concurrent infection requiring IV antibiotics
-
Any chronic or concurrent acute liver disease, including viral hepatitis
-
Primary brain malignant tumors
-
Known metastases to the brain
-
Uncontrolled hypertension
-
Concurrent participation in any other investigational study
-
Concurrent treatment with anticoagulation medication, unless approved by Sponsor
-
History of stroke, deep venous thrombosis (DVT), or transient ischemic attack (TIA)
-
History of other cancer type, except for cutaneous basal cell or squamous cell carcinoma, or cervical or prostate cancer in situ, within the last 2 years prior to C1D1
-
Uncontrolled concurrent disease or illness
-
History of severe hypersensitivity reaction to taxanes
-
Peripheral neuropathy exclusions
-
Other condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | United States | 27599 |
| 2 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 3 | MD Anderson | Houston | Texas | United States |
Sponsors and Collaborators
- NewLink Genetics Corporation
Investigators
- Principal Investigator: Elizabeth Dees, MD, University of North Carolina
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
NewLink Genetics Corporation
ClinicalTrials.gov Identifier:
NCT02380677
Other Study ID Numbers:
- CRLX301-101
First Posted:
Mar 5, 2015
Last Update Posted:
Jun 9, 2020
Last Verified:
May 1, 2020
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Schedule 1 Cohort 1 | Schedule 1 Cohort 2 | Schedule 1 Cohort 3 | Schedule 1 Cohort 5 | Schedule 1 Cohort 6 | Schedule 1 Cohort 7 | Schedule 2 Cohort 1 | Schedule 2 Cohort 2 | Schedule 2 Cohort 3 | Schedule 2 Cohort 4 | Schedule 2 Cohort 5 | Phase 2a Expansion Cohort |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | CRLX301 7.5 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 15 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 30 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 60 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 75 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 90 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 25 mg/m2 IV given weekly CRLX301 | CRLX301 35 mg/m2 IV given weekly CRLX301 | CRLX301 45 mg/m2 IV given weekly CRLX301 | CRLX301 54 mg/m2 IV given weekly CRLX301 | CRLX301 54 mg/m2 given weekly for 3 weeks with 1 week off CRLX301 | CRLX301 75mg/m2 IV given every 3 weeks CRLX301 |
| Period Title: Overall Study | ||||||||||||
| STARTED | 1 | 1 | 3 | 3 | 6 | 6 | 3 | 4 | 4 | 2 | 4 | 5 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 1 | 1 | 3 | 3 | 6 | 6 | 3 | 4 | 4 | 2 | 4 | 5 |
Baseline Characteristics
| Arm/Group Title | Schedule 1 Cohort 1 | Schedule 1 Cohort 2 | Schedule 1 Cohort 3 | Schedule 1 Cohort 5 | Schedule 1 Cohort 6 | Schedule 1 Cohort 7 | Schedule 2 Cohort 1 | Schedule 2 Cohort 2 | Schedule 2 Cohort 3 | Schedule 2 Cohort 4 | Schedule 2 Cohort 5 | Phase 2a Expansion Cohort | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | CRLX301 7.5 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 15 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 30 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 60 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 75 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 90 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 25 mg/m2 IV given weekly CRLX301 | CRLX301 35 mg/m2 IV given weekly CRLX301 | CRLX301 45 mg/m2 IV given weekly CRLX301 | CRLX301 54 mg/m2 IV given weekly CRLX301 | CRLX301 54 mg/m2 given weekly for 3 weeks with 1 week off CRLX301 | CRLX301 75mg/m2 IV given every 3 weeks CRLX301 | Total of all reporting groups |
| Overall Participants | 1 | 1 | 3 | 3 | 6 | 6 | 3 | 4 | 4 | 2 | 4 | 5 | 42 |
| Age (years) [Mean (Standard Deviation) ] | |||||||||||||
| Mean (Standard Deviation) [years] |
74
(NA)
|
43
(NA)
|
59
(19)
|
67.3
(1.53)
|
63.8
(9.79)
|
60.2
(11.62)
|
65
(2.65)
|
56
(11.52)
|
54
(12.25)
|
72.5
(2.12)
|
60.3
(3.1)
|
66.8
(4.15)
|
61.8
(10.2)
|
| Sex: Female, Male (Count of Participants) | |||||||||||||
| Female |
0
0%
|
0
0%
|
2
66.7%
|
1
33.3%
|
2
33.3%
|
4
66.7%
|
3
100%
|
1
25%
|
2
50%
|
0
0%
|
1
25%
|
0
0%
|
16
38.1%
|
| Male |
1
100%
|
1
100%
|
1
33.3%
|
2
66.7%
|
4
66.7%
|
2
33.3%
|
0
0%
|
3
75%
|
2
50%
|
2
100%
|
3
75%
|
5
100%
|
26
61.9%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||||||||
| Hispanic or Latino |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
2
40%
|
4
9.5%
|
| Not Hispanic or Latino |
1
100%
|
1
100%
|
2
66.7%
|
3
100%
|
6
100%
|
6
100%
|
3
100%
|
4
100%
|
3
75%
|
2
100%
|
4
100%
|
3
60%
|
38
90.5%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||||||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
1
25%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
3
7.1%
|
| White |
1
100%
|
1
100%
|
3
100%
|
3
100%
|
6
100%
|
4
66.7%
|
3
100%
|
3
75%
|
3
75%
|
1
50%
|
4
100%
|
5
100%
|
37
88.1%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
2
4.8%
|
| Primary Site of Disease at Study Entry (Count of Participants) | |||||||||||||
| Bladder |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
1
2.4%
|
| Bone |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
1
2.4%
|
| Breast |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
1
2.4%
|
| Hepatic/liver |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
3
50%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
4
9.5%
|
| Lung |
1
100%
|
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
3
7.1%
|
| Lymph nodes |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
20%
|
2
4.8%
|
| Pancreas |
0
0%
|
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
4.8%
|
| Pleura |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
2.4%
|
| Skin |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
2.4%
|
| Prostate |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
50%
|
1
25%
|
3
60%
|
5
11.9%
|
| Other (not specified) |
0
0%
|
1
100%
|
3
100%
|
0
0%
|
3
50%
|
1
16.7%
|
2
66.7%
|
3
75%
|
1
25%
|
0
0%
|
3
75%
|
1
20%
|
18
42.9%
|
| Abdomen/peritoneum |
0
0%
|
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
3
7.1%
|
| Baseline ECOG Status (Count of Participants) | |||||||||||||
| ECOG PS Score 0 |
0
0%
|
0
0%
|
2
66.7%
|
1
33.3%
|
4
66.7%
|
3
50%
|
1
33.3%
|
1
25%
|
3
75%
|
0
0%
|
1
25%
|
1
20%
|
17
40.5%
|
| ECOG PS Score 1 |
1
100%
|
1
100%
|
1
33.3%
|
2
66.7%
|
2
33.3%
|
3
50%
|
2
66.7%
|
3
75%
|
1
25%
|
2
100%
|
3
75%
|
4
80%
|
25
59.5%
|
| Baseline BMI (kg/m^2) (kg/m^2) [Mean (Standard Deviation) ] | |||||||||||||
| Mean (Standard Deviation) [kg/m^2] |
30.255
(NA)
|
19.63
(NA)
|
28.023
(1.2871)
|
26.917
(7.6956)
|
26.779
(4.8762)
|
27.422
(2.7810)
|
33.869
(5.5301)
|
25.173
(5.7256)
|
24.340
(3.1519)
|
28.142
(3.4551)
|
26.758
(4.9670)
|
29.118
(8.0521)
|
27.783
(3.2805)
|
Outcome Measures
| Title | Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities |
|---|---|
| Description | Determination of MTD is dependent upon number of dose limiting toxicities and significant adverse events observed. |
| Time Frame | 13 to 19 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The phase 1 safety population were analyzed for dose limiting toxicities and treatment emergent adverse events. Treatment totals include all patients that received the specific dose at any point during the study. |
| Arm/Group Title | Schedule 1 Cohort 1 | Schedule 1 Cohort 2 | Schedule 1 Cohort 3 | Schedule 1 Cohort 5 | Schedule 1 Cohort 6 | Schedule 1 Cohort 7 | Schedule 2 Cohort 1 | Schedule 2 Cohort 2 | Schedule 2 Cohort 3 | Schedule 2 Cohort 4 | Schedule 2 Cohort 5 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | CRLX301 7.5 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 15 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 30 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 60 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 75 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 90 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 25 mg/m2 IV given weekly CRLX301 | CRLX301 35 mg/m2 IV given weekly CRLX301 | CRLX301 45 mg/m2 IV given weekly CRLX301 | CRLX301 54 mg/m2 IV given weekly CRLX301 | CRLX301 54 mg/m2 given weekly for 3 weeks with 1 week off |
| Measure Participants | 1 | 1 | 3 | 3 | 6 | 6 | 3 | 4 | 4 | 2 | 4 |
| At least one TEAE |
1
|
1
|
3
|
3
|
6
|
6
|
3
|
4
|
4
|
2
|
4
|
| At least one Serious TEAE |
0
|
1
|
3
|
3
|
1
|
3
|
1
|
2
|
1
|
1
|
0
|
| At least one DLT |
0
|
0
|
0
|
0
|
0
|
2
|
0
|
0
|
0
|
0
|
0
|
| At least one severe TEAE |
0
|
1
|
3
|
3
|
4
|
6
|
0
|
2
|
2
|
2
|
4
|
| At least one related TEAE |
1
|
1
|
2
|
3
|
6
|
6
|
3
|
3
|
4
|
2
|
4
|
| At least one TEAE leading to discontinuation |
0
|
0
|
0
|
2
|
1
|
4
|
2
|
1
|
2
|
1
|
0
|
| Title | Number of Phase 2a Participants With Adverse Events as a Measure of Safety and Tolerability |
|---|---|
| Description | Safety variables will include AEs, SAEs, Severe AEs, Related AEs and AEs leading to Discontinuation in phase 2a subjects. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population (all patients) were analyzed for dose limiting toxicities and treatment emergent adverse events. Treatment totals include all patients that received the specific dose at any point during the study. |
| Arm/Group Title | Phase 2a Expansion Cohort |
|---|---|
| Arm/Group Description | CRLX301 75mg/m2 IV given every 3 weeks CRLX301 |
| Measure Participants | 5 |
| At least one TEAE |
5
|
| At least one Serious TEAE |
2
|
| At least one severe TEAE |
5
|
| At least one related TEAE |
5
|
| At least one TEAE leading to discontinuation |
2
|
| Title | Evaluate the Pharmacokinetic (PK) Profile of CRLX301 |
|---|---|
| Description | Area under the concentration vs time curve of released docetaxel in blood and/or urine specimens of patients receiving at least 1 dose of CRLX301. |
| Time Frame | 2.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Schedule 1 Cohort 1 | Schedule 1 Cohort 2 | Schedule 1 Cohort 3 | Schedule 1 Cohort 5 | Schedule 1 Cohort 6 | Schedule 1 Cohort 7 | Schedule 2 Cohort 1 | Schedule 2 Cohort 2 | Schedule 2 Cohort 3 | Schedule 2 Cohort 4 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | CRLX301 7.5 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 15 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 30 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 60 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 75 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 90 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 25 mg/m2 IV given weekly CRLX301 | CRLX301 35 mg/m2 IV given weekly CRLX301 | CRLX301 45 mg/m2 IV given weekly CRLX301 | CRLX301 54 mg/m2 IV given weekly CRLX301 |
| Measure Participants | 1 | 1 | 3 | 3 | 6 | 6 | 3 | 4 | 3 | 3 |
| Mean (Standard Deviation) [ng/ml*h] |
295
(0)
|
2197
(0)
|
1695
(438)
|
3783
(1054)
|
3613
(1054)
|
4639
(1561)
|
1433
(154)
|
2205
(731)
|
2019
(325)
|
2350
(453)
|
| Title | Percentage of Participants Stratified by Best Overall Tumor Response |
|---|---|
| Description | Best overall tumor response will be provided per dose cohort using RECIST 1.1 |
| Time Frame | 2.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients treated on study (safety population) were evaluated for overall tumor response. |
| Arm/Group Title | Schedule 1 Cohort 1 | Schedule 1 Cohort 2 | Schedule 1 Cohort 3 | Schedule 1 Cohort 5 | Schedule 1 Cohort 6 | Schedule 1 Cohort 7 | Schedule 2 Cohort 1 | Schedule 2 Cohort 2 | Schedule 2 Cohort 3 | Schedule 2 Cohort 4 | Schedule 2 Cohort 5 | Phase 2a Expansion Cohort |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | CRLX301 7.5 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 15 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 30 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 60 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 75 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 90 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 25 mg/m2 IV given weekly CRLX301 | CRLX301 35 mg/m2 IV given weekly CRLX301 | CRLX301 45 mg/m2 IV given weekly CRLX301 | CRLX301 54 mg/m2 IV given weekly CRLX301 | CRLX301 54 mg/m2 given weekly for 3 weeks with 1 week off CRLX301 | CRLX301 75mg/m2 IV given every 3 weeks CRLX301 |
| Measure Participants | 1 | 1 | 3 | 3 | 6 | 6 | 3 | 4 | 4 | 2 | 4 | 5 |
| Complete Response |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Partial Response |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
25
625%
|
0
0%
|
0
0%
|
20
400%
|
| Stable Disease |
0
0%
|
0
0%
|
66.7
2223.3%
|
100
3333.3%
|
16.7
278.3%
|
16.7
278.3%
|
100
3333.3%
|
75
1875%
|
50
1250%
|
50
2500%
|
100
2500%
|
40
800%
|
| Progressive Disease |
100
10000%
|
100
10000%
|
33.3
1110%
|
0
0%
|
66.7
1111.7%
|
16.7
278.3%
|
0
0%
|
25
625%
|
25
625%
|
50
2500%
|
0
0%
|
20
400%
|
| Not Evaluated |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | All AEs were collected occurring during the study period from the time of the first dose to the last day of the 30-day post-treatment follow-up period. | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||||||||||
| Arm/Group Title | Schedule 1 Cohort 1 | Schedule 1 Cohort 2 | Schedule 1 Cohort 3 | Schedule 1 Cohort 5 | Schedule 1 Cohort 6 | Schedule 1 Cohort 7 | Schedule 2 Cohort 1 | Schedule 2 Cohort 2 | Schedule 2 Cohort 3 | Schedule 2 Cohort 4 | Schedule 2 Cohort 5 | Phase 2a Expansion Cohort | ||||||||||||
| Arm/Group Description | CRLX301 7.5 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 15 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 30 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 60 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 75 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 90 mg/m2 IV given every 3 weeks CRLX301 | CRLX301 25 mg/m2 IV given weekly CRLX301 | CRLX301 35 mg/m2 IV given weekly CRLX301 | CRLX301 45 mg/m2 IV given weekly CRLX301 | CRLX301 54 mg/m2 IV given weekly CRLX301 | CRLX301 54 mg/m2 given weekly for 3 weeks with 1 week off CRLX301 | CRLX301 75mg/m2 IV given every 3 weeks CRLX301 | ||||||||||||
All Cause Mortality |
||||||||||||||||||||||||
| Schedule 1 Cohort 1 | Schedule 1 Cohort 2 | Schedule 1 Cohort 3 | Schedule 1 Cohort 5 | Schedule 1 Cohort 6 | Schedule 1 Cohort 7 | Schedule 2 Cohort 1 | Schedule 2 Cohort 2 | Schedule 2 Cohort 3 | Schedule 2 Cohort 4 | Schedule 2 Cohort 5 | Phase 2a Expansion Cohort | |||||||||||||
| 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 | Affected / at Risk (%) | # Events | |
| Total | 0/1 (0%) | 1/1 (100%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 2/4 (50%) | 0/4 (0%) | 0/2 (0%) | 0/4 (0%) | 1/5 (20%) | ||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||
| Schedule 1 Cohort 1 | Schedule 1 Cohort 2 | Schedule 1 Cohort 3 | Schedule 1 Cohort 5 | Schedule 1 Cohort 6 | Schedule 1 Cohort 7 | Schedule 2 Cohort 1 | Schedule 2 Cohort 2 | Schedule 2 Cohort 3 | Schedule 2 Cohort 4 | Schedule 2 Cohort 5 | Phase 2a Expansion Cohort | |||||||||||||
| 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 | Affected / at Risk (%) | # Events | |
| Total | 0/1 (0%) | 1/1 (100%) | 3/3 (100%) | 3/3 (100%) | 1/6 (16.7%) | 3/6 (50%) | 1/3 (33.3%) | 2/4 (50%) | 1/4 (25%) | 1/2 (50%) | 0/4 (0%) | 2/5 (40%) | ||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||
| Febrile neutropenia | /1 (NaN) | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | |
| Anaemia | /1 (NaN) | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | |
| Cardiac disorders | ||||||||||||||||||||||||
| Atrial fibrillation | /1 (NaN) | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/2 (50%) | 1 | 1/4 (25%) | 1 | 0/5 (0%) | 0 | |
| Gastrointestinal disorders | ||||||||||||||||||||||||
| Oesohageal stenosis | /1 (NaN) | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | |
| General disorders | ||||||||||||||||||||||||
| Pain | /1 (NaN) | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | |
| Pyrexia | /1 (NaN) | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | |
| Asthenia | /1 (NaN) | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | |
| Infections and infestations | ||||||||||||||||||||||||
| Injection site infection | /1 (NaN) | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | |
| Urinary tract infection | /1 (NaN) | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 2 | |
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||
| Fall | /1 (NaN) | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | |
| Infusion related reaction | /1 (NaN) | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | |
| Investigations | ||||||||||||||||||||||||
| Liver function test abnormal | /1 (NaN) | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | |
| Metabolism and nutrition disorders | ||||||||||||||||||||||||
| Failure to thrive | /1 (NaN) | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||
| Pain in extremity | /1 (NaN) | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | |
| Bone pain | /1 (NaN) | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | |
| Back pain | /1 (NaN) | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | |
| Nervous system disorders | ||||||||||||||||||||||||
| Peripheral motor neuropathy | /1 (NaN) | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | |
| Peripheral sensory neuropathy | /1 (NaN) | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | |
| Renal and urinary disorders | ||||||||||||||||||||||||
| Haematuria | /1 (NaN) | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||
| Pulmonary embolism | /1 (NaN) | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/2 (50%) | 1 | 1/4 (25%) | 1 | 0/5 (0%) | 0 | |
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||
| Schedule 1 Cohort 1 | Schedule 1 Cohort 2 | Schedule 1 Cohort 3 | Schedule 1 Cohort 5 | Schedule 1 Cohort 6 | Schedule 1 Cohort 7 | Schedule 2 Cohort 1 | Schedule 2 Cohort 2 | Schedule 2 Cohort 3 | Schedule 2 Cohort 4 | Schedule 2 Cohort 5 | Phase 2a Expansion Cohort | |||||||||||||
| 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 | Affected / at Risk (%) | # Events | |
| Total | 1/1 (100%) | 1/1 (100%) | 3/3 (100%) | 3/3 (100%) | 6/6 (100%) | 6/6 (100%) | 3/3 (100%) | 4/4 (100%) | 4/4 (100%) | 2/2 (100%) | 4/4 (100%) | 5/5 (100%) | ||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||
| Agranulocytosis | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 |
| Anaemia | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 2/6 (33.3%) | 3 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 2/4 (50%) | 5 | 2/4 (50%) | 3 | 2/2 (100%) | 2 | 1/4 (25%) | 4 | 2/5 (40%) | 3 |
| Febrile neutropenia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Leukopenia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 2 |
| Leukocytosis | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 2/4 (50%) | 3 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Neutropenia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 4 | 0/3 (0%) | 0 | 3/6 (50%) | 12 | 1/6 (16.7%) | 3 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 1/2 (50%) | 1 | 2/4 (50%) | 3 | 5/5 (100%) | 6 |
| Thrombocytopenia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||||||||||
| Atrial fibrillation | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 1/2 (50%) | 2 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Cardiac failure | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 1/2 (50%) | 2 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Palpitations | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Pericardial effusion | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 |
| Sinus tachycardia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 1/2 (50%) | 1 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Tachycardia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||||||||||||||||
| Ear pain | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Eye disorders | ||||||||||||||||||||||||
| Blepharitis | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 3/4 (75%) | 3 | 0/5 (0%) | 0 |
| Dry eye | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 0/2 (0%) | 0 | 1/4 (25%) | 2 | 0/5 (0%) | 0 |
| Episcleritis | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Eye disorder | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Lacrimation increased | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 2/4 (50%) | 2 | 0/2 (0%) | 0 | 2/4 (50%) | 4 | 0/5 (0%) | 0 |
| Visual impairment | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||||||||
| Abdominal distention | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Abdominal pain | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 2/3 (66.7%) | 2 | 1/3 (33.3%) | 2 | 3/6 (50%) | 3 | 1/6 (16.7%) | 1 | 2/3 (66.7%) | 2 | 1/4 (25%) | 2 | 1/4 (25%) | 4 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Abdominal pain lower | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Abdominal pain upper | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Chapped lips | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Cheilitis | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 3 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Constipation | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 2/3 (66.7%) | 4 | 0/3 (0%) | 0 | 2/6 (33.3%) | 3 | 1/6 (16.7%) | 1 | 1/3 (33.3%) | 4 | 2/4 (50%) | 2 | 2/4 (50%) | 3 | 2/2 (100%) | 5 | 0/4 (0%) | 0 | 1/5 (20%) | 1 |
| Diarrhoea | 1/1 (100%) | 1 | 1/1 (100%) | 2 | 2/3 (66.7%) | 3 | 3/3 (100%) | 3 | 3/6 (50%) | 3 | 0/6 (0%) | 0 | 2/3 (66.7%) | 3 | 2/4 (50%) | 4 | 2/4 (50%) | 6 | 1/2 (50%) | 1 | 1/4 (25%) | 1 | 1/5 (20%) | 1 |
| Dry mouth | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Dyspepsia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/3 (33.3%) | 3 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Dysphagia | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Flatulence | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Gastrooesophageal reflux disease | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 2/3 (66.7%) | 4 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 3 | 0/3 (0%) | 0 | 2/4 (50%) | 2 | 1/4 (25%) | 1 | 1/2 (50%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Glossodynia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Haemorrhoids | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Mouth ulceration | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Nausea | 0/1 (0%) | 0 | 1/1 (100%) | 2 | 1/3 (33.3%) | 2 | 2/3 (66.7%) | 2 | 2/6 (33.3%) | 3 | 1/6 (16.7%) | 1 | 2/3 (66.7%) | 2 | 0/4 (0%) | 0 | 3/4 (75%) | 5 | 2/2 (100%) | 2 | 3/4 (75%) | 7 | 1/5 (20%) | 1 |
| Oral pain | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Oesophageal stenosis | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Paraesthesia oral | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Proctalgia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Salivary hypersecretion | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Stomatitis | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Vomiting | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 4 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 2/4 (50%) | 2 | 1/2 (50%) | 1 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| General disorders | ||||||||||||||||||||||||
| Asthenia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Extravasation | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Chest pain | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Chills | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Fatigue | 1/1 (100%) | 1 | 1/1 (100%) | 1 | 1/3 (33.3%) | 3 | 3/3 (100%) | 8 | 5/6 (83.3%) | 6 | 4/6 (66.7%) | 9 | 2/3 (66.7%) | 3 | 3/4 (75%) | 5 | 4/4 (100%) | 10 | 2/2 (100%) | 5 | 4/4 (100%) | 10 | 3/5 (60%) | 4 |
| Gait disturbance | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 1/4 (25%) | 2 | 0/5 (0%) | 0 |
| Influenza like illness | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Localised oedema | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 0/2 (0%) | 0 | 1/4 (25%) | 2 | 0/5 (0%) | 0 |
| Malaise | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 0/2 (0%) | 0 | 1/4 (25%) | 2 | 0/5 (0%) | 0 |
| Mucosal inflammation | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/3 (66.7%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Non-cardiac chest pain | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Oedema peripheral | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 2/4 (50%) | 3 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 1/5 (20%) | 2 |
| Pain | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Peripheral swelling | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 2 |
| Pyrexia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 2/3 (66.7%) | 2 | 1/3 (33.3%) | 3 | 1/6 (16.7%) | 1 | 3/6 (50%) | 3 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||||||||||||||
| Jaundice | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| candida infection | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Infections and infestations | ||||||||||||||||||||||||
| conjunctivitis | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 2/4 (50%) | 2 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Cystitis | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Hordeolum | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Injection site infection | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Lower respiratory tract infection | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Lung infection | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Oral candidiasis | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Sinusitis | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 2 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Skin infection | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Upper respiratory tract infection | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Urinary tract infection | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 5 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 3/4 (75%) | 3 | 1/4 (25%) | 2 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 3 |
| Viral infection | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||
| Fall | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 2/4 (50%) | 3 | 1/2 (50%) | 1 | 2/4 (50%) | 3 | 0/5 (0%) | 0 |
| Infusion related reaction | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 3 | 1/3 (33.3%) | 1 | 4/6 (66.7%) | 5 | 2/6 (33.3%) | 3 | 2/3 (66.7%) | 4 | 1/4 (25%) | 2 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 1/5 (20%) | 1 |
| Thermal burn | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Investigations | ||||||||||||||||||||||||
| Alanine aminotransferase increased | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Aspartate aminotransferase increased | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 1/4 (25%) | 2 | 1/2 (50%) | 2 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Blood alkaline phosphatase increased | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 2 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Blood bilirubin increased | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 3 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 |
| Blood cholesterol incrased | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Blood creatinine increased | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 1/5 (20%) | 1 |
| Blood triglycerides increased | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 2/5 (40%) | 2 |
| Electrocardiogram | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Electrocardiogram QT prolonged | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Electrocardiogram abnormal | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/2 (50%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Liver function test abnormal | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Lymphocyte count decreased | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Neutrophil count decreased | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 0/2 (0%) | 0 | 2/4 (50%) | 5 | 0/5 (0%) | 0 |
| Reticulocyte count increased | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Urine output decreased | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Waist circumference increased | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 2 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Weight decreased | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| White blood cell count decreased | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 2/4 (50%) | 4 | 0/2 (0%) | 0 | 2/4 (50%) | 3 | 0/5 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||||||||||
| Decreased appetite | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 3/3 (100%) | 3 | 1/6 (16.7%) | 2 | 5/6 (83.3%) | 7 | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 4/4 (100%) | 9 | 2/2 (100%) | 6 | 2/4 (50%) | 3 | 0/5 (0%) | 0 |
| Dehydration | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 3 | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 1/4 (25%) | 3 | 1/2 (50%) | 3 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Failure to thrive | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Gout | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Hypercalcaemia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Hyperglycaemia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 4 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 |
| Hyperkalaemia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 4 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Hyperphosphataemia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Hypertriglyceridaemia | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Hyperuricaemia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 |
| Hypocalcaemia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Hypoglycaemia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 3 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Hypokalaemia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 1/6 (16.7%) | 3 | 1/6 (16.7%) | 1 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 |
| Hypomagnesaemia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/2 (50%) | 1 | 0/4 (0%) | 0 | 2/5 (40%) | 2 |
| Hyponatraemia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 3 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 2/4 (50%) | 4 | 1/5 (20%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||
| Arthralgia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 | 3/6 (50%) | 4 | 2/6 (33.3%) | 6 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 1/2 (50%) | 1 | 2/4 (50%) | 3 | 1/5 (20%) | 2 |
| Back pain | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 2 | 2/6 (33.3%) | 2 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 2/4 (50%) | 2 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 1/5 (20%) | 1 |
| Bone pain | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Joint swelling | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Muscular weakness | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 1/2 (50%) | 3 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Musculoskeletal chest pain | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Musculoskeletal pain | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 1/5 (20%) | 1 |
| Myalgia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 2 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Myopathy | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Pain in extremity | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||
| Cancer pain | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 2/5 (40%) | 2 |
| Seborrhoeic keratosis | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Tumour pain | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 3 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||||||||||
| cognitive disorder | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 1/4 (25%) | 9 | 0/5 (0%) | 0 |
| Dizziness | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 2/4 (50%) | 2 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Dysgeusia | 1/1 (100%) | 1 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 3 | 2/6 (33.3%) | 3 | 4/6 (66.7%) | 4 | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 4/4 (100%) | 7 | 2/2 (100%) | 3 | 3/4 (75%) | 4 | 0/5 (0%) | 0 |
| Headache | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 2/6 (33.3%) | 3 | 0/6 (0%) | 0 | 2/3 (66.7%) | 3 | 1/4 (25%) | 1 | 2/4 (50%) | 3 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Hypoaesthesia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 |
| Lethargy | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Neuropathy peripheral | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 2 | 0/6 (0%) | 0 | 2/6 (33.3%) | 3 | 0/3 (0%) | 0 | 2/4 (50%) | 3 | 3/4 (75%) | 8 | 1/2 (50%) | 2 | 2/4 (50%) | 5 | 2/5 (40%) | 5 |
| Paraesthesia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 4/6 (66.7%) | 4 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Peripheral motor neuropathy | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Peripheral sensory neuropathy | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 2/6 (33.3%) | 3 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 2/4 (50%) | 4 | 0/2 (0%) | 0 | 3/4 (75%) | 7 | 0/5 (0%) | 0 |
| Presyncope | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/2 (50%) | 1 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Restless legs syndrome | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Sciatica | 1/1 (100%) | 2 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||||||||||
| Agitation | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Anxiety | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Insomnia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 3 | 1/3 (33.3%) | 1 | 2/4 (50%) | 2 | 1/4 (25%) | 2 | 1/2 (50%) | 2 | 2/4 (50%) | 3 | 0/5 (0%) | 0 |
| Sleep disorder | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 2/4 (50%) | 3 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||||||||||
| Haematuria | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 |
| Micturition urgency | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 |
| Urinary incontinence | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||||||||||
| pelvic pain | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 1/4 (25%) | 2 | 0/5 (0%) | 0 |
| Vaginal haemorrhage | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||
| Cough | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 2/4 (50%) | 2 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Dyspnoea | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 1/3 (33.3%) | 2 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 1/3 (33.3%) | 2 | 1/4 (25%) | 1 | 2/4 (50%) | 4 | 1/2 (50%) | 5 | 1/4 (25%) | 2 | 1/5 (20%) | 1 |
| Dyspnoea exertional | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Epistaxis | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/3 (33.3%) | 2 | 2/4 (50%) | 3 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Nasal congestion | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 1/2 (50%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Oropharyngeal pain | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Pleural effusion | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 1/2 (50%) | 1 | 0/4 (0%) | 0 | 1/5 (20%) | 1 |
| Pneumonitis | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Productive cough | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Pulmonary embolism | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Rhinitis allergic | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Rhinorrhoea | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Sinus disorder | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||
| Alopecia | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 3 | 2/3 (66.7%) | 2 | 1/4 (25%) | 1 | 2/4 (50%) | 3 | 0/2 (0%) | 0 | 2/4 (50%) | 2 | 0/5 (0%) | 0 |
| Erythema | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 2 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Nail bed tenderness | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Nail disorder | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Nail ridging | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Nail toxicity | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Night sweats | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Pain of skin | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Palmar-plantar erythrodysaesthesia syndrome | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Pruritus | 0/1 (0%) | 0 | 1/1 (100%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Rash | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Rash erythematous | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Rash maculo-papular | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Skin hyperpigmenation | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Vitiligo | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Vascular disorders | ||||||||||||||||||||||||
| Flushing | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 2/3 (66.7%) | 6 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Haematoma | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Hot flush | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Hypertension | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Hypotension | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 |
| Orthostatic hypotension | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
| Thrombophlebitis | 0/1 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 4 | 0/4 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Manager, Clinical Operations |
|---|---|
| Organization | NewLink Genetics Corporation |
| Phone | 515-598-5020 ext 2624 |
| csmith@linkp.com |
Responsible Party:
NewLink Genetics Corporation
ClinicalTrials.gov Identifier:
NCT02380677
Other Study ID Numbers:
- CRLX301-101
First Posted:
Mar 5, 2015
Last Update Posted:
Jun 9, 2020
Last Verified:
May 1, 2020