Open-Label Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies
Sponsor
Incyte Corporation (Industry)
Overall Status
Terminated
CT.gov ID
NCT02711137
Collaborator
(none)
137
18
14
32.9
7.6
0.2
Study Details
Study Description
Brief Summary
The purpose of the Study is to select a dose and assess the safety and tolerability of INCB057643 as a monotherapy (Part 1 and Part 2) and in combination with standard-of-care (SOC) agents (Part 3 and Part 4) for subjects with advanced malignancies.
Part 1 will determine the maximum tolerated dose of INCB057643 and/or a tolerated dose that demonstrates sufficient pharmacologic activity. Part 2 will further evaluate the safety, preliminary efficacy, PK, and PD of the dose(s) selected in Part 1 in select tumor types including solid tumors, lymphomas and other hematologic malignancies. Part 3 will determine the tolerated dose of INCB057643 in combination with select SOC agents; and assess the safety and tolerability of the combination therapy in select advanced solid tumors and hematologic malignancies. Part 4 will further evaluate the safety, preliminary efficacy, PK, and PD of the selected dose combination from Part 3 in 4 specific advanced solid tumor and hematologic malignancies.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
137 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/Dose-Expansion, Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies
Actual Study Start Date
:
May 18, 2016
Actual Primary Completion Date
:
Feb 13, 2019
Actual Study Completion Date
:
Feb 13, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part1/Treatment Group A : 8mg QD INCB057643 Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma |
Drug: INCB057643
Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).
|
| Experimental: Part1/Treatment Group A : 12mg QD INCB057643 Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma |
Drug: INCB057643
Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).
|
| Experimental: Part1/Treatment Group A : 16mg QD INCB057643 Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma |
Drug: INCB057643
Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).
|
| Experimental: Part1/Treatment Group B : 8mg QD INCB057643 Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group B (TGB), based on protocol-specific criteria. Treatment Group B included any acute leukemia, HRMDS, MDS/MPN, or MF |
Drug: INCB057643
Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).
|
| Experimental: Part1/Treatment Group B : 12mg QD INCB057643 Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group B (TGB), based on protocol-specific criteria. Treatment Group B included any acute leukemia, HRMDS, MDS/MPN, or MF. |
Drug: INCB057643
Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).
|
| Experimental: Part1/Treatment Group C : 8mg QD INCB057643 Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group C (TGC), based on protocol-specific criteria. Treatment Group C includes subjects with MM |
Drug: INCB057643
Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).
|
| Experimental: Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort Initial cohort dose of INCB054763 monotherapy at the specified RP2D dose selected in Part 1 cohort escalation treatment group A (TGA), based on protocol-specific criteria. Part 2 Treatment Group A expansion included pancreatic adenocarcinoma, castration-resistant prostrate cancer, breast cancer, high grade serious ovarian cancer, glioblastoma multiform, non-hodgkin's lymphoma, ewing's sarcoma, and solid tumor or lymphoma. |
Drug: INCB057643
Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).
|
| Experimental: Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort Initial cohort dose of INCB057463 monotherapy at the specified RP2D dose selected in Part 1 cohort escalation treatment group B (TGB), based on protocol-specific criteria. Part 2 Treatment Group B expansion included pancreatic adenocarcinoma, castration-resistant prostrate cancer, breast cancer, high grade serious ovarian cancer, glioblastoma multiform, non-hodgkin's lymphoma, ewing's sarcoma, and solid tumor or lymphoma. |
Drug: INCB057643
Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).
|
| Experimental: Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg Initial cohort dose of INCB057643 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Gemcitabine) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies where Gemcitabine is relevant |
Drug: INCB057643
Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).
Drug: Gemcitabine
Standard of Care (SOC) agents
|
| Experimental: Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Paclitaxel) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies. |
Drug: INCB057643
Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).
Drug: Paclitaxel
Standard of Care (SOC) agents
|
| Experimental: Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Rucaparib) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies. |
Drug: INCB057643
Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).
Drug: Rucaparib
Standard of Care (SOC) agents
|
| Experimental: Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Abiraterone + Prednisone) in Castration Resistant Prostrate Cancer |
Drug: INCB057643
Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).
Drug: Abiraterone
Standard of Care (SOC) agents
|
| Experimental: Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Ruxolitinib) in Myelofibrosis. |
Drug: INCB057643
Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).
Drug: Ruxolitinib
Standard of Care (SOC) agents
|
| Experimental: Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Azacitidine) in Acute Myeloid Leukemia and Myelodysplastic Syndrome |
Drug: INCB057643
Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).
Drug: Azacitidine
Standard of Care (SOC) agents
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Treatment Emergent Adverse Events (TEAE's). [From screening through at least 30 days after end of treatment, up to approximately 24 months]
Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.
Secondary Outcome Measures
- Percent Inhibition of Total Cellular Myc Protein Concentrations Before and After Administration of INCB057643 When Administered as Monotherapy in an Ex-vivo Assay [PD in plasma at pre-dose and 0.5, 1, 2, 4, 6 and 8 hours postdose, for C1D1 and C1D8, and 24hrs post dose for C1D1]
An ex vivo assay (utilized in monotherapy only), Measuring Total c-Myc protein expressed from an exogenously added cell line (KMS12BM) to patient plasma, before and after administration of INCB057643.
- Objective Response Rate (ORR) With INCB057643 in Solid Tumors [Efficacy measures from screening through end of treatment and follow-up (every 9 weeks), up to approximately 24 months]
Objective response rate is defined as the proportion of subjects who have an objective response using the applicable disease assessment criteria. ORR was proportion of participants with best overall response [complete response (CR) or partial response (PR)].
- Cmax: Maximum Observed Plasma Concentration of INCB057643. [Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1 and C1D8]
Maximum Observed Plasma Concentration INCB057643 administered as monotherapy in fasted state.
- Tmax: Time to Maximum Plasma Concentration of INCB057643 [Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1 and C1D8]
Time to maximum plasma concentration of INCB057643 administered as monotherapy in fasted state
- AUC0-t: Area Under the Single-dose Plasma Concentration-time Curve of INCB057643 [Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1]
Area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration of INCB057643 administered as monotherapy in fasted state
- AUC0-24: Area Under the Steady-state Plasma Concentration-time Curve of INCB057643 Administered as Monotherapy [Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D8]
Area under the steady-state plasma concentration-time curve over 1 dosing interval from Hour 0 to 24 for QD administration of INCB057643 administered as monotherapy in fasted state
- Part 2 - Cmax: Maximum Observed Plasma Concentration of INCB057643. [C2D1]
Maximum Observed Plasma Concentration INCB057643 administered as monotherapy in fed state.
- Part 2-Tmax: Time to Maximum Plasma Concentration of INCB057643 [C2D1]
Time to maximum plasma concentration of INCB057643 administered as monotherapy in fed state
- AUC0-24: Area Under the Steady-state Plasma Concentration-time Curve of INCB057643 Administered as Monotherapy [C2D1]
Area under the steady-state plasma concentration-time curve over 1 dosing interval from Hour 0 to 24 for QD administration of INCB057643 administered as monotherapy in fed state.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Histologically or cytologically confirmed diagnosis of relapsed or refractory advanced or metastatic malignancies:
-
Part 1: solid tumors or lymphomas, or hematologic malignancies
-
Part 2: histologically confirmed disease in specific tumor types
-
Part 3: advanced solid tumor or hematologic malignancy
-
Part 4: select advanced solid tumor or hematologic malignancy
-
For Part 1 and 2, subjects must have progressed following at least 1 line of prior therapy and there is no further established therapy that is known to provide clinical benefit (including subjects who are intolerant to the established therapy)
-
For Parts 3 and 4, subjects must have progressed following at least 1 line of prior therapy, and the treatment with the select SOC agent is relevant for the specific disease cohort.
-
Life expectancy > 12 weeks, for MF subjects in Parts 3 and 4, life expectancy > 24 weeks
-
Eastern Cooperative Oncology Group (ECOG) performance status
-
Parts 1 and 3: 0 or 1
-
Parts 2 and 4: 0, 1, or 2
-
Willingness to avoid pregnancy or fathering children
Exclusion Criteria:
-
Inadequate bone marrow function per protocol-specified hemoglobin, platelet count, and absolute neutrophil count
-
Inadequate organ function per protocol-specified total bilirubin, AST and ALT, creatinine clearance and alkaline phosphatase.
-
Receipt of anticancer medications or investigational drugs within protocol-specified intervals
-
Unless approved by the medical monitor, may not have received an allogeneic hematopoietic stem cell transplant within 6 months before treatment, or have active graft-versus-host-disease following allogeneic transplant
-
Unless approved by the medical monitor, may not have received autologous hematopoietic stem cell transplant within 3 months before treatment
-
Any unresolved toxicity ≥ Grade 2 (except stable Grade 2 peripheral neuropathy or alopecia) from previous anticancer therapy
-
Radiotherapy within the 2 weeks before initiation of treatment. Palliative radiation treatment to nonindex or bone lesions performed less than 2 weeks before treatment initiation may be considered with medical monitor approval
-
Currently active and uncontrolled infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment
-
Untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed
-
History or presence of abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful
-
Type 1 diabetes or uncontrolled Type 2 diabetes
-
HbA1c of ≥ 8% (all subjects will have HbA1c test at screening)
-
Any sign of clinically significant bleeding
-
Coagulation panel within protocol-specified parameters
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama | Birmingham | Alabama | United States | 35294-3300 |
| 2 | University of California | La Jolla | California | United States | 92093 |
| 3 | Sarah Cannon Research Institute at Health One | Denver | Colorado | United States | 80218 |
| 4 | Yale University | New Haven | Connecticut | United States | 06510 |
| 5 | Sylvester Comprehensive Cancer Center | Miami | Florida | United States | 33136 |
| 6 | Hematology - Oncology Associates of Treasure Coast | Port Saint Lucie | Florida | United States | 34952 |
| 7 | University of Michigan | Ann Arbor | Michigan | United States | 48109 |
| 8 | University of Minnesota | Minneapolis | Minnesota | United States | 55455 |
| 9 | Washington University | Saint Louis | Missouri | United States | 63110 |
| 10 | University of Rochester, Wilmot Cancer Center | Rochester | New York | United States | 14642 |
| 11 | University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | United States | 27599 |
| 12 | Wake Forest Baptist Health | Winston-Salem | North Carolina | United States | 27157 |
| 13 | Oncology Consultants, P.A. | Houston | Texas | United States | 77030 |
| 14 | The Methodist Hospital | Houston | Texas | United States | 77030 |
| 15 | Huntsman Cancer Institute | Salt Lake City | Utah | United States | 84112 |
| 16 | MultiCare Institute for Research and Innovation | Tacoma | Washington | United States | 98405 |
| 17 | Institut Jules Bordet, Clinical Trial Conduct Unit | Brussels | Belgium | B-1000 | |
| 18 | HÔPITAL SAINT-LOUIS, Service Hématologie Adultes | Paris | France | 75010 |
Sponsors and Collaborators
- Incyte Corporation
Investigators
- Study Director: Fred Zheng, MD, PhD, Incyte Corporation
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT02711137
Other Study ID Numbers:
- INCB 57643-101
First Posted:
Mar 17, 2016
Last Update Posted:
Apr 28, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Incyte Corporation
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | A total of 137 subjects enrolled at 19 different sites in USA. |
|---|---|
| Pre-assignment Detail | Subjects were assigned to either dose escalation/dose-expansion study of INCB057643 as monotherapy or in combination with SOC agents in subjects with relapsing or refractory malignancies. |
| Arm/Group Title | Part1/Treatment Group A : 8mg QD INCB057643 | Part1/Treatment Group A : 12mg QD INCB057643 | Part1/Treatment Group A : 16mg QD INCB057643 | Part1/Treatment Group B : 8mg QD INCB057643 | Part1/Treatment Group B : 12mg QD INCB057643 | Part1/Treatment Group C : 8mg QD INCB057643 | Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort | Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort | Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg | Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg | Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg | Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni | Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg | Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg | Enrolled But Not Dosed |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma | Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group B (TGB), based on protocol-specific criteria. Treatment Group B included any acute leukemia, HRMDS, MDS/MPN, or MF | Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group B (TGB), based on protocol-specific criteria. Treatment Group B included any acute leukemia, HRMDS, MDS/MPN, or MF. | Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group C (TGC), based on protocol-specific criteria. Treatment Group C includes subjects with MM | Initial cohort dose of INCB054763 monotherapy at the specified RP2D dose selected in Part 1 cohort escalation treatment group A (TGA), based on protocol-specific criteria. Part 2 Treatment Group A expansion included pancreatic adenocarcinoma, castration-resistant prostrate cancer, breast cancer, high grade serious ovarian cancer, glioblastoma multiform, non-hodgkin's lymphoma, ewing's sarcoma, and solid tumor or lymphoma. | Initial cohort dose of INCB057463 monotherapy at the specified RP2D dose selected in Part 1 cohort escalation treatment group B (TGB), based on protocol-specific criteria. Part 2 Treatment Group B expansion included pancreatic adenocarcinoma, castration-resistant prostrate cancer, breast cancer, high grade serious ovarian cancer, glioblastoma multiform, non-hodgkin's lymphoma, ewing's sarcoma, and solid tumor or lymphoma. | Initial cohort dose of INCB057643 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Gemcitabine) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies where Gemcitabine is relevant | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Paclitaxel) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies. | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Rucaparib) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies. | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Abiraterone + Prednisone) in Castration Resistant Prostrate Cancer | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Ruxolitinib) in Myelofibrosis. | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Azacitidine) in Acute Myeloid Leukemia and Myelodysplastic Syndrome | 3 participants enrolled in the study and discontinued the study before study drug is administered |
| Period Title: Overall Study | |||||||||||||||
| STARTED | 4 | 5 | 8 | 7 | 5 | 1 | 86 | 5 | 1 | 2 | 4 | 3 | 1 | 2 | 3 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 4 | 5 | 8 | 7 | 5 | 1 | 86 | 5 | 1 | 2 | 4 | 3 | 1 | 2 | 3 |
Baseline Characteristics
| Arm/Group Title | Part1/Treatment Group A : 8mg QD INCB057643 | Part1/Treatment Group A : 12mg QD INCB057643 | Part1/Treatment Group A : 16mg QD INCB057643 | Part1/Treatment Group B : 8mg QD INCB057643 | Part1/Treatment Group B : 12mg QD INCB057643 | Part1/Treatment Group C : 8mg QD INCB057643 | Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort | Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort | Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg | Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg | Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg | Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni | Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg | Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg | Enrolled But Not Dosed | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma | Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group B (TGB), based on protocol-specific criteria. Treatment Group B included any acute leukemia, HRMDS, MDS/MPN, or MF | Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group B (TGB), based on protocol-specific criteria. Treatment Group B included any acute leukemia, HRMDS, MDS/MPN, or MF. | Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group C (TGC), based on protocol-specific criteria. Treatment Group C includes subjects with MM | Initial cohort dose of INCB054763 monotherapy at the specified RP2D dose selected in Part 1 cohort escalation treatment group A (TGA), based on protocol-specific criteria. Part 2 Treatment Group A expansion included pancreatic adenocarcinoma, castration-resistant prostrate cancer, breast cancer, high grade serious ovarian cancer, glioblastoma multiform, non-hodgkin's lymphoma, ewing's sarcoma, and solid tumor or lymphoma. | Initial cohort dose of INCB057463 monotherapy at the specified RP2D dose selected in Part 1 cohort escalation treatment group B (TGB), based on protocol-specific criteria. Part 2 Treatment Group B expansion included pancreatic adenocarcinoma, castration-resistant prostrate cancer, breast cancer, high grade serious ovarian cancer, glioblastoma multiform, non-hodgkin's lymphoma, ewing's sarcoma, and solid tumor or lymphoma. | Initial cohort dose of INCB057643 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Gemcitabine) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies where Gemcitabine is relevant | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Paclitaxel) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies. | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Rucaparib) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies. | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Abiraterone + Prednisone) in Castration Resistant Prostrate Cancer | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Ruxolitinib) in Myelofibrosis. | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Azacitidine) in Acute Myeloid Leukemia and Myelodysplastic Syndrome | 3 participants enrolled in the study and discontinued the study before study drug is administered | Total of all reporting groups |
| Overall Participants | 4 | 5 | 8 | 7 | 5 | 1 | 86 | 5 | 1 | 2 | 4 | 3 | 1 | 2 | 3 | 137 |
| Age (Years) [Mean (Standard Deviation) ] | ||||||||||||||||
| Mean (Standard Deviation) [Years] |
64.3
(10.21)
|
60.2
(12.26)
|
60.5
(11.44)
|
68.9
(5.81)
|
75.8
(7.33)
|
70.0
(NA)
|
60.6
(13.80)
|
72.6
(10.92)
|
72.0
(0)
|
56.0
(12.73)
|
66.0
(6.16)
|
67.7
(4.04)
|
75.0
(0)
|
76.5
(2.12)
|
66.0
(6.24)
|
63.0
(12.80)
|
| Sex: Female, Male (Count of Participants) | ||||||||||||||||
| Female |
2
50%
|
2
40%
|
5
62.5%
|
3
42.9%
|
1
20%
|
0
0%
|
48
55.8%
|
0
0%
|
1
100%
|
1
50%
|
4
100%
|
0
0%
|
0
0%
|
0
0%
|
1
33.3%
|
68
49.6%
|
| Male |
2
50%
|
3
60%
|
3
37.5%
|
4
57.1%
|
4
80%
|
1
100%
|
38
44.2%
|
5
100%
|
0
0%
|
1
50%
|
0
0%
|
3
100%
|
1
100%
|
2
100%
|
2
66.7%
|
69
50.4%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||||||||||||||
| White/Caucasian |
3
75%
|
3
60%
|
5
62.5%
|
6
85.7%
|
4
80%
|
0
0%
|
71
82.6%
|
5
100%
|
0
0%
|
1
50%
|
4
100%
|
3
100%
|
1
100%
|
2
100%
|
3
100%
|
111
81%
|
| Black/African American |
1
25%
|
0
0%
|
2
25%
|
1
14.3%
|
0
0%
|
0
0%
|
10
11.6%
|
0
0%
|
1
100%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
16
11.7%
|
| 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%
|
0
0%
|
0
0%
|
0
0%
|
| American-Indian/Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.2%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.7%
|
| Native Hawaiian/Pacific Islander |
0
0%
|
1
20%
|
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%
|
1
0.7%
|
| Other |
0
0%
|
1
20%
|
1
12.5%
|
0
0%
|
1
20%
|
1
100%
|
2
2.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
6
4.4%
|
| Missing |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.2%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.7%
|
Outcome Measures
| Title | Number of Participants With Treatment Emergent Adverse Events (TEAE's). |
|---|---|
| Description | Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment. |
| Time Frame | From screening through at least 30 days after end of treatment, up to approximately 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants enrolled in the study who received at least 1 dose of study drug. |
| Arm/Group Title | Part1/Treatment Group A : 8mg QD INCB057643 | Part1/Treatment Group A : 12mg QD INCB057643 | Part1/Treatment Group A : 16mg QD INCB057643 | Part1/Treatment Group B : 8mg QD INCB057643 | Part1/Treatment Group B : 12mg QD INCB057643 | Part1/Treatment Group C : 8mg QD INCB057643 | Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort | Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort | Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg | Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg | Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg | Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni | Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg | Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma | Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group B (TGB), based on protocol-specific criteria. Treatment Group B included any acute leukemia, HRMDS, MDS/MPN, or MF | Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group B (TGB), based on protocol-specific criteria. Treatment Group B included any acute leukemia, HRMDS, MDS/MPN, or MF. | Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group C (TGC), based on protocol-specific criteria. Treatment Group C includes subjects with MM | Initial cohort dose of INCB054763 monotherapy at the specified RP2D dose selected in Part 1 cohort escalation treatment group A (TGA), based on protocol-specific criteria. Part 2 Treatment Group A expansion included pancreatic adenocarcinoma, castration-resistant prostrate cancer, breast cancer, high grade serious ovarian cancer, glioblastoma multiform, non-hodgkin's lymphoma, ewing's sarcoma, and solid tumor or lymphoma. | Initial cohort dose of INCB057463 monotherapy at the specified RP2D dose selected in Part 1 cohort escalation treatment group B (TGB), based on protocol-specific criteria. Part 2 Treatment Group B expansion included pancreatic adenocarcinoma, castration-resistant prostrate cancer, breast cancer, high grade serious ovarian cancer, glioblastoma multiform, non-hodgkin's lymphoma, ewing's sarcoma, and solid tumor or lymphoma. | Initial cohort dose of INCB057643 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Gemcitabine) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies where Gemcitabine is relevant | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Paclitaxel) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies. | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Rucaparib) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies. | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Abiraterone + Prednisone) in Castration Resistant Prostrate Cancer | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Ruxolitinib) in Myelofibrosis. | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Azacitidine) in Acute Myeloid Leukemia and Myelodysplastic Syndrome |
| Measure Participants | 4 | 5 | 8 | 7 | 5 | 1 | 86 | 5 | 1 | 2 | 4 | 3 | 1 | 2 |
| Number [Participants] |
4
100%
|
5
100%
|
8
100%
|
7
100%
|
5
100%
|
1
100%
|
86
100%
|
5
100%
|
1
100%
|
2
100%
|
4
100%
|
3
100%
|
1
100%
|
2
100%
|
| Title | Percent Inhibition of Total Cellular Myc Protein Concentrations Before and After Administration of INCB057643 When Administered as Monotherapy in an Ex-vivo Assay |
|---|---|
| Description | An ex vivo assay (utilized in monotherapy only), Measuring Total c-Myc protein expressed from an exogenously added cell line (KMS12BM) to patient plasma, before and after administration of INCB057643. |
| Time Frame | PD in plasma at pre-dose and 0.5, 1, 2, 4, 6 and 8 hours postdose, for C1D1 and C1D8, and 24hrs post dose for C1D1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | 8mg QD INCB057643 | 12mg QD INCB057643 | 16mg QD INCB057643 |
|---|---|---|---|
| Arm/Group Description | cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the Part 1 TGA,TGB,TGC. | 12mg QD INCB057643 Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the Part 1 TGA,TGB, and Part 2 TGA,TGB. | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the Part 1 TGA |
| Measure Participants | 11 | 51 | 7 |
| C1D1 |
24
(199.5)
|
28
(200.1)
|
54
(236.3)
|
| C1D8 |
30
(42.59)
|
43.4
(52.7)
|
65
(55.21)
|
| Title | Objective Response Rate (ORR) With INCB057643 in Solid Tumors |
|---|---|
| Description | Objective response rate is defined as the proportion of subjects who have an objective response using the applicable disease assessment criteria. ORR was proportion of participants with best overall response [complete response (CR) or partial response (PR)]. |
| Time Frame | Efficacy measures from screening through end of treatment and follow-up (every 9 weeks), up to approximately 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The efficacy evaluable population included all participants enrolled in the study who received at least 1 dose of study drug. |
| Arm/Group Title | Part1/Treatment Group A : 8mg QD INCB057643 | Part1/Treatment Group A : 12mg QD INCB057643 | Part1/Treatment Group A : 16mg QD INCB057643 | Part1/Treatment Group B : 8mg QD INCB057643 | Part1/Treatment Group B : 12mg QD INCB057643 | Part1/Treatment Group C : 8mg QD INCB057643 | Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort | Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort | Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg | Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg | Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg | Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni | Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg | Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma | Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group B (TGB), based on protocol-specific criteria. Treatment Group B included any acute leukemia, HRMDS, MDS/MPN, or MF | Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group B (TGB), based on protocol-specific criteria. Treatment Group B included any acute leukemia, HRMDS, MDS/MPN, or MF. | Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group C (TGC), based on protocol-specific criteria. Treatment Group C includes subjects with MM | Initial cohort dose of INCB054763 monotherapy at the specified RP2D dose selected in Part 1 cohort escalation treatment group A (TGA), based on protocol-specific criteria. Part 2 Treatment Group A expansion included pancreatic adenocarcinoma, castration-resistant prostrate cancer, breast cancer, high grade serious ovarian cancer, glioblastoma multiform, non-hodgkin's lymphoma, ewing's sarcoma, and solid tumor or lymphoma. | Initial cohort dose of INCB057463 monotherapy at the specified RP2D dose selected in Part 1 cohort escalation treatment group B (TGB), based on protocol-specific criteria. Part 2 Treatment Group B expansion included pancreatic adenocarcinoma, castration-resistant prostrate cancer, breast cancer, high grade serious ovarian cancer, glioblastoma multiform, non-hodgkin's lymphoma, ewing's sarcoma, and solid tumor or lymphoma. | Initial cohort dose of INCB057643 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Gemcitabine) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies where Gemcitabine is relevant | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Paclitaxel) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies. | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Rucaparib) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies. | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Abiraterone + Prednisone) in Castration Resistant Prostrate Cancer | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Ruxolitinib) in Myelofibrosis. | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Azacitidine) in Acute Myeloid Leukemia and Myelodysplastic Syndrome |
| Measure Participants | 4 | 5 | 8 | 7 | 5 | 1 | 86 | 5 | 1 | 2 | 4 | 3 | 1 | 2 |
| Solid Tumors |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
100%
|
0
0%
|
0
0%
|
||||||
| Lymphoma |
1
25%
|
0
0%
|
1
12.5%
|
2
28.6%
|
||||||||||
| AML |
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
||||||||||
| Glioblastoma |
0
0%
|
|||||||||||||
| Myelodysplastic Syndrome |
0
0%
|
0
0%
|
0
0%
|
|||||||||||
| Myelofibrosis |
0
0%
|
0
0%
|
0
0%
|
|||||||||||
| Multiple Myeloma |
0
0%
|
| Title | Cmax: Maximum Observed Plasma Concentration of INCB057643. |
|---|---|
| Description | Maximum Observed Plasma Concentration INCB057643 administered as monotherapy in fasted state. |
| Time Frame | Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1 and C1D8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population includes all subjects who received at least 1 dose of study drug and had at least 1 PK sample collected and analyzed |
| Arm/Group Title | 8mg QD INCB057643 | 12mg QD INCB057643 | 16mg QD INCB057643 |
|---|---|---|---|
| Arm/Group Description | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the Part 1 TGA,TGB,TGC, and Part 2 TGA | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the Part 1 TGA,TGB, and Part 2 TGA,TGB. | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the Part 1 TGA |
| Measure Participants | 12 | 99 | 7 |
| C1D1 |
201
(83.6)
|
266
(94.7)
|
343
(93.2)
|
| C1D8 |
210
(93.2)
|
293
(113)
|
340
(165)
|
| Title | Tmax: Time to Maximum Plasma Concentration of INCB057643 |
|---|---|
| Description | Time to maximum plasma concentration of INCB057643 administered as monotherapy in fasted state |
| Time Frame | Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1 and C1D8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population includes all subjects who received at least 1 dose of study drug and had at least 1 PK sample collected and analyzed |
| Arm/Group Title | 8mg QD INCB057643 | 12mg QD INCB057643 | 16mg QD INCB057643 |
|---|---|---|---|
| Arm/Group Description | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the Part 1 TGA,TGB,TGC, and Part 2 TGA | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the Part 1 TGA,TGB, and Part 2 TGA | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the Part 1 TGA |
| Measure Participants | 12 | 99 | 7 |
| C1D1 |
2.00
|
2
|
2.00
|
| C1D8 |
1.00
|
2
|
2.00
|
| Title | AUC0-t: Area Under the Single-dose Plasma Concentration-time Curve of INCB057643 |
|---|---|
| Description | Area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration of INCB057643 administered as monotherapy in fasted state |
| Time Frame | Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population includes all subjects who received at least 1 dose of study drug and had at least 1 PK sample collected and analyzed |
| Arm/Group Title | 8mg QD INCB057643 | 12mg QD INCB057643 | 16mg QD INCB057643 |
|---|---|---|---|
| Arm/Group Description | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the Part 1 TGA,TGB,TGC, and Part 2 TGA | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the Part 1 TGA,TGB, and Part 2 TGA | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the Part 1 TGA |
| Measure Participants | 12 | 99 | 7 |
| Mean (Standard Deviation) [h*nM] |
2090
(50.1)
|
2550
(39.5)
|
3210
(34.3)
|
| Title | AUC0-24: Area Under the Steady-state Plasma Concentration-time Curve of INCB057643 Administered as Monotherapy |
|---|---|
| Description | Area under the steady-state plasma concentration-time curve over 1 dosing interval from Hour 0 to 24 for QD administration of INCB057643 administered as monotherapy in fasted state |
| Time Frame | Predose, 0.5, 1, 2, 4, 6, 8 hours on C1D8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population includes all subjects who received at least 1 dose of study drug and had at least 1 PK sample collected and analyzed |
| Arm/Group Title | 8mg QD INCB057643 | 12mg QD INCB057643 | 16mg QD INCB057643 |
|---|---|---|---|
| Arm/Group Description | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the Part 1 TGA,TGB,TGC, and Part 2 TGA | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the Part 1 TGA,TGB, and Part 2 TGA | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the Part 1 TGA |
| Measure Participants | 10 | 89 | 7 |
| Mean (Standard Deviation) [h*nM] |
1940
(45.1)
|
2740
(43.2)
|
3610
(71.9)
|
| Title | Part 2 - Cmax: Maximum Observed Plasma Concentration of INCB057643. |
|---|---|
| Description | Maximum Observed Plasma Concentration INCB057643 administered as monotherapy in fed state. |
| Time Frame | C2D1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population includes all subjects who received at least 1 dose of study drug and had at least 1 PK sample collected and analyzed |
| Arm/Group Title | 12mg QD INCB057643 |
|---|---|
| Arm/Group Description | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in Part 2 TGA and TGB |
| Measure Participants | 11 |
| Mean (Standard Deviation) [nM] |
220
(32.0)
|
| Title | Part 2-Tmax: Time to Maximum Plasma Concentration of INCB057643 |
|---|---|
| Description | Time to maximum plasma concentration of INCB057643 administered as monotherapy in fed state |
| Time Frame | C2D1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population includes all subjects who received at least 1 dose of study drug and had at least 1 PK sample collected and analyzed |
| Arm/Group Title | 12mg QD INCB057643 |
|---|---|
| Arm/Group Description | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in Part 2 TGA and TGB |
| Measure Participants | 11 |
| Median (Full Range) [hours] |
6.00
|
| Title | AUC0-24: Area Under the Steady-state Plasma Concentration-time Curve of INCB057643 Administered as Monotherapy |
|---|---|
| Description | Area under the steady-state plasma concentration-time curve over 1 dosing interval from Hour 0 to 24 for QD administration of INCB057643 administered as monotherapy in fed state. |
| Time Frame | C2D1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK evaluable population includes all subjects who received at least 1 dose of study drug and had at least 1 PK sample collected and analyzed |
| Arm/Group Title | 12mg QD INCB057643 |
|---|---|
| Arm/Group Description | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in Part 2 TGA and TGB |
| Measure Participants | 11 |
| Mean (Standard Deviation) [h*nM] |
2980
(31.5)
|
Adverse Events
| Time Frame | From screening through at least 30 days after end of treatment, up to approximately 24 months | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||||||||||||||
| Arm/Group Title | Part1/Treatment Group A : 8mg QD INCB057643 | Part1/Treatment Group A : 12mg QD INCB057643 | Part1/Treatment Group A : 16mg QD INCB057643 | Part1/Treatment Group B : 8mg QD INCB057643 | Part1/Treatment Group B : 12mg QD INCB057643 | Part1/Treatment Group C : 8mg QD INCB057643 | Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort | Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort | Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg | Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg | Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg | Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni | Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg | Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg | ||||||||||||||
| Arm/Group Description | Part1/Treatment Group A : 8mg QD INCB057643 Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma | Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA. Treatment Group A included solid tumors and lymphoma | Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group B (TGB), based on protocol-specific criteria. Treatment Group B included any acute leukemia, HRMDS, MDS/MPN, or MF. | Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group B (TGB), based on protocol-specific criteria. Treatment Group B included any acute leukemia, HRMDS, MDS/MPN, or MF. | Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group C (TGC), based on protocol-specific criteria. Treatment Group C includes subjects with MM | Initial cohort dose of INCB054763 monotherapy at the specified RP2D dose selected in Part 1 cohort escalation treatment group A (TGA), based on protocol-specific criteria. Part 2 Treatment Group A expansion included pancreatic adenocarcinoma, castration-resistant prostrate cancer, breast cancer, high grade serious ovarian cancer, glioblastoma multiform, non-hodgkin's lymphoma, ewing's sarcoma, and solid tumor or lymphoma. | Initial cohort dose of INCB057463 monotherapy at the specified RP2D dose selected in Part 1 cohort escalation treatment group B (TGB), based on protocol-specific criteria. Part 2 Treatment Group B expansion included pancreatic adenocarcinoma, castration-resistant prostrate cancer, breast cancer, high grade serious ovarian cancer, glioblastoma multiform, non-hodgkin's lymphoma, ewing's sarcoma, and solid tumor or lymphoma. | Initial cohort dose of INCB057643 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Gemcitabine) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies where Gemcitabine is relevant | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Paclitaxel) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies. | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Rucaparib) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies. | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Abiraterone + Prednisone) in Castration Resistant Prostrate Cancer | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Ruxolitinib) in Myelofibrosis. | Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Azacitidine) in Acute Myeloid Leukemia and Myelodysplastic Syndrome | ||||||||||||||
All Cause Mortality |
||||||||||||||||||||||||||||
| Part1/Treatment Group A : 8mg QD INCB057643 | Part1/Treatment Group A : 12mg QD INCB057643 | Part1/Treatment Group A : 16mg QD INCB057643 | Part1/Treatment Group B : 8mg QD INCB057643 | Part1/Treatment Group B : 12mg QD INCB057643 | Part1/Treatment Group C : 8mg QD INCB057643 | Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort | Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort | Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg | Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg | Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg | Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni | Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg | Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg | |||||||||||||||
| 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 | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/4 (50%) | 4/5 (80%) | 5/8 (62.5%) | 6/7 (85.7%) | 4/5 (80%) | 1/1 (100%) | 68/86 (79.1%) | 3/5 (60%) | 0/1 (0%) | 1/2 (50%) | 1/4 (25%) | 1/3 (33.3%) | 0/1 (0%) | 0/2 (0%) | ||||||||||||||
Serious Adverse Events |
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| Part1/Treatment Group A : 8mg QD INCB057643 | Part1/Treatment Group A : 12mg QD INCB057643 | Part1/Treatment Group A : 16mg QD INCB057643 | Part1/Treatment Group B : 8mg QD INCB057643 | Part1/Treatment Group B : 12mg QD INCB057643 | Part1/Treatment Group C : 8mg QD INCB057643 | Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort | Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort | Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg | Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg | Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg | Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni | Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg | Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg | |||||||||||||||
| 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 | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/4 (50%) | 1/5 (20%) | 4/8 (50%) | 5/7 (71.4%) | 4/5 (80%) | 1/1 (100%) | 32/86 (37.2%) | 4/5 (80%) | 0/1 (0%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 1/1 (100%) | 0/2 (0%) | ||||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||||||
| Anaemia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Febrile neutropenia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 2/5 (40%) | 2 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 2/5 (40%) | 4 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Thrombocytopenia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||||||||||||||
| Acute myocardial infarction | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Atrial fibrillation | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Cardiac arrest | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Cardiac failure congestive | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Cardio-respiratory arrest | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Tachycardia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||||||||||||
| Abdominal pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 3/86 (3.5%) | 3 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Abdominal pain upper | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Constipation | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Diarrhoea | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Gastrointestinal haemorrhage | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Intestinal obstruction | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Intestinal perforation | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Large intestinal obstruction | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Pancreatitis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Periodontal disease | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Small intestinal obstruction | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Upper gastrointestinal haemorrhage | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| General disorders | ||||||||||||||||||||||||||||
| Asthenia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Disease progression | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Performance status decreased | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||||||||||||||||||
| Bile duct obstruction | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Hepatic failure | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Infections and infestations | ||||||||||||||||||||||||||||
| Appendicitis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Cytomegalovirus oesophagitis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Herpes zoster | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/2 (0%) | 0 |
| Lung infection | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Pneumonia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 2/7 (28.6%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Pneumonia bacterial | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Pneumonia klebsiella | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Pneumonia respiratory syncytial viral | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Pneumonia streptococcal | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Sepsis | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 4/86 (4.7%) | 4 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Septic shock | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 1/1 (100%) | 1 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Staphylococcal infection | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Urinary tract infection | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Urosepsis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||
| Spinal compression fracture | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Investigations | ||||||||||||||||||||||||||||
| International normalised ratio increased | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||||||||||||||
| Decreased appetite | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Dehydration | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Failure to thrive | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Hyperglycaemia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Hyperkalaemia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||
| Back pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Muscular weakness | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Musculoskeletal pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Neck pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||||||
| Tumour pain | 1/4 (25%) | 2 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||||||||||||||
| Balance disorder | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Headache | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Ischaemic stroke | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Presyncope | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Seizure | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Spinal cord infarction | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Syncope | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||||||||||||||
| Confusional state | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Delirium | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||||||||||||||
| Acute kidney injury | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 2/7 (28.6%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| End stage renal disease | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Nephrolithiasis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Urinary retention | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||
| Acute respiratory distress syndrome | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Acute respiratory failure | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Dyspnoea | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Haemoptysis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Hypoxia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Lung infiltration | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Pleural effusion | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Pneumothorax spontaneous | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Pulmonary embolism | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Pulmonary oedema | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Respiratory failure | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 4/86 (4.7%) | 4 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Vascular disorders | ||||||||||||||||||||||||||||
| Deep vein thrombosis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Hypotension | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||||||
| Part1/Treatment Group A : 8mg QD INCB057643 | Part1/Treatment Group A : 12mg QD INCB057643 | Part1/Treatment Group A : 16mg QD INCB057643 | Part1/Treatment Group B : 8mg QD INCB057643 | Part1/Treatment Group B : 12mg QD INCB057643 | Part1/Treatment Group C : 8mg QD INCB057643 | Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort | Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort | Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg | Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg | Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg | Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni | Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg | Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg | |||||||||||||||
| 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 | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | 5/5 (100%) | 7/8 (87.5%) | 7/7 (100%) | 5/5 (100%) | 0/1 (0%) | 82/86 (95.3%) | 5/5 (100%) | 1/1 (100%) | 2/2 (100%) | 4/4 (100%) | 3/3 (100%) | 1/1 (100%) | 2/2 (100%) | ||||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||||||
| Anaemia | 0/4 (0%) | 0 | 1/5 (20%) | 2 | 3/8 (37.5%) | 3 | 4/7 (57.1%) | 4 | 3/5 (60%) | 9 | 0/1 (0%) | 0 | 15/86 (17.4%) | 17 | 4/5 (80%) | 11 | 0/1 (0%) | 0 | 1/2 (50%) | 3 | 2/4 (50%) | 2 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/2 (0%) | 0 |
| Febrile neutropenia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Increased tendency to bruise | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Iron deficiency anaemia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Leukocytosis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Leukopenia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/2 (50%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/2 (50%) | 1 |
| Lymph node pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Lymphopenia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/2 (50%) | 1 |
| Neutropenia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/2 (50%) | 2 |
| Splenic infarction | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Splenomegaly | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Thrombocytopenia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 3/8 (37.5%) | 6 | 5/7 (71.4%) | 6 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 19/86 (22.1%) | 26 | 3/5 (60%) | 3 | 0/1 (0%) | 0 | 1/2 (50%) | 1 | 2/4 (50%) | 5 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||||||||||||||
| Atrial fibrillation | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Atrioventricular block second degree | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Sinus bradycardia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Sinus tachycardia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 2/5 (40%) | 2 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Tachycardia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 4/86 (4.7%) | 4 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Ventricular arrhythmia | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||||||||||||||||||||
| Vertigo | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Eye disorders | ||||||||||||||||||||||||||||
| Cataract | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Eye pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Eyelid oedema | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Retinal haemorrhage | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Vitreous floaters | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||||||||||||
| Abdominal distension | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Abdominal pain | 0/4 (0%) | 0 | 2/5 (40%) | 2 | 2/8 (25%) | 2 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 3/86 (3.5%) | 3 | 1/5 (20%) | 2 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Abdominal pain upper | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Anal fissure | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 2 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Constipation | 0/4 (0%) | 0 | 2/5 (40%) | 2 | 1/8 (12.5%) | 1 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 19/86 (22.1%) | 19 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/2 (50%) | 1 |
| Diarrhoea | 1/4 (25%) | 1 | 2/5 (40%) | 2 | 3/8 (37.5%) | 3 | 4/7 (57.1%) | 5 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 21/86 (24.4%) | 25 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 2/4 (50%) | 3 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 1/2 (50%) | 2 |
| Dry mouth | 1/4 (25%) | 1 | 1/5 (20%) | 1 | 1/8 (12.5%) | 1 | 2/7 (28.6%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 8/86 (9.3%) | 8 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Dyspepsia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 3/86 (3.5%) | 4 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Flatulence | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Gastrooesophageal reflux disease | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Haemorrhoids | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Lip haemorrhage | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Nausea | 3/4 (75%) | 5 | 4/5 (80%) | 4 | 4/8 (50%) | 6 | 3/7 (42.9%) | 3 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 43/86 (50%) | 47 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 1/2 (50%) | 2 | 3/4 (75%) | 3 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/2 (50%) | 1 |
| Oesophageal haemorrhage | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Oral pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 3/7 (42.9%) | 3 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Stomatitis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 2/7 (28.6%) | 2 | 1/5 (20%) | 3 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 1/5 (20%) | 2 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Vomiting | 2/4 (50%) | 2 | 2/5 (40%) | 2 | 0/8 (0%) | 0 | 3/7 (42.9%) | 5 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 26/86 (30.2%) | 35 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 3/4 (75%) | 5 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| General disorders | ||||||||||||||||||||||||||||
| Asthenia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 3/86 (3.5%) | 4 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Catheter site erythema | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Catheter site haemorrhage | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Catheter site pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Chills | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Drug withdrawal syndrome | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Fatigue | 2/4 (50%) | 2 | 4/5 (80%) | 4 | 4/8 (50%) | 4 | 3/7 (42.9%) | 3 | 2/5 (40%) | 2 | 0/1 (0%) | 0 | 36/86 (41.9%) | 41 | 3/5 (60%) | 3 | 0/1 (0%) | 0 | 1/2 (50%) | 1 | 3/4 (75%) | 5 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/2 (50%) | 1 |
| Influenza like illness | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Localised oedema | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Mucosal dryness | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Mucosal haemorrhage | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Non-cardiac chest pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 2 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Oedema peripheral | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 2 | 1/1 (100%) | 1 | 0/2 (0%) | 0 |
| Performance status decreased | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Pyrexia | 1/4 (25%) | 2 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 2/7 (28.6%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 10/86 (11.6%) | 11 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/2 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||||||||||||||||||
| Hyperbilirubinaemia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/2 (50%) | 1 |
| Infections and infestations | ||||||||||||||||||||||||||||
| Acute sinusitis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Bronchitis | 1/4 (25%) | 2 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Chancroid | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Conjunctivitis | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Fungal infection | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Gingivitis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Groin infection | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Herpes simplex | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/2 (50%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Herpes zoster | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 5/86 (5.8%) | 6 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/2 (0%) | 0 |
| Lower respiratory tract infection bacterial | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 2 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Lung infection | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 2/7 (28.6%) | 2 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Lymph gland infection | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Oral candidiasis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Pneumonia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 3/86 (3.5%) | 3 | 2/5 (40%) | 2 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Sinusitis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Skin infection | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 1/1 (100%) | 1 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Staphylococcal infection | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Systemic candida | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Tooth infection | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Upper respiratory tract infection | 1/4 (25%) | 2 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Urinary tract infection | 3/4 (75%) | 3 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 5/86 (5.8%) | 5 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Viral infection | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||
| Arthropod bite | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Contusion | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 6/86 (7%) | 6 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Eye contusion | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Fall | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 2/7 (28.6%) | 2 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 4/86 (4.7%) | 5 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/2 (0%) | 0 |
| Fractured sacrum | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Infusion related reaction | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Laceration | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Transfusion reaction | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Investigations | ||||||||||||||||||||||||||||
| Activated partial thromboplastin time prolonged | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 4/86 (4.7%) | 5 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Alanine aminotransferase increased | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 7/86 (8.1%) | 7 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/2 (50%) | 1 |
| Aspartate aminotransferase increased | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 7/86 (8.1%) | 7 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Bilirubin conjugated increased | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Blood alkaline phosphatase increased | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 5/86 (5.8%) | 5 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Blood bilirubin increased | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 3 | 0/7 (0%) | 0 | 1/5 (20%) | 2 | 0/1 (0%) | 0 | 10/86 (11.6%) | 10 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Blood creatinine increased | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 5/86 (5.8%) | 8 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Blood pressure increased | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| International normalised ratio increased | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 1/7 (14.3%) | 1 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 6/86 (7%) | 8 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Neutrophil count decreased | 0/4 (0%) | 0 | 1/5 (20%) | 2 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 2 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/2 (50%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Platelet count decreased | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 2/5 (40%) | 2 | 0/1 (0%) | 0 | 8/86 (9.3%) | 8 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/2 (0%) | 0 |
| Prothrombin time prolonged | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 6/86 (7%) | 7 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/2 (50%) | 1 |
| Troponin I increased | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Troponin increased | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Weight decreased | 2/4 (50%) | 2 | 1/5 (20%) | 1 | 1/8 (12.5%) | 3 | 1/7 (14.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 6/86 (7%) | 6 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Weight increased | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| White blood cell count decreased | 0/4 (0%) | 0 | 1/5 (20%) | 3 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 2/5 (40%) | 2 | 0/1 (0%) | 0 | 5/86 (5.8%) | 6 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/2 (50%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||||||||||||||
| Decreased appetite | 2/4 (50%) | 2 | 2/5 (40%) | 2 | 3/8 (37.5%) | 3 | 3/7 (42.9%) | 3 | 2/5 (40%) | 2 | 0/1 (0%) | 0 | 27/86 (31.4%) | 28 | 3/5 (60%) | 3 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 3/4 (75%) | 3 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Dehydration | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 2 | 2/5 (40%) | 2 | 0/1 (0%) | 0 | 11/86 (12.8%) | 15 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 2/4 (50%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Hyperglycaemia | 2/4 (50%) | 2 | 0/5 (0%) | 0 | 3/8 (37.5%) | 6 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 13/86 (15.1%) | 15 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 1/1 (100%) | 1 | 0/2 (0%) | 0 |
| Hypertriglyceridaemia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/2 (0%) | 0 |
| Hypoalbuminaemia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 3/86 (3.5%) | 3 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Hypocalcaemia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 4/86 (4.7%) | 4 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/2 (50%) | 1 |
| Hypokalaemia | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 5/86 (5.8%) | 6 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Hypomagnesaemia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 4/86 (4.7%) | 6 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Hyponatraemia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 1/7 (14.3%) | 1 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 6/86 (7%) | 8 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Hypophosphataemia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 9/86 (10.5%) | 9 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Metabolic acidosis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Vitamin B12 deficiency | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||
| Arthralgia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 2/7 (28.6%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 4/86 (4.7%) | 4 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Back pain | 1/4 (25%) | 1 | 1/5 (20%) | 1 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 6/86 (7%) | 6 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Flank pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Muscle spasms | 1/4 (25%) | 2 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 4/86 (4.7%) | 4 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/2 (50%) | 1 |
| Muscular weakness | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 4/86 (4.7%) | 4 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Musculoskeletal pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 3/86 (3.5%) | 3 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Neck pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Pain in jaw | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Rotator cuff syndrome | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/2 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||||||
| Basal cell carcinoma | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Benign neoplasm | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Squamous cell carcinoma of skin | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||||||||||||||
| Brain oedema | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/2 (50%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Dizziness | 1/4 (25%) | 1 | 1/5 (20%) | 1 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 10/86 (11.6%) | 12 | 1/5 (20%) | 2 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/2 (0%) | 0 |
| Dysgeusia | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 2/8 (25%) | 2 | 3/7 (42.9%) | 3 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 16/86 (18.6%) | 16 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 1/2 (50%) | 1 | 2/4 (50%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Headache | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 3 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 5/86 (5.8%) | 5 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Neuropathy peripheral | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/2 (50%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Post herpetic neuralgia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/2 (0%) | 0 |
| Syncope | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||||||||||||||
| Agitation | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Anxiety | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 3/86 (3.5%) | 3 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Depression | 2/4 (50%) | 2 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Insomnia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||||||||||||||
| Acute kidney injury | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 1/7 (14.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 7/86 (8.1%) | 8 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Dysuria | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Haematuria | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Urinary retention | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||||||||||||||
| Penile oedema | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Vulvovaginal erythema | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||
| Chronic obstructive pulmonary disease | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Cough | 1/4 (25%) | 1 | 1/5 (20%) | 1 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 2/5 (40%) | 2 | 0/1 (0%) | 0 | 10/86 (11.6%) | 12 | 2/5 (40%) | 2 | 0/1 (0%) | 0 | 1/2 (50%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Dyspnoea | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/8 (0%) | 0 | 2/7 (28.6%) | 2 | 2/5 (40%) | 2 | 0/1 (0%) | 0 | 9/86 (10.5%) | 9 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Dyspnoea exertional | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Epistaxis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 2/7 (28.6%) | 2 | 4/5 (80%) | 9 | 0/1 (0%) | 0 | 5/86 (5.8%) | 5 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Haemoptysis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 3/86 (3.5%) | 3 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Hypoxia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 2/7 (28.6%) | 2 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 3/5 (60%) | 3 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Nasal congestion | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 3/86 (3.5%) | 3 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Oropharyngeal pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 2/7 (28.6%) | 2 | 1/5 (20%) | 2 | 0/1 (0%) | 0 | 4/86 (4.7%) | 4 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/2 (50%) | 1 |
| Pleural effusion | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 6/86 (7%) | 6 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Pneumonitis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Productive cough | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 2/4 (50%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Pulmonary oedema | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Respiratory failure | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Sneezing | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Upper-airway cough syndrome | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Wheezing | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||||
| Acne | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Alopecia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/2 (50%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Angioedema | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Dry skin | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 2/7 (28.6%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Erythema | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Pain of skin | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Petechiae | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 2 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Pruritus | 1/4 (25%) | 1 | 1/5 (20%) | 1 | 1/8 (12.5%) | 1 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 4/86 (4.7%) | 4 | 2/5 (40%) | 2 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Purpura | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 3 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Rash | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Scab | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Skin ulcer | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/86 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Vascular disorders | ||||||||||||||||||||||||||||
| Haematoma | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 1/7 (14.3%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/86 (1.2%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Hot flush | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 2/86 (2.3%) | 2 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Hypertension | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 2/8 (25%) | 2 | 0/7 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 3/86 (3.5%) | 3 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
| Hypotension | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 1/5 (20%) | 2 | 0/1 (0%) | 0 | 3/86 (3.5%) | 3 | 1/5 (20%) | 2 | 0/1 (0%) | 0 | 0/2 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
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 | 1-855-463-3463 |
| medinfo@incyte.com |
Responsible Party:
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT02711137
Other Study ID Numbers:
- INCB 57643-101
First Posted:
Mar 17, 2016
Last Update Posted:
Apr 28, 2022
Last Verified:
Apr 1, 2022