BI836826 Dose Escalation in Relapsed Chronic Lymphocytic Leukaemia (CLL)

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01296932
• Collaborator: (none)
• Enrollment: 37
• Locations: 10
• Arm: 1
• Actual Duration (Months): 76.9
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Adult patients with chronic lymphocytic leukaemia who experience a relapse after at least two prior treatment regimens may be enrolled in this trial. The trial will examine whether monotherapy with BI 836826 is safe and tolerable at escalating dose levels.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Lymphocytic, Chronic, B-Cell	Drug: BI 836826	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I, Open, Dose Escalation Trial With BI 836826 in Patients With Advanced Chronic Lymphocytic Leukaemia
• Actual Study Start Date: Feb 11, 2011
• Actual Primary Completion Date: May 30, 2017
• Actual Study Completion Date: Jul 10, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Patients with relapsed CLL Patients with relapsed CLL after at least two prior treatment regimens will receive BI 836826.	Drug: BI 836826; Monotherapy with BI 836826 at escalating dose levels administered as an intravenous infusion.

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Dose-Limiting Toxicities Adverse Events (DLTs) [14 days after first administration of BI836826 (MTD evaluation period)]

   Dose-Limiting Toxicities (DLTs) were defined as any drug-related non-haematologic adverse event of Common Terminology Criteria for AE (CTCAE) Grade 3 or higher, except infusion related reactions associated with the administration of BI 836826. In addition complications due to haematologic AEs were considered as DLTs and were added in more detail in an amendment later on.

2. Maximum Tolerated Dose (MTD) [14 days after first administration of BI836826 (MTD evaluation period)]

   The maximum tolerated dose (MTD) was defined as the highest dose of BI 836826 studied for which the incidence of DLT was no more than 17% (i.e. 1 out of 6 patients) during the first treatment cycle. For those patients who received more than 1 cycle of BI 836826, all AEs corresponding to the DLT were considered for the purpose of confirming the MTD and for the selection of the recommended dose for treatment of the expansion cohort and for further development. All DLTs, occurring during the first or repeated treatment cycle were reported as significant AEs. As it was not possible to recruit a sufficient number of patients whilst the first part of the trial was still in progress, the recruitment was ended by the sponsor before the MTD or optimal biological dose (OBD) was reached.

Secondary Outcome Measures

1. Best Percentage Change From Baseline in Number of Lymphocytes in the Peripheral Blood [baseline and ≥8 day after a completed infusion of a cycle and before Chronic Lymphocytic Leukemia (CLL) therapy; data collected up to cut-off date 26Oct2016, Up to 1809 days]

   In most patients with relapsed or refractory chronic lymphocytic leukaemia (CLL), malignant B-cells represent the majority of lymphocytes in the peripheral blood. Reduction of CLL-cells was assessed in the peripheral blood by absolute lymphocyte count, and flow cytometry. The number of lymphocytes in the peripheral blood was analysed in terms of the best percentage change from baseline until start of subsequent CLL therapy or progressive disease (PD).

2. Number of Patients With Improved Haemoglobin Count for at Least Two Subsequent Response Assessments [≥8 day after a completed infusion of a cycle and before Chronic Lymphocytic Leukemia (CLL) therapy; data collected up to cut-off date 26Oct2016, Up to 1809 days]

   In patients with haemoglobin counts below the limits of normal at baseline, improvement in this count during therapy potentially indicated a benefit for the patient. Number of patients with improved haemoglobin count for at least two subsequent response assessments which fulfil International Workshop on Chronic Lymphocytic Leukemia (IWCLL) response criteria for Complete Remission (CR) or Partial Remission (PR). The response was assessed before Progressive Disease (PD) or start of new Chronic Lymphocytic Leukaemia (CLL) therapy.

3. Number of Patients With Improved Platelet Count for at Least Two Subsequent Response Assessments [≥8 day after a completed infusion of a cycle and before Chronic Lymphocytic Leukemia (CLL) therapy; data collected up to cut-off date 26Oct2016, Up to 1809 days]

   In patients with platelet counts below the limits of normal at baseline, improvement in this count during therapy potentially indicated a benefit for the patient. Number of patients with improved platelet count for at least two subsequent response assessments which fulfil International Workshop on Chronic Lymphocytic Leukemia (IWCLL) response criteria for Complete Remission (CR) or Partial Remission (PR). The response was assessed before Progressive Disease (PD) or start of new Chronic Lymphocytic Leukaemia (CLL) therapy.

4. Number of Patients With Improved Neutrophil Count for at Least Two Subsequent Response Assessments [≥8 day after a completed infusion of a cycle and before Chronic Lymphocytic Leukemia (CLL) therapy; data collected up to cut-off date 26Oct2016, Up to 1809 days]

   In patients with neutrophil count below the limits of normal at baseline, improvement in this count during therapy potentially indicated a benefit for the patient. Number of patients with improved neutrophil count for at least two subsequent response assessments which fulfil International Workshop on Chronic Lymphocytic Leukemia (IWCLL) response criteria for Complete Remission (CR) or Partial Remission (PR). The response was assessed before Progressive Disease (PD) or start of new Chronic Lymphocytic Leukaemia (CLL) therapy.

5. Best Overall Response According to 'International Workshop on Chronic Lymphocytic Leukemia' (IWCLL) Criteria [Data collected up to cut-off date 26Oct2016 until Progressive disease (PD) to start of next Chronic Lymphocytic Leukaemia (CLL) therapy, Up to 1809 days.]

   Response was assessed according to the IWCLL (International Workshop on Chronic Lymphocytic Leukemia) guidelines based on laboratory data from the peripheral blood and clinical examination by the investigator after each cycle prior to administration of the next dose of BI 836826, at the end of the treatment (EOT) visit, and at all Follow-up Visits. Best overall response will be analysed descriptively. Frequency distributions will be used to examine this endpoint.

6. Progression-free Survival [Data collected up to cut-off date 26Oct2016, Up to 1809 days.]

   Progression-free survival (PFS) was defined as the time from the first administration of BI 836826 until disease progression or death, whichever occurred first. Disease progression= At least one of the following: 50+% increase in blood lymphocytes over baseline with an absolute number of B-lymphocytes of at least 5x109/L Progression of lymphadenopathy 50+% increase in the previously noted enlargement of the liver or new appearance of hepatomegaly 50+% increase in the previously noted enlargement of the spleen or new appearance of splenomegaly 50+% Decrease of platelet counts or to less than 100x109/L secondary to CLL and unrelated to autoimmune cytopenia Decrease of haemoglobin levels by more than 20 g/L, or to less than 100 g/L secondary to CLL and unrelated to autoimmune cytopenia T Transformation to a more aggressive histology, e.g. Richter syndrome.

7. Failure-free Survival [Data collected up to cut-off date 26Oct2016, Up to 1809 days.]

   Failure-free survival (FFS) was defined as the time from the first administration of BI 836826 until disease progression or death, or start of next Chronic Lymphocytic Leukemia (CLL) therapy, whichever occurred first. Disease progression= At least one of the following: 50+% increase in blood lymphocytes over baseline with an absolute number of B-lymphocytes of at least 5x109/L Progression of lymphadenopathy 50+% increase in the previously noted enlargement of the liver or new appearance of hepatomegaly 50+% increase in the previously noted enlargement of the spleen or new appearance of splenomegaly 50+% Decrease of platelet counts or to less than 100x109/L secondary to CLL and unrelated to autoimmune cytopenia Decrease of haemoglobin levels by more than 20 g/L, or to less than 100 g/L secondary to CLL and unrelated to autoimmune cytopenia T Transformation to a more aggressive histology, e.g. Richter syndrome.

Eligibility Criteria

Criteria

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

Inclusion criteria:

1. Diagnosis of relapsed or refractory chronic lymphocytic leukaemia.

2. At least two prior treatment regimens for chronic lymphocytic leukaemia.

3. At least one criterion for active disease as defined by the International Workshop on CLL.

4. Absolute lymphocyte count lower than 200 x 10^9/l .

5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2.

6. Age 18 years or older.

7. Written informed consent which is consistent with International Conference on Harmonisation - Good Clinical Practice (ICH-GCP) guidelines and local legislation.

Exclusion criteria:

1. Treatment with anti Cluster of Differentiation (CD) 20 therapy within 4 weeks, or alemtuzumab within 8 weeks, or any cytotoxic antileukemia therapy within 2 weeks, Ibrutinib or Idelalisib within 1 week prior to the first administration of the trial drug.

2. Prior allogeneic stem cell transplantation.

3. Active autoimmune haemolytic anemia.

4. Active autoimmune thrombocytopenia.

5. Known transformation to an aggressive B-cell malignancy.

6. Concurrent treatment with relevant doses of systemic glucocorticosteroids.

7. Prior history of malignancy other than chronic lymphocytic leukaemia (exceptions to this rule are defined in the clinical trial protocol).

8. Aspartate aminotransferase or alanine aminotransferase > 2.5 x upper limit of normal.

9. Total bilirubin > 1.5 x upper limit of normal.

10. Absolute Neutrophil Count < 1.000/µl.

11. Platelets < 25.000/µL.

12. Estimated Glomerular Filtration Rate <45 mL/min.

13. Proteinuria Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or higher.

14. Significant concurrent disease.

15. Any infectious disease requiring treatment at the time of enrolment or within the previous 2 weeks.

16. Hepatitis B or C.

17. Human Immunodeficiency Virus (HIV) infection.

18. Cytomegalovirus (CMV) viremia.

19. Women of childbearing potential not using a highly effective method of birth control during the trial until one year after the last dose.

20. Pregnancy or breast feeding.

21. Known or suspected active alcohol or drug abuse.

22. Treatment with another investigational drug within the past four weeks before start of therapy or concomitantly with this trial.

23. Prior treatment with BI 836826.

24. Patients unable to comply with the protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brussels - UNIV Saint-Luc	Bruxelles		Belgium	1200
2	Edegem - UNIV UZ Antwerpen	Edegem		Belgium	2650
3	UNIV UZ Gent	Gent		Belgium	9000
4	INS Paoli-Calmettes	Marseille		France	13273
5	CTR Investigation Clinique, onco, Montpellier	Montpellier Cedex 5		France	34295
6	INS Universitaire du Cancer	Toulouse		France	31059
7	Universitätsklinikum Frankfurt	Frankfurt am Main		Germany	60590
8	Universitätsklinikum Heidelberg	Heidelberg		Germany	69120
9	Universitätsklinikum Köln (AöR)	Köln		Germany	50937
10	Universitätsklinikum Ulm	Ulm		Germany	89081

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

• Statistical Analysis Plan - Oct 13, 2016
• Study Protocol - Mar 4, 2015

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01296932
• Other Study ID Numbers: 1270.1; 2010-021488-34
• First Posted: Feb 16, 2011
• Last Update Posted: Aug 20, 2020
• Last Verified: Aug 1, 2020

• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; BI 836826

Study Results

Participant Flow

Recruitment Details	This was a Phase-1,single arm,open-label,dose escalation trial, patients with advanced chronic lymphocytic leukemia. While the first part of the trial was still in progress, recruitment was ended by the sponsor before the maximum tolerated dose(MTD) or Optimal Biological Dose(OBD) was reached.
Pre-assignment Detail	All patients were screened for eligibility to participate in the trial. Patients attended specialist sites to ensure that all patients met all inclusion/exclusion criteria. Patients were not to be entered to trial treatment if any one of the specific entry criteria were not met.

Arm/Group Title	BI 836826 1 Milligram	BI 836826 3 Milligram	BI 836826 9 Milligram	BI 836826 25 Milligram	BI 836826 50 Milligram	BI 836826 100 Milligram	BI 836826 200 Milligram	BI 836826 400 Milligram	BI 836826 800 Milligram
Arm/Group Description	Patients were administered BI 836826-1 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle	Patients were administered BI 836826-3 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle	Patients were administered BI 836826-9 milligram solution for infusion after dilution intravenously as one or two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-25 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-50 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-100 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-200 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-400 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-800 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles
Period Title: Overall Study
STARTED	3	3	6	6	3	3	6	3	4
COMPLETED	0	0	0	0	0	0	0	1	0
NOT COMPLETED	3	3	6	6	3	3	6	2	4

Baseline Characteristics

Arm/Group Title	BI 836826 1 Milligram	BI 836826 3 Milligram	BI 836826 9 Milligram	BI 836826 25 Milligram	BI 836826 50 Milligram	BI 836826 100 Milligram	BI 836826 200 Milligram	BI 836826 400 Milligram	BI 836826 800 Milligram	Total
Arm/Group Description	Patients were administered BI 836826-1 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle	Patients were administered BI 836826-3 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle	Patients were administered BI 836826-9 milligram solution for infusion after dilution intravenously as one or two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-25 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-50 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-100 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-200 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-400 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-800 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Total of all reporting groups
Overall Participants	3	3	6	6	3	3	6	3	4	37
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	67.7 (8.4)	74.3 (5.7)	63.3 (10.0)	58.7 (9.6)	63.3 (13.2)	61.0 (17.0)	73.3 (5.4)	70.7 (11.4)	69.5 (6.5)	66.5 (10.2)
Sex: Female, Male (Count of Participants)
Female	2 66.7%	1 33.3%	1 16.7%	0 0%	1 33.3%	1 33.3%	4 66.7%	0 0%	1 25%	11 29.7%
Male	1 33.3%	2 66.7%	5 83.3%	6 100%	2 66.7%	2 66.7%	2 33.3%	3 100%	3 75%	26 70.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
White	3 100%	2 66.7%	4 66.7%	2 33.3%	1 33.3%	2 66.7%	2 33.3%	3 100%	2 50%	21 56.8%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 33.3%	2 33.3%	4 66.7%	2 66.7%	1 33.3%	4 66.7%	0 0%	2 50%	16 43.2%

Outcome Measures

1. Secondary Outcome

Title	Best Percentage Change From Baseline in Number of Lymphocytes in the Peripheral Blood
Description	In most patients with relapsed or refractory chronic lymphocytic leukaemia (CLL), malignant B-cells represent the majority of lymphocytes in the peripheral blood. Reduction of CLL-cells was assessed in the peripheral blood by absolute lymphocyte count, and flow cytometry. The number of lymphocytes in the peripheral blood was analysed in terms of the best percentage change from baseline until start of subsequent CLL therapy or progressive disease (PD).
Time Frame	baseline and ≥8 day after a completed infusion of a cycle and before Chronic Lymphocytic Leukemia (CLL) therapy; data collected up to cut-off date 26Oct2016, Up to 1809 days

Outcome Measure Data

Analysis Population Description

All patients who received at least one application of the drug BI 836826, had a baseline and at least one post-baseline assessment of the number of lymphocytes in the peripheral blood.

Arm/Group Title	BI 836826 1 Milligram	BI 836826 3 Milligram	BI 836826 9 Milligram	BI 836826 25 Milligram	BI 836826 50 Milligram	BI 836826 100 Milligram	BI 836826 200 Milligram	BI 836826 400 Milligram	BI 836826 800 Milligram
Arm/Group Description	Patients were administered BI 836826-1 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle	Patients were administered BI 836826-3 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle	Patients were administered BI 836826-9 milligram solution for infusion after dilution intravenously as one or two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-25 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-50 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-100 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-200 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-400 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-800 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles
Measure Participants	3	3	6	5	3	3	6	3	4
Mean (Standard Deviation) [Percentage of change (%)]	-11.39 (31.39)	-21.20 (10.08)	-48.21 (57.39)	-48.15 (34.01)	-49.35 (31.44)	-81.81 (11.03)	-79.22 (39.94)	-93.40 (9.76)	-47.14 (103.29)

2. Secondary Outcome

Title	Number of Patients With Improved Haemoglobin Count for at Least Two Subsequent Response Assessments
Description	In patients with haemoglobin counts below the limits of normal at baseline, improvement in this count during therapy potentially indicated a benefit for the patient. Number of patients with improved haemoglobin count for at least two subsequent response assessments which fulfil International Workshop on Chronic Lymphocytic Leukemia (IWCLL) response criteria for Complete Remission (CR) or Partial Remission (PR). The response was assessed before Progressive Disease (PD) or start of new Chronic Lymphocytic Leukaemia (CLL) therapy.
Time Frame	≥8 day after a completed infusion of a cycle and before Chronic Lymphocytic Leukemia (CLL) therapy; data collected up to cut-off date 26Oct2016, Up to 1809 days

Outcome Measure Data

Analysis Population Description

Treated Set (TS): All patients who received at least one application of the drug BI 836826.

Arm/Group Title	BI 836826 1 Milligram	BI 836826 3 Milligram	BI 836826 9 Milligram	BI 836826 25 Milligram	BI 836826 50 Milligram	BI 836826 100 Milligram	BI 836826 200 Milligram	BI 836826 400 Milligram	BI 836826 800 Milligram
Arm/Group Description	Patients were administered BI 836826-1 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle	Patients were administered BI 836826-3 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle	Patients were administered BI 836826-9 milligram solution for infusion after dilution intravenously as one or two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-25 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-50 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-100 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-200 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-400 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-800 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles
Measure Participants	3	3	6	6	3	3	6	3	4
NO	3 100%	2 66.7%	3 50%	4 66.7%	2 66.7%	1 33.3%	2 33.3%	1 33.3%	4 100%
YES	0 0%	1 33.3%	3 50%	2 33.3%	1 33.3%	2 66.7%	4 66.7%	2 66.7%	0 0%

3. Secondary Outcome

Title	Number of Patients With Improved Platelet Count for at Least Two Subsequent Response Assessments
Description	In patients with platelet counts below the limits of normal at baseline, improvement in this count during therapy potentially indicated a benefit for the patient. Number of patients with improved platelet count for at least two subsequent response assessments which fulfil International Workshop on Chronic Lymphocytic Leukemia (IWCLL) response criteria for Complete Remission (CR) or Partial Remission (PR). The response was assessed before Progressive Disease (PD) or start of new Chronic Lymphocytic Leukaemia (CLL) therapy.
Time Frame	≥8 day after a completed infusion of a cycle and before Chronic Lymphocytic Leukemia (CLL) therapy; data collected up to cut-off date 26Oct2016, Up to 1809 days

Outcome Measure Data

Analysis Population Description

TS

Arm/Group Title	BI 836826 1 Milligram	BI 836826 3 Milligram	BI 836826 9 Milligram	BI 836826 25 Milligram	BI 836826 50 Milligram	BI 836826 100 Milligram	BI 836826 200 Milligram	BI 836826 400 Milligram	BI 836826 800 Milligram
Arm/Group Description	Patients were administered BI 836826-1 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle	Patients were administered BI 836826-3 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle	Patients were administered BI 836826-9 milligram solution for infusion after dilution intravenously as one or two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-25 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-50 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-100 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-200 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-400 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-800 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles
Measure Participants	3	3	6	6	3	3	6	3	4
NO	2 66.7%	2 66.7%	2 33.3%	3 50%	3 100%	1 33.3%	3 50%	0 0%	3 75%
YES	1 33.3%	1 33.3%	4 66.7%	3 50%	0 0%	2 66.7%	3 50%	3 100%	1 25%

4. Secondary Outcome

Title	Number of Patients With Improved Neutrophil Count for at Least Two Subsequent Response Assessments
Description	In patients with neutrophil count below the limits of normal at baseline, improvement in this count during therapy potentially indicated a benefit for the patient. Number of patients with improved neutrophil count for at least two subsequent response assessments which fulfil International Workshop on Chronic Lymphocytic Leukemia (IWCLL) response criteria for Complete Remission (CR) or Partial Remission (PR). The response was assessed before Progressive Disease (PD) or start of new Chronic Lymphocytic Leukaemia (CLL) therapy.
Time Frame	≥8 day after a completed infusion of a cycle and before Chronic Lymphocytic Leukemia (CLL) therapy; data collected up to cut-off date 26Oct2016, Up to 1809 days

Outcome Measure Data

Analysis Population Description

TS

Arm/Group Title	BI 836826 1 Milligram	BI 836826 3 Milligram	BI 836826 9 Milligram	BI 836826 25 Milligram	BI 836826 50 Milligram	BI 836826 100 Milligram	BI 836826 200 Milligram	BI 836826 400 Milligram	BI 836826 800 Milligram
Arm/Group Description	Patients were administered BI 836826-1 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle	Patients were administered BI 836826-3 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle	Patients were administered BI 836826-9 milligram solution for infusion after dilution intravenously as one or two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-25 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-50 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-100 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-200 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-400 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-800 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles
Measure Participants	3	3	6	6	3	3	6	3	4
YES	1 33.3%	3 100%	5 83.3%	4 66.7%	1 33.3%	2 66.7%	5 83.3%	3 100%	1 25%
NO	2 66.7%	0 0%	1 16.7%	2 33.3%	2 66.7%	1 33.3%	1 16.7%	0 0%	3 75%

5. Secondary Outcome

Title	Best Overall Response According to 'International Workshop on Chronic Lymphocytic Leukemia' (IWCLL) Criteria
Description	Response was assessed according to the IWCLL (International Workshop on Chronic Lymphocytic Leukemia) guidelines based on laboratory data from the peripheral blood and clinical examination by the investigator after each cycle prior to administration of the next dose of BI 836826, at the end of the treatment (EOT) visit, and at all Follow-up Visits. Best overall response will be analysed descriptively. Frequency distributions will be used to examine this endpoint.
Time Frame	Data collected up to cut-off date 26Oct2016 until Progressive disease (PD) to start of next Chronic Lymphocytic Leukaemia (CLL) therapy, Up to 1809 days.

Outcome Measure Data

Analysis Population Description

TS

Arm/Group Title	BI 836826 1 Milligram	BI 836826 3 Milligram	BI 836826 9 Milligram	BI 836826 25 Milligram	BI 836826 50 Milligram	BI 836826 100 Milligram	BI 836826 200 Milligram	BI 836826 400 Milligram	BI 836826 800 Milligram
Arm/Group Description	Patients were administered BI 836826-1 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle	Patients were administered BI 836826-3 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle	Patients were administered BI 836826-9 milligram solution for infusion after dilution intravenously as one or two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-25 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-50 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-100 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-200 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-400 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-800 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles
Measure Participants	3	3	6	6	3	3	6	3	4
Complete remission	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Complete remission with incomplete marrow recovery	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Partial remission	0 0%	0 0%	4 66.7%	1 16.7%	0 0%	0 0%	4 66.7%	2 66.7%	2 50%
Stable disease	3 100%	3 100%	2 33.3%	4 66.7%	3 100%	3 100%	2 33.3%	1 33.3%	2 50%
Progressive disease	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Not evaluable	0 0%	0 0%	0 0%	1 16.7%	0 0%	0 0%	0 0%	0 0%	0 0%

6. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival (PFS) was defined as the time from the first administration of BI 836826 until disease progression or death, whichever occurred first. Disease progression= At least one of the following: 50+% increase in blood lymphocytes over baseline with an absolute number of B-lymphocytes of at least 5x109/L Progression of lymphadenopathy 50+% increase in the previously noted enlargement of the liver or new appearance of hepatomegaly 50+% increase in the previously noted enlargement of the spleen or new appearance of splenomegaly 50+% Decrease of platelet counts or to less than 100x109/L secondary to CLL and unrelated to autoimmune cytopenia Decrease of haemoglobin levels by more than 20 g/L, or to less than 100 g/L secondary to CLL and unrelated to autoimmune cytopenia T Transformation to a more aggressive histology, e.g. Richter syndrome.
Time Frame	Data collected up to cut-off date 26Oct2016, Up to 1809 days.

Outcome Measure Data

Analysis Population Description

TS

Arm/Group Title	BI 836826 1 Milligram	BI 836826 3 Milligram	BI 836826 9 Milligram	BI 836826 25 Milligram	BI 836826 50 Milligram	BI 836826 100 Milligram	BI 836826 200 Milligram	BI 836826 400 Milligram	BI 836826 800 Milligram
Arm/Group Description	Patients were administered BI 836826-1 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle	Patients were administered BI 836826-3 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle	Patients were administered BI 836826-9 milligram solution for infusion after dilution intravenously as one or two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-25 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-50 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-100 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-200 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-400 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-800 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles
Measure Participants	3	3	6	6	3	3	6	3	4
Median (Inter-Quartile Range) [Days]	57.0	86.0	133.5	81.0	85.0	114.0	196.5	113.0	68.0

7. Secondary Outcome

Title	Failure-free Survival
Description	Failure-free survival (FFS) was defined as the time from the first administration of BI 836826 until disease progression or death, or start of next Chronic Lymphocytic Leukemia (CLL) therapy, whichever occurred first. Disease progression= At least one of the following: 50+% increase in blood lymphocytes over baseline with an absolute number of B-lymphocytes of at least 5x109/L Progression of lymphadenopathy 50+% increase in the previously noted enlargement of the liver or new appearance of hepatomegaly 50+% increase in the previously noted enlargement of the spleen or new appearance of splenomegaly 50+% Decrease of platelet counts or to less than 100x109/L secondary to CLL and unrelated to autoimmune cytopenia Decrease of haemoglobin levels by more than 20 g/L, or to less than 100 g/L secondary to CLL and unrelated to autoimmune cytopenia T Transformation to a more aggressive histology, e.g. Richter syndrome.
Time Frame	Data collected up to cut-off date 26Oct2016, Up to 1809 days.

Outcome Measure Data

Analysis Population Description

TS

Arm/Group Title	BI 836826 1 Milligram	BI 836826 3 Milligram	BI 836826 9 Milligram	BI 836826 25 Milligram	BI 836826 50 Milligram	BI 836826 100 Milligram	BI 836826 200 Milligram	BI 836826 400 Milligram	BI 836826 800 Milligram
Arm/Group Description	Patients were administered BI 836826-1 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle	Patients were administered BI 836826-3 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle	Patients were administered BI 836826-9 milligram solution for infusion after dilution intravenously as one or two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-25 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-50 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-100 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-200 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-400 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-800 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles
Measure Participants	3	3	6	6	3	3	6	3	4
Median (Inter-Quartile Range) [Days]	57.0	106.0	152.5	81.0	85.0	114.0	196.5	149.0	100.0

8. Primary Outcome

Title	Number of Patients With Dose-Limiting Toxicities Adverse Events (DLTs)
Description	Dose-Limiting Toxicities (DLTs) were defined as any drug-related non-haematologic adverse event of Common Terminology Criteria for AE (CTCAE) Grade 3 or higher, except infusion related reactions associated with the administration of BI 836826. In addition complications due to haematologic AEs were considered as DLTs and were added in more detail in an amendment later on.
Time Frame	14 days after first administration of BI836826 (MTD evaluation period)

Outcome Measure Data

Analysis Population Description

The maximum tolerated dose (MTD) evaluation set: This includes all patients who were documented to have received at least one dose of trial medication and were not replaced for the MTD evaluation.

Arm/Group Title	BI 836826 1 Milligram	BI 836826 3 Milligram	BI 836826 9 Milligram	BI 836826 25 Milligram	BI 836826 50 Milligram	BI 836826 100 Milligram	BI 836826 200 Milligram	BI 836826 400 Milligram	BI 836826 800 Milligram
Arm/Group Description	Patients were administered BI 836826-1 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle	Patients were administered BI 836826-3 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle	Patients were administered BI 836826-9 milligram solution for infusion after dilution intravenously as one or two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-25 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-50 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-100 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-200 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-400 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles	Patients were administered BI 836826-800 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles
Measure Participants	3	3	6	5	3	3	6	3	3
Total with dose limiting toxicities adverse events	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%	1 25%

9. Primary Outcome

Title	Maximum Tolerated Dose (MTD)
Description	The maximum tolerated dose (MTD) was defined as the highest dose of BI 836826 studied for which the incidence of DLT was no more than 17% (i.e. 1 out of 6 patients) during the first treatment cycle. For those patients who received more than 1 cycle of BI 836826, all AEs corresponding to the DLT were considered for the purpose of confirming the MTD and for the selection of the recommended dose for treatment of the expansion cohort and for further development. All DLTs, occurring during the first or repeated treatment cycle were reported as significant AEs. As it was not possible to recruit a sufficient number of patients whilst the first part of the trial was still in progress, the recruitment was ended by the sponsor before the MTD or optimal biological dose (OBD) was reached.
Time Frame	14 days after first administration of BI836826 (MTD evaluation period)

Outcome Measure Data

Analysis Population Description

The trial was discontinued prematurely due to lack of recruitment before the MTD based on the frequency of patients with DLTs in the first treatment cycle was reached.

Arm/Group Title	BI 836826
Arm/Group Description	Patients were administered BI 836826 solution for infusion after dilution intravenously as one or two doses within the first cycle followed by a single doses within all following 14-day cycles in the higher dose groups (>9 milligram BI 836826).
Measure Participants	0

Adverse Events

Time Frame	From the first dose of study medication until 6 weeks after last administration of BI 836826, up to 136 weeks
Adverse Event Reporting Description	The Treated set (TS) was used for adverse event reporting. (TS: This patient set consists of all patients who received at least one application of the BI drug BI 836826.)
Arm/Group Title	BI 836826 1 Milligram		BI 836826 3 Milligram		BI 836826 9 Milligram		BI 836826 25 Milligram		BI 836826 50 Milligram		BI 836826 100 Milligram		BI 836826 200 Milligram		BI 836826 400 Milligram		BI 836826 800 Milligram
Arm/Group Description	Patients were administered BI 836826-1 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle		Patients were administered BI 836826-3 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle		Patients were administered BI 836826-9 milligram solution for infusion after dilution intravenously as one or two doses within the first cycle followed by single doses within all following 14-day cycles		Patients were administered BI 836826-25 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles		Patients were administered BI 836826-50 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles		Patients were administered BI 836826-100 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles		Patients were administered BI 836826-200 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles		Patients were administered BI 836826-400 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles		Patients were administered BI 836826-800 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles
All Cause Mortality
	BI 836826 1 Milligram		BI 836826 3 Milligram		BI 836826 9 Milligram		BI 836826 25 Milligram		BI 836826 50 Milligram		BI 836826 100 Milligram		BI 836826 200 Milligram		BI 836826 400 Milligram		BI 836826 800 Milligram
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Serious Adverse Events
	BI 836826 1 Milligram		BI 836826 3 Milligram		BI 836826 9 Milligram		BI 836826 25 Milligram		BI 836826 50 Milligram		BI 836826 100 Milligram		BI 836826 200 Milligram		BI 836826 400 Milligram		BI 836826 800 Milligram
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		1/3 (33.3%)		4/6 (66.7%)		3/6 (50%)		1/3 (33.3%)		1/3 (33.3%)		5/6 (83.3%)		1/3 (33.3%)		2/4 (50%)
Blood and lymphatic system disorders
Febrile bone marrow aplasia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Febrile neutropenia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Haemolytic anaemia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Leukopenia	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Neutropenia	0/3 (0%)		0/3 (0%)		2/6 (33.3%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Thrombocytopenia	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Cardiac disorders
Bundle branch block right	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Cardiac failure	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Left ventricular failure	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
General disorders
Pyrexia	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		2/6 (33.3%)		0/3 (0%)		0/4 (0%)
Hepatobiliary disorders
Cholecystitis	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Infections and infestations
Bacterial sepsis	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Cryptococcosis	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Cytomegalovirus infection	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Device related infection	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Erysipelas	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Pneumonia	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Pseudomonal sepsis	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Respiratory tract infection	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Respiratory tract infection fungal	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Sepsis	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Injury, poisoning and procedural complications
Infusion related reaction	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Investigations
Alanine aminotransferase increased	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Aspartate aminotransferase increased	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Metabolism and nutrition disorders
Hypercalcaemia	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Tumour lysis syndrome	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Bone pain	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Squamous cell carcinoma of skin	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Renal and urinary disorders
Acute kidney injury	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Vascular disorders
Vena cava thrombosis	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	BI 836826 1 Milligram		BI 836826 3 Milligram		BI 836826 9 Milligram		BI 836826 25 Milligram		BI 836826 50 Milligram		BI 836826 100 Milligram		BI 836826 200 Milligram		BI 836826 400 Milligram		BI 836826 800 Milligram
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		6/6 (100%)		6/6 (100%)		3/3 (100%)		3/3 (100%)		6/6 (100%)		3/3 (100%)		4/4 (100%)
Blood and lymphatic system disorders
Anaemia	0/3 (0%)		1/3 (33.3%)		4/6 (66.7%)		3/6 (50%)		1/3 (33.3%)		3/3 (100%)		2/6 (33.3%)		1/3 (33.3%)		2/4 (50%)
Eosinophilia	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Leukocytosis	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Leukopenia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		2/6 (33.3%)		3/3 (100%)		1/4 (25%)
Lymph node pain	1/3 (33.3%)		0/3 (0%)		2/6 (33.3%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Neutropenia	0/3 (0%)		0/3 (0%)		3/6 (50%)		3/6 (50%)		1/3 (33.3%)		2/3 (66.7%)		3/6 (50%)		1/3 (33.3%)		3/4 (75%)
Thrombocytopenia	1/3 (33.3%)		1/3 (33.3%)		4/6 (66.7%)		1/6 (16.7%)		1/3 (33.3%)		1/3 (33.3%)		2/6 (33.3%)		2/3 (66.7%)		3/4 (75%)
Cardiac disorders
Aortic valve disease	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Arrhythmia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		2/6 (33.3%)		0/3 (0%)		0/4 (0%)
Atrial fibrillation	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Atrioventricular block second degree	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Bradycardia	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Diastolic dysfunction	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Hypertensive heart disease	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Mitral valve calcification	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Mitral valve incompetence	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Myocardial ischaemia	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Palpitations	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		1/3 (33.3%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Sinus bradycardia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Sinus tachycardia	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Tachycardia	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Tricuspid valve incompetence	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Ear and labyrinth disorders
Ear pain	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Middle ear effusion	1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Vertigo	0/3 (0%)		1/3 (33.3%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Eye disorders
Cataract	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Conjunctival haemorrhage	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Eye pain	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Eyelid oedema	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Keratitis	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Xerophthalmia	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Gastrointestinal disorders
Abdominal discomfort	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Abdominal pain	1/3 (33.3%)		0/3 (0%)		2/6 (33.3%)		0/6 (0%)		0/3 (0%)		1/3 (33.3%)		2/6 (33.3%)		0/3 (0%)		0/4 (0%)
Abdominal pain upper	0/3 (0%)		0/3 (0%)		2/6 (33.3%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Abdominal rigidity	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Anal incontinence	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Anorectal discomfort	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Aphthous ulcer	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Ascites	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Constipation	0/3 (0%)		1/3 (33.3%)		2/6 (33.3%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		1/4 (25%)
Diarrhoea	0/3 (0%)		2/3 (66.7%)		3/6 (50%)		2/6 (33.3%)		2/3 (66.7%)		0/3 (0%)		2/6 (33.3%)		1/3 (33.3%)		0/4 (0%)
Dry mouth	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Dyspepsia	0/3 (0%)		1/3 (33.3%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		1/3 (33.3%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Faecaloma	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Flatulence	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Gastrointestinal pain	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Gastrooesophageal reflux disease	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Gingival bleeding	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Haemorrhoids	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Hiatus hernia	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Melaena	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Mouth haemorrhage	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Nausea	0/3 (0%)		2/3 (66.7%)		3/6 (50%)		3/6 (50%)		0/3 (0%)		1/3 (33.3%)		2/6 (33.3%)		0/3 (0%)		0/4 (0%)
Odynophagia	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Oesophagitis	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Stomatitis	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Submaxillary gland enlargement	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Toothache	0/3 (0%)		0/3 (0%)		0/6 (0%)		2/6 (33.3%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Vomiting	0/3 (0%)		1/3 (33.3%)		3/6 (50%)		2/6 (33.3%)		0/3 (0%)		1/3 (33.3%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
General disorders
Asthenia	0/3 (0%)		0/3 (0%)		2/6 (33.3%)		3/6 (50%)		0/3 (0%)		0/3 (0%)		3/6 (50%)		0/3 (0%)		1/4 (25%)
Axillary pain	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Chest discomfort	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Chest pain	0/3 (0%)		0/3 (0%)		2/6 (33.3%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Chills	2/3 (66.7%)		2/3 (66.7%)		3/6 (50%)		3/6 (50%)		2/3 (66.7%)		2/3 (66.7%)		4/6 (66.7%)		2/3 (66.7%)		3/4 (75%)
Discomfort	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		2/3 (66.7%)		0/4 (0%)
Extravasation	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Facial pain	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Fatigue	0/3 (0%)		0/3 (0%)		2/6 (33.3%)		0/6 (0%)		1/3 (33.3%)		1/3 (33.3%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Feeling hot	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Feeling of body temperature change	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
General physical health deterioration	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Generalised oedema	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Hypothermia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Influenza like illness	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Injection site reaction	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Localised oedema	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Malaise	0/3 (0%)		0/3 (0%)		2/6 (33.3%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Mucosal inflammation	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Oedema	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Oedema peripheral	1/3 (33.3%)		1/3 (33.3%)		2/6 (33.3%)		0/6 (0%)		0/3 (0%)		1/3 (33.3%)		3/6 (50%)		0/3 (0%)		0/4 (0%)
Puncture site pain	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Pyrexia	0/3 (0%)		1/3 (33.3%)		4/6 (66.7%)		3/6 (50%)		2/3 (66.7%)		2/3 (66.7%)		3/6 (50%)		1/3 (33.3%)		2/4 (50%)
Temperature regulation disorder	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Hepatobiliary disorders
Hepatocellular injury	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		1/4 (25%)
Immune system disorders
Hypogammaglobulinaemia	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Infections and infestations
Bronchitis	1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Chronic sinusitis	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Conjunctivitis	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Device related infection	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Ear infection	1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Endocarditis bacterial	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Escherichia urinary tract infection	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Gingivitis	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Herpes virus infection	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Herpes zoster	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Influenza	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Lung infection	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Nasopharyngitis	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		2/6 (33.3%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Oral candidiasis	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Oral fungal infection	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Oral herpes	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Oral infection	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Periodontitis	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Pharyngitis	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Rhinitis	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Sinusitis	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Tonsillitis	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Tooth infection	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Upper respiratory tract infection	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Urinary tract infection	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Vulvovaginal mycotic infection	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Injury, poisoning and procedural complications
Drug administration error	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Infusion related reaction	0/3 (0%)		0/3 (0%)		4/6 (66.7%)		4/6 (66.7%)		2/3 (66.7%)		2/3 (66.7%)		5/6 (83.3%)		3/3 (100%)		4/4 (100%)
Meniscus injury	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Procedural pain	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Skin abrasion	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Transfusion reaction	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Investigations
Alanine aminotransferase increased	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		2/4 (50%)
Aspartate aminotransferase increased	0/3 (0%)		1/3 (33.3%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		2/4 (50%)
Blood alkaline phosphatase increased	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		2/4 (50%)
Blood creatinine increased	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Blood lactate dehydrogenase increased	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		1/4 (25%)
Blood phosphorus decreased	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Blood pressure increased	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Blood pressure systolic increased	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Body temperature increased	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
C-reactive protein increased	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		2/6 (33.3%)		2/3 (66.7%)		2/4 (50%)
CD4 lymphocytes decreased	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Gamma-glutamyltransferase increased	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Glomerular filtration rate decreased	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Immunoglobulins decreased	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Lymphocyte count decreased	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Lymphocyte count increased	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Oxygen saturation decreased	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		1/4 (25%)
Platelet count decreased	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Respiratory rate decreased	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
T-lymphocyte count decreased	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Vitamin B12 increased	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Weight increased	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
White blood cell count decreased	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
pH urine decreased	1/3 (33.3%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Diabetes mellitus	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Fluid overload	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Hypercalcaemia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Hyperglycaemia	0/3 (0%)		0/3 (0%)		2/6 (33.3%)		0/6 (0%)		0/3 (0%)		1/3 (33.3%)		1/6 (16.7%)		1/3 (33.3%)		1/4 (25%)
Hyperkalaemia	0/3 (0%)		1/3 (33.3%)		2/6 (33.3%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		1/3 (33.3%)		0/4 (0%)
Hyperphosphataemia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Hyperuricaemia	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		1/3 (33.3%)		0/6 (0%)		1/3 (33.3%)		1/4 (25%)
Hypoalbuminaemia	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Hypocalcaemia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		1/4 (25%)
Hypoglycaemia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		1/3 (33.3%)		0/4 (0%)
Hypokalaemia	0/3 (0%)		0/3 (0%)		2/6 (33.3%)		0/6 (0%)		0/3 (0%)		1/3 (33.3%)		0/6 (0%)		1/3 (33.3%)		2/4 (50%)
Hypophosphataemia	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Type 2 diabetes mellitus	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		1/3 (33.3%)		0/4 (0%)
Back pain	0/3 (0%)		1/3 (33.3%)		2/6 (33.3%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		3/6 (50%)		1/3 (33.3%)		0/4 (0%)
Bone pain	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Joint swelling	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Muscle spasms	0/3 (0%)		1/3 (33.3%)		1/6 (16.7%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		1/4 (25%)
Musculoskeletal pain	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Myalgia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Neck pain	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Pain in extremity	0/3 (0%)		0/3 (0%)		2/6 (33.3%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Pain in jaw	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Spinal pain	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Tendon disorder	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer	1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Melanocytic naevus	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Nervous system disorders
Ageusia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Carpal tunnel syndrome	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Cognitive disorder	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Dizziness	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Dysgeusia	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Headache	1/3 (33.3%)		0/3 (0%)		2/6 (33.3%)		1/6 (16.7%)		1/3 (33.3%)		0/3 (0%)		2/6 (33.3%)		0/3 (0%)		1/4 (25%)
Hypoaesthesia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Paraesthesia	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Polyneuropathy	0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Syncope	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Tremor	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Product Issues
Thrombosis in device	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Psychiatric disorders
Agitation	1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Confusional state	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Disorientation	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Restlessness	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Renal and urinary disorders
Haematuria	0/3 (0%)		0/3 (0%)		3/6 (50%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Pollakiuria	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Stress urinary incontinence	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Urinary incontinence	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Urinary retention	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Urinary tract pain	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Reproductive system and breast disorders
Pelvic pain	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Prostatism	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Uterine polyp	1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Atelectasis	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Bronchospasm	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Cough	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		2/6 (33.3%)		0/3 (0%)		0/3 (0%)		2/6 (33.3%)		1/3 (33.3%)		1/4 (25%)
Dysphonia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Dyspnoea	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		1/6 (16.7%)		2/3 (66.7%)		0/3 (0%)		3/6 (50%)		1/3 (33.3%)		0/4 (0%)
Dyspnoea exertional	0/3 (0%)		0/3 (0%)		2/6 (33.3%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Epistaxis	0/3 (0%)		0/3 (0%)		2/6 (33.3%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Haemoptysis	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Hypoxia	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Nasal congestion	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Oropharyngeal pain	1/3 (33.3%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Pleural effusion	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Productive cough	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Rales	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Rhinorrhoea	0/3 (0%)		0/3 (0%)		2/6 (33.3%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Throat tightness	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Wheezing	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Skin and subcutaneous tissue disorders
Actinic keratosis	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Blister	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Ecchymosis	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Erythema	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Hyperhidrosis	1/3 (33.3%)		0/3 (0%)		2/6 (33.3%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		2/3 (66.7%)		2/4 (50%)
Night sweats	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/3 (0%)		1/3 (33.3%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Penile ulceration	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Petechiae	0/3 (0%)		0/3 (0%)		2/6 (33.3%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)		0/4 (0%)
Pruritus	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Rash	1/3 (33.3%)		1/3 (33.3%)		0/6 (0%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Skin lesion	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Vascular disorders
Flushing	0/3 (0%)		0/3 (0%)		0/6 (0%)		1/6 (16.7%)		1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Haematoma	1/3 (33.3%)		1/3 (33.3%)		2/6 (33.3%)		1/6 (16.7%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Hot flush	1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)		0/4 (0%)
Hypertension	0/3 (0%)		1/3 (33.3%)		1/6 (16.7%)		0/6 (0%)		1/3 (33.3%)		0/3 (0%)		3/6 (50%)		1/3 (33.3%)		1/4 (25%)
Hypotension	0/3 (0%)		0/3 (0%)		3/6 (50%)		1/6 (16.7%)		1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Pallor	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		1/4 (25%)
Phlebitis	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		1/3 (33.3%)		0/4 (0%)
Thrombophlebitis	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)
Thrombosis	0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/6 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)		0/4 (0%)

Limitations/Caveats

The trial was discontinued due to lack of recruitment before a formal maximum tolerated dose (MTD) was established based on the number of patients with Dose Limiting Toxicities (DLTs) in the first treatment cycle.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.