Trial Outcomes & Findings for Phase 1 Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of H3B-6527 in Participants With Advanced Hepatocellular Carcinoma (NCT NCT02834780)

Last Updated: 2023-11-13

Results Overview

DLTs were defined as any of the following toxicities: Hematology, gastrointestinal, renal, hepatic or nonhematologic toxicities occurring during Cycle 1 in Dose Escalation Phase only and judged by the investigator as related to study drug. This included any Grade 4: neutropenia that does not resolve to Grade less than or equal to (\<=) 2 within 7 days, thrombocytopenia, anemia of any duration, diarrhea and/or vomiting irrespective of prophylaxis or appropriate treatment; Grade 3: thrombocytopenia requiring transfusion, thrombocytopenia and clinically significant bleeding, anemia if transfused or if lasting for more than 7 days, nausea, vomiting and/or diarrhea lasting more than 72 hours despite the use of optimal anti-emetic/antidiarrheal treatment, bilirubin, fatigue lasting less than 1 week, elevations in biochemistry laboratory values without associated clinical symptoms that last for \<=7 days; Grade greater than or equal to (\>=) 3 serum creatinine.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

128 participants

Primary outcome timeframe

Cycle 1 (Cycle length = 21 days)

Results posted on

2023-11-13

Participant Flow

Participants took part in the study at 54 investigative sites in Belgium, Canada, France, Italy, Republic of Korea, Russian Federation, Singapore, Spain, Taiwan and the United States from 28 December 2016 to 23 February 2022.

A total of 304 participants were screened, of which 176 were screen failures and 128 were enrolled into two parts: Dose Escalation Phase (Part 1) and Dose Expansion Phase (Part 2) to receive study treatment.

Participant milestones

Participant milestones
Measure	Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted Participants received H3B-6527 300 milligram (mg) capsule, orally, once daily (QD) in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed Participants received H3B-6527 2000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted Participants received H3B-6527 500 mg capsule, orally, twice a day (BID) in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed Participants received H3B-6527 700 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle either in fasted or fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.
Overall Study STARTED	3	3	4	10	3	7	4	7	3	10	5	29	40
Overall Study COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	3	3	4	10	3	7	4	7	3	10	5	29	40

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted Participants received H3B-6527 300 milligram (mg) capsule, orally, once daily (QD) in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed Participants received H3B-6527 2000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted Participants received H3B-6527 500 mg capsule, orally, twice a day (BID) in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed Participants received H3B-6527 700 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle either in fasted or fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.
Overall Study Disease Progression -Radiologically Confirmed	1	3	2	7	1	6	2	4	3	6	3	24	32
Overall Study Withdrawal by Subject	0	0	1	0	0	0	0	0	0	0	1	0	0
Overall Study Adverse Event	0	0	0	0	1	0	1	1	0	2	0	3	2
Overall Study Disease Progression - Clinically Confirmed	1	0	0	1	1	1	1	2	0	2	1	2	5
Overall Study Other	1	0	1	2	0	0	0	0	0	0	0	0	1

Baseline Characteristics

Phase 1 Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of H3B-6527 in Participants With Advanced Hepatocellular Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted n=3 Participants Participants received H3B-6527 300 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted n=3 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed n=4 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted n=10 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed n=3 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted n=7 Participants Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed n=4 Participants Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed n=7 Participants Participants received H3B-6527 2000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted n=3 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed n=10 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed n=5 Participants Participants received H3B-6527 700 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD n=29 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle either in fasted or fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed n=40 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Total n=128 Participants Total of all reporting groups
Age, Continuous	59.0 years STANDARD_DEVIATION 7.00 • n=5 Participants	72.7 years STANDARD_DEVIATION 4.73 • n=7 Participants	68.5 years STANDARD_DEVIATION 9.75 • n=5 Participants	67.1 years STANDARD_DEVIATION 8.01 • n=4 Participants	68.7 years STANDARD_DEVIATION 6.51 • n=21 Participants	59.3 years STANDARD_DEVIATION 12.22 • n=8 Participants	60.3 years STANDARD_DEVIATION 7.14 • n=8 Participants	62.1 years STANDARD_DEVIATION 7.52 • n=24 Participants	68.7 years STANDARD_DEVIATION 4.04 • n=42 Participants	62.0 years STANDARD_DEVIATION 16.51 • n=42 Participants	65.6 years STANDARD_DEVIATION 9.91 • n=42 Participants	61.4 years STANDARD_DEVIATION 10.67 • n=42 Participants	64.3 years STANDARD_DEVIATION 10.58 • n=36 Participants	63.6 years STANDARD_DEVIATION 10.50 • n=36 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	0 Participants n=21 Participants	3 Participants n=8 Participants	2 Participants n=8 Participants	3 Participants n=24 Participants	1 Participants n=42 Participants	3 Participants n=42 Participants	2 Participants n=42 Participants	7 Participants n=42 Participants	12 Participants n=36 Participants	37 Participants n=36 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants	3 Participants n=21 Participants	4 Participants n=8 Participants	2 Participants n=8 Participants	4 Participants n=24 Participants	2 Participants n=42 Participants	7 Participants n=42 Participants	3 Participants n=42 Participants	22 Participants n=42 Participants	28 Participants n=36 Participants	91 Participants n=36 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants	2 Participants n=36 Participants	5 Participants n=36 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants	3 Participants n=21 Participants	7 Participants n=8 Participants	4 Participants n=8 Participants	6 Participants n=24 Participants	3 Participants n=42 Participants	9 Participants n=42 Participants	5 Participants n=42 Participants	27 Participants n=42 Participants	28 Participants n=36 Participants	111 Participants n=36 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants	10 Participants n=36 Participants	12 Participants n=36 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=8 Participants	2 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	5 Participants n=42 Participants	2 Participants n=42 Participants	8 Participants n=42 Participants	7 Participants n=36 Participants	30 Participants n=36 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=8 Participants	1 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	1 Participants n=36 Participants	5 Participants n=36 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	9 Participants n=4 Participants	1 Participants n=21 Participants	4 Participants n=8 Participants	1 Participants n=8 Participants	7 Participants n=24 Participants	3 Participants n=42 Participants	4 Participants n=42 Participants	3 Participants n=42 Participants	20 Participants n=42 Participants	22 Participants n=36 Participants	81 Participants n=36 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=36 Participants	1 Participants n=36 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants	10 Participants n=36 Participants	11 Participants n=36 Participants

PRIMARY outcome

Timeframe: Cycle 1 (Cycle length = 21 days)

Population: DLT analysis set included all participants in Dose Escalation phase (Part 1) who must have completed safety assessments through pre-dose on Cycle 2 Day 1 and must have received at least 17 of 21 (approximately 80 percent \[%\]) study days within Cycle 1, unless due to a DLT. This outcome measure was planned to be analyzed for Part 1 only.

Outcome measures

Outcome measures
Measure	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted n=3 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed n=9 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed n=4 Participants Participants received H3B-6527 700 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted n=3 Participants Participants received H3B-6527 300 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted n=3 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed n=4 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted n=10 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed n=3 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted n=6 Participants Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed n=3 Participants Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed n=7 Participants Participants received H3B-6527 2000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle either in fasted or fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.
Part 1, Dose Escalation Phase: Number of Participants With Dose-limiting Toxicities (DLTs) Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—

PRIMARY outcome

Timeframe: From the first dose of study drug up to approximately 36.7 months

Population: Safety analysis set included all participants who received at least 1 dose of the study drug. This outcome measure was planned to be analyzed for Part 1 and Part 2.

A TEAE was defined as an adverse event (AE) that emerges during treatment, having been absent at pretreatment (Baseline) or reemerges during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsens in severity during treatment relative to the pretreatment state, when the AE was continuous. An SAE was any untoward medical occurrence that at any dose: Resulted in death, was life-threatening (that is, the participant was at immediate risk of death from the AE as it occurred; this does not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug).

Outcome measures

Outcome measures
Measure	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted n=3 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed n=10 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed n=5 Participants Participants received H3B-6527 700 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted n=3 Participants Participants received H3B-6527 300 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted n=3 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed n=4 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted n=10 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed n=3 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted n=7 Participants Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed n=4 Participants Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed n=7 Participants Participants received H3B-6527 2000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD n=29 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle either in fasted or fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed n=40 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Participants with TEAEs	3 Participants	9 Participants	5 Participants	3 Participants	3 Participants	4 Participants	10 Participants	3 Participants	7 Participants	4 Participants	7 Participants	28 Participants	40 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Participants with SAEs	2 Participants	3 Participants	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants	4 Participants	1 Participants	2 Participants	11 Participants	17 Participants

PRIMARY outcome

Timeframe: From baseline up to approximately 36.7 months

Population: Safety analysis set included all participants who received at least 1 dose of the study drug. This outcome measure was planned to be analyzed for Part 1 and Part 2.

Laboratory assessment included hematology, coagulation, clinical chemistry, and urinalysis parameters.

Outcome measures

Outcome measures
Measure	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted n=3 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed n=10 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed n=5 Participants Participants received H3B-6527 700 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted n=3 Participants Participants received H3B-6527 300 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted n=3 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed n=4 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted n=10 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed n=3 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted n=7 Participants Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed n=4 Participants Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed n=7 Participants Participants received H3B-6527 2000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD n=29 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle either in fasted or fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed n=40 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.
Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters Hematology	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters Clinical Chemistry	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters Urinalysis	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters Coagulation	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From baseline up to approximately 36.7 months

Population: Safety analysis set included all participants who received at least 1 dose of the study drug. This outcome measure was planned to be analyzed for Part 1 and Part 2.

Outcome measures

Outcome measures
Measure	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted n=3 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed n=10 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed n=5 Participants Participants received H3B-6527 700 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted n=3 Participants Participants received H3B-6527 300 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted n=3 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed n=4 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted n=10 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed n=3 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted n=7 Participants Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed n=4 Participants Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed n=7 Participants Participants received H3B-6527 2000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD n=29 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle either in fasted or fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed n=40 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.
Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From baseline up to approximately 36.7 months

Population: Safety analysis set included all participants who received at least 1 dose of the study drug. This outcome measure was planned to be analyzed for Part 1 and Part 2.

Outcome measures

Outcome measures
Measure	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted n=3 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed n=10 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed n=5 Participants Participants received H3B-6527 700 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted n=3 Participants Participants received H3B-6527 300 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted n=3 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed n=4 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted n=10 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed n=3 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted n=7 Participants Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed n=4 Participants Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed n=7 Participants Participants received H3B-6527 2000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD n=29 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle either in fasted or fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed n=40 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.
Number of Participants With Clinically Significant Change From Baseline in Vital Sign Parameters	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Part 1, Cycle 1 Day 1 and Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing); Part 2, Cycle 1 Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing) (Cycle 1 length = 21 days)

Population: Pharmacokinetic (PK) analysis set: Participants who received at least 1 dose of study drug and had at least 1 evaluable plasma concentration. 'Overall Number of participants analyzed' signifies those who were evaluable for this outcome measure; 'Number analyzed' signifies participants who were evaluable at given timepoints. As planned, PK data was collected and reported together due to same dose and food conditions in Part 1 and 2 for H3B-6527 1000 mg (QD fed and fasted) and 500 mg (BID fed).

Outcome measures

Outcome measures
Measure	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted n=3 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed n=45 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed n=5 Participants Participants received H3B-6527 700 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted n=3 Participants Participants received H3B-6527 300 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted n=3 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed n=4 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted n=32 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed n=7 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted n=7 Participants Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed n=4 Participants Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed n=7 Participants Participants received H3B-6527 2000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle either in fasted or fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.
Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 Cycle 1 Day 1	462 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 137.0	752 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 204.3	576 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 482.6	68.9 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 57.5	173 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 1891.9	1631 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 271.8	850 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 531.5	1115 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 909.7	400 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 187.5	5671 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 98.7	2748 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 66.3	—	—
Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 Cycle 1 Day 8	1056 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 36.9	809 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 237.3	622 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 351.1	50.8 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 47.5	636 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 39.4	484 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 3217.3	784 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 431.8	798 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 337.8	1244 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 827.7	5447 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 74.9	1838 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 179.3	—	—

SECONDARY outcome

Population: PK analysis set: Participants who received at least 1 dose of study drug and had at least 1 evaluable plasma concentration. 'Overall Number of participants analyzed' signifies those who were evaluable for this outcome measure; 'Number analyzed' signifies participants who were evaluable at given timepoints. As planned, PK data was collected and reported together due to same dose and food conditions in Part 1 and 2 for H3B-6527 1000 mg (QD fed and fasted) and 500 mg (BID fed).

Outcome measures

Outcome measures
Measure	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted n=3 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed n=45 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed n=5 Participants Participants received H3B-6527 700 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted n=3 Participants Participants received H3B-6527 300 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted n=3 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed n=4 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted n=32 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed n=7 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted n=7 Participants Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed n=4 Participants Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed n=7 Participants Participants received H3B-6527 2000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle either in fasted or fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.
Maximum Observed Plasma Concentration (Cmax) of H3B-6527 Cycle 1 Day 1	124 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 159.1	255 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 251.6	163 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 303.2	20.3 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 64.1	74.5 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 1389.4	395 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 133.7	225 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 470.2	182 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 494.6	136 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 429.4	904 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 34.2	540 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 79.9	—	—
Maximum Observed Plasma Concentration (Cmax) of H3B-6527 Cycle 1 Day 8	251 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 46.5	211 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 237.2	167 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 202.7	10.8 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 90.6	194 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 45.6	99.6 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 5300.4	187 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 339.1	177 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 370.3	362 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 898.5	827 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 40.6	502 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 95.2	—	—

SECONDARY outcome

Outcome measures

Outcome measures
Measure	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted n=3 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed n=45 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed n=5 Participants Participants received H3B-6527 700 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted n=3 Participants Participants received H3B-6527 300 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted n=3 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed n=4 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted n=32 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed n=7 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted n=7 Participants Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed n=4 Participants Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed n=7 Participants Participants received H3B-6527 2000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle either in fasted or fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.
Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 Cycle 1 Day 8	4.00 hours Interval 2.1 to 4.17	4.00 hours Interval 0.0 to 10.0	4.12 hours Interval 0.5 to 10.0	4.00 hours Interval 2.07 to 4.0	0.52 hours Interval 0.5 to 2.0	4.52 hours Interval 0.53 to 6.0	2.00 hours Interval 0.33 to 10.0	2.00 hours Interval 1.0 to 4.33	2.10 hours Interval 1.0 to 4.13	5.86 hours Interval 2.0 to 6.22	4.00 hours Interval 1.0 to 8.42	—	—
Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527 Cycle 1 Day 1	2.12 hours Interval 2.0 to 4.57	4.02 hours Interval 0.57 to 10.0	2.02 hours Interval 0.5 to 6.12	2.00 hours Interval 2.0 to 4.0	1.00 hours Interval 0.5 to 2.0	4.00 hours Interval 1.0 to 4.07	2.02 hours Interval 1.0 to 8.12	6.00 hours Interval 4.1 to 6.0	1.00 hours Interval 0.63 to 4.15	5.00 hours Interval 2.0 to 8.0	2.100 hours Interval 1.0 to 4.92	—	—

SECONDARY outcome

Timeframe: From the first dose date until disease progression/recurrence or up to approximately 36.7 months

Population: Full analysis set included all participants who received at least 1 dose of the study drug. Here, "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. This outcome measure was planned to be analyzed for Part 2 only.

ORR was defined as the percentage of participants achieving a best overall confirmed response of partial response (PR) or complete response (CR) (PR + CR), from the first dose date until disease progression/recurrence. Responses (PR or CR) were confirmed no less than 4 weeks after the initial response. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in the short axis to less than 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The tumor assessment was done using number of lesions based on modified RECIST v1.1 for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ.

Outcome measures

Outcome measures
Measure	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed Participants received H3B-6527 700 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted n=18 Participants Participants received H3B-6527 300 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted n=32 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed Participants received H3B-6527 2000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle either in fasted or fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.
Part 2, Dose Expansion Phase: Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1	—	—	—	5.6 percentage of participants Interval 0.1 to 27.3	0.0 percentage of participants Interval 0.0 to 10.9	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From the date of first documented CR or PR up to approximately 36.7 months

Population: Full analysis set included all participants who received at least 1 dose of the study drug. Here, overall number of participants analyzed "N" included the participants who had CR or PR. This outcome measure was planned to be analyzed for Part 2 only.

DOR was defined as the time from the date of first documented CR or PR based on modified RECIST v1.1 until the first documentation of disease progression (PD) as determined by the investigator or death, whichever comes first. CR was defined as the disappearance of all target lesions and non-target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of long diameter (LD) of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).

Outcome measures

Outcome measures
Measure	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed Participants received H3B-6527 700 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted n=1 Participants Participants received H3B-6527 300 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed Participants received H3B-6527 2000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle either in fasted or fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.
Part 2, Dose Expansion Phase: Duration of Response (DOR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1	—	—	—	NA months The DOR could not be evaluated due to the small number of responders participants.	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From the first dose date to the date of the first documentation of PD as determined by the investigator or death (whichever occurs first) up to approximately 36.7 months

PFS was defined as the time from the first dose date to the date of the first documentation of PD as determined by the investigator or death (whichever occurs first). PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).

Outcome measures

Outcome measures
Measure	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed Participants received H3B-6527 700 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted n=18 Participants Participants received H3B-6527 300 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted n=32 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed Participants received H3B-6527 2000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle either in fasted or fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.
Part 2, Dose Expansion Phase: Progression-free Survival (PFS) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1	—	—	—	2.6 months Interval 1.3 to 5.5	3.0 months Interval 1.5 to 4.1	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From the date of first dose of study drug until date of death from any cause (up to approximately 36.7 months)

OS was defined as the time from the first dose date to the date of death. OS was assessed using Kaplan-Meier method. The time of death was censored for participants who were without death information at the time of OS analysis.

Outcome measures

Outcome measures
Measure	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed Participants received H3B-6527 700 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted n=18 Participants Participants received H3B-6527 300 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted n=32 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed Participants received H3B-6527 2000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle either in fasted or fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.
Part 2, Dose Expansion Phase: Overall Survival (OS)	—	—	—	9.5 months Interval 2.3 to 24.4	7.7 months Interval 4.7 to 11.3	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From date of first dose of study drug until CR or PR (up to approximately 36.7 months)

Population: Full analysis set included all participants who received at least 1 dose of the study drug. Here, "overall number of participants analyzed" signifies participants who had CR or PR. This outcome measure was planned to be analyzed for Part 2 only.

TTR was defined as the time from the first dose date to the date of first documented CR/PR. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in the short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Outcome measures
Measure	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed Participants received H3B-6527 700 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted n=1 Participants Participants received H3B-6527 300 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed Participants received H3B-6527 2000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle either in fasted or fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.
Part 2, Dose Expansion Phase: Time to Response (TTR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1	—	—	—	NA months The TTR could not be evaluated due to the small number of responders participants.	—	—	—	—	—	—	—	—	—

Adverse Events

Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted

Serious events: 0 serious events

Other events: 3 other events

Deaths: 1 deaths

Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted

Serious events: 0 serious events

Other events: 3 other events

Deaths: 3 deaths

Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed

Serious events: 1 serious events

Other events: 4 other events

Deaths: 2 deaths

Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted

Serious events: 1 serious events

Other events: 10 other events

Deaths: 6 deaths

Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed

Serious events: 1 serious events

Other events: 3 other events

Deaths: 2 deaths

Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted

Serious events: 4 serious events

Other events: 7 other events

Deaths: 7 deaths

Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed

Serious events: 1 serious events

Other events: 4 other events

Deaths: 3 deaths

Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed

Serious events: 2 serious events

Other events: 7 other events

Deaths: 1 deaths

Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted

Serious events: 2 serious events

Other events: 3 other events

Deaths: 3 deaths

Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed

Serious events: 3 serious events

Other events: 9 other events

Deaths: 6 deaths

Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed

Serious events: 1 serious events

Other events: 5 other events

Deaths: 4 deaths

Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD

Serious events: 11 serious events

Other events: 28 other events

Deaths: 19 deaths

Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed

Serious events: 17 serious events

Other events: 39 other events

Deaths: 31 deaths

Serious adverse events

Serious adverse events
Measure	Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted n=3 participants at risk Participants received H3B-6527 300 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted n=3 participants at risk Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed n=4 participants at risk Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted n=10 participants at risk Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed n=3 participants at risk Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted n=7 participants at risk Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed n=4 participants at risk Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed n=7 participants at risk Participants received H3B-6527 2000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted n=3 participants at risk Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed n=10 participants at risk Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed n=5 participants at risk Participants received H3B-6527 700 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD n=29 participants at risk Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle either in fasted or fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed n=40 participants at risk Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Abdominal pain upper	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Oesophageal varices haemorrhage	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months
General disorders Asthenia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	28.6% 2/7 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months
Hepatobiliary disorders Hepatic haemorrhage	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Immune system disorders Anaphylactic reaction	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Infections and infestations Abdominal sepsis	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Injury, poisoning and procedural complications Post procedural complication	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Investigations Electrocardiogram QT prolonged	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	5.0% 2/40 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months
Nervous system disorders Hepatic encephalopathy	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Renal and urinary disorders Acute kidney injury	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Vascular disorders Peripheral embolism	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Constipation	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	7.5% 3/40 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour rupture	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Nervous system disorders Cerebrovascular accident	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Blood and lymphatic system disorders Immune thrombocytopenia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Cardiac disorders Acute coronary syndrome	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Ascites	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	7.5% 3/40 • Number of events 4 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Duodenal ulcer	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Gastritis	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Varices oesophageal	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Vomiting	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months
General disorders General physical health deterioration	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months
General disorders Incarcerated hernia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
General disorders Peripheral swelling	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Hepatobiliary disorders Cholangitis	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months
Hepatobiliary disorders Hepatic cirrhosis	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Hepatobiliary disorders Hepatic failure	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Hepatobiliary disorders Jaundice	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Infections and infestations Pneumonia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	6.9% 2/29 • Number of events 5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Infections and infestations Pulmonary sepsis	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months
Investigations Blood bilirubin increased	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Investigations White blood cell count increased	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Investigations Dehydration	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Musculoskeletal and connective tissue disorders Pathological fracture	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	5.0% 2/40 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant ascites	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months

Other adverse events

Other adverse events
Measure	Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted n=3 participants at risk Participants received H3B-6527 300 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted n=3 participants at risk Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed n=4 participants at risk Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted n=10 participants at risk Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed n=3 participants at risk Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted n=7 participants at risk Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed n=4 participants at risk Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed n=7 participants at risk Participants received H3B-6527 2000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted n=3 participants at risk Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed n=10 participants at risk Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed n=5 participants at risk Participants received H3B-6527 700 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD n=29 participants at risk Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle either in fasted or fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed n=40 participants at risk Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.
Hepatobiliary disorders Hepatomegaly	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Hepatobiliary disorders Hepatorenal syndrome	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Hepatobiliary disorders Hepatitis	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Hepatobiliary disorders Hyperbilirubinaemia	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months
Hepatobiliary disorders Portal vein thrombosis	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Infections and infestations Gingivitis	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Infections and infestations Nasopharyngitis	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Infections and infestations Peritonitis bacterial	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Infections and infestations Pneumonia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Infections and infestations Sinusitis	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Infections and infestations Upper respiratory tract infection	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Injury, poisoning and procedural complications Breast injury	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Injury, poisoning and procedural complications Contusion	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Injury, poisoning and procedural complications Fall	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	5.0% 2/40 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months
Investigations Human metapneumovirus test positive	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Injury, poisoning and procedural complications Intentional overdose	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Investigations International normalised ratio increased	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Injury, poisoning and procedural complications Muscle strain	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Investigations Activated partial thromboplastin time shortened	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Investigations Alanine aminotransferase increased	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	66.7% 2/3 • Number of events 4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	20.0% 2/10 • Number of events 5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	28.6% 2/7 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	57.1% 4/7 • Number of events 6 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	20.0% 2/10 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	40.0% 2/5 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	25.0% 10/40 • Number of events 24 • From the first dose of study drug up to approximately 36.7 months
Investigations Aspartate aminotransferase increased	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	66.7% 2/3 • Number of events 4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	20.0% 2/10 • Number of events 15 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	28.6% 2/7 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	50.0% 2/4 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	57.1% 4/7 • Number of events 10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	40.0% 2/5 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	6.9% 2/29 • Number of events 7 • From the first dose of study drug up to approximately 36.7 months	35.0% 14/40 • Number of events 34 • From the first dose of study drug up to approximately 36.7 months
Investigations Blood alkaline phosphatase increased	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	42.9% 3/7 • Number of events 7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 4 • From the first dose of study drug up to approximately 36.7 months	6.9% 2/29 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 11 • From the first dose of study drug up to approximately 36.7 months
Investigations Blood bilirubin increased	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	42.9% 3/7 • Number of events 5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	42.9% 3/7 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	6.9% 2/29 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	22.5% 9/40 • Number of events 21 • From the first dose of study drug up to approximately 36.7 months
Investigations Blood cholesterol increased	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Investigations Blood creatinine increased	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 8 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Investigations Blood glucose increased	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Investigations Blood potassium increased	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Investigations Blood uric acid increased	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Investigations Blood urine present	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Investigations Gamma-glutamyltransferase increased	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	5.0% 2/40 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months
Investigations Haemoglobin decreased	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Metabolism and nutrition disorders Hyperphosphataemia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months
Metabolism and nutrition disorders Hypertriglyceridaemia	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	10.0% 4/40 • Number of events 6 • From the first dose of study drug up to approximately 36.7 months
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	28.6% 2/7 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months
Investigations Platelet count decreased	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	6.9% 2/29 • Number of events 4 • From the first dose of study drug up to approximately 36.7 months	10.0% 4/40 • Number of events 4 • From the first dose of study drug up to approximately 36.7 months
Investigations Total bile acids increased	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months
Investigations Transaminases increased	33.3% 1/3 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	20.0% 2/10 • Number of events 9 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	6.9% 2/29 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	7.5% 3/40 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months
Investigations Waist circumference increased	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Investigations Weight decreased	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	28.6% 2/7 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	6.9% 2/29 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	7.5% 3/40 • Number of events 8 • From the first dose of study drug up to approximately 36.7 months
Metabolism and nutrition disorders Decreased appetite	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	28.6% 2/7 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	20.0% 2/10 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	13.8% 4/29 • Number of events 7 • From the first dose of study drug up to approximately 36.7 months	27.5% 11/40 • Number of events 13 • From the first dose of study drug up to approximately 36.7 months
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	28.6% 2/7 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Metabolism and nutrition disorders Hyperglycaemia	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	28.6% 2/7 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	5.0% 2/40 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months
Metabolism and nutrition disorders Hyperkalaemia	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 24 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	28.6% 2/7 • Number of events 15 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Metabolism and nutrition disorders Hypernatraemia	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Musculoskeletal and connective tissue disorders Muscle tightness	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	5.0% 2/40 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	30.0% 3/10 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	10.0% 4/40 • Number of events 4 • From the first dose of study drug up to approximately 36.7 months
Musculoskeletal and connective tissue disorders Coccydynia	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant ascites	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	7.5% 3/40 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Nervous system disorders Taste disorder	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Psychiatric disorders Depression	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Psychiatric disorders Insomnia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months
Renal and urinary disorders Acute kidney injury	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	28.6% 2/7 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Renal and urinary disorders Proteinuria	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	6.9% 2/29 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	7.5% 3/40 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months
Respiratory, thoracic and mediastinal disorders Dry throat	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour invasion	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Nervous system disorders Aphasia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Nervous system disorders Dizziness	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Nervous system disorders Headache	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	20.0% 2/10 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months
Nervous system disorders Hyperaesthesia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months
Nervous system disorders Hypoaesthesia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Nervous system disorders Lethargy	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Nervous system disorders Paraesthesia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Nervous system disorders Somnolence	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	50.0% 2/4 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	20.0% 2/10 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	10.0% 4/40 • Number of events 4 • From the first dose of study drug up to approximately 36.7 months
Skin and subcutaneous tissue disorders Rash	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Skin and subcutaneous tissue disorders Skin plaque	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Vascular disorders Hypotension	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Endocrine disorders Hypothyroidism	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Eye disorders Visual impairment	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Oral dysaesthesia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Toothache	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
General disorders Chills	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Hepatobiliary disorders Jaundice	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Investigations Activated partial thromboplastin time prolonged	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	7.5% 3/40 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Skin and subcutaneous tissue disorders Erythema	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to eye	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Renal and urinary disorders Choluria	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Renal and urinary disorders Pollakiuria	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Hepatobiliary disorders Hepatocellular injury	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	15.0% 6/40 • Number of events 6 • From the first dose of study drug up to approximately 36.7 months
Infections and infestations Urinary tract infection	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	6.9% 2/29 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months
Injury, poisoning and procedural complications Procedural pain	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	10.3% 3/29 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Vascular disorders Hypertension	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	7.5% 3/40 • Number of events 6 • From the first dose of study drug up to approximately 36.7 months
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	13.8% 4/29 • Number of events 4 • From the first dose of study drug up to approximately 36.7 months	7.5% 3/40 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Musculoskeletal and connective tissue disorders Pathological fracture	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
General disorders Pyrexia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	13.8% 4/29 • Number of events 5 • From the first dose of study drug up to approximately 36.7 months	5.0% 2/40 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months
Blood and lymphatic system disorders Anaemia	66.7% 2/3 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	42.9% 3/7 • Number of events 4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	28.6% 2/7 • Number of events 4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	10.0% 4/40 • Number of events 7 • From the first dose of study drug up to approximately 36.7 months
Blood and lymphatic system disorders Leukopenia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	28.6% 2/7 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	5.0% 2/40 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Blood and lymphatic system disorders Lymphopenia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	28.6% 2/7 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	7.5% 3/40 • Number of events 7 • From the first dose of study drug up to approximately 36.7 months
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	28.6% 2/7 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	5.0% 2/40 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months
Cardiac disorders Atrial fibrillation	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	3.4% 1/29 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months
Cardiac disorders Sinus tachycardia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Cardiac disorders Supraventricular extrasystoles	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Cardiac disorders Tachycardia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Cardiac disorders Ventricular extrasystoles	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Ear and labyrinth disorders Deafness	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Eye disorders Blepharitis	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Eye disorders Cataract	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Eye disorders Cataract nuclear	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Eye disorders Chalazion	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Eye disorders Conjunctivitis allergic	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Eye disorders Corneal thinning	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Eye disorders Keratitis	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Eye disorders Open angle glaucoma	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Eye disorders Periorbital oedema	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Eye disorders Retinal haemorrhage	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Eye disorders Swelling of eyelid	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Abdominal distension	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	6.9% 2/29 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	7.5% 3/40 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	50.0% 2/4 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	28.6% 2/7 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	28.6% 2/7 • Number of events 4 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	17.2% 5/29 • Number of events 6 • From the first dose of study drug up to approximately 36.7 months	22.5% 9/40 • Number of events 9 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Abdominal pain upper	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	6.9% 2/29 • Number of events 4 • From the first dose of study drug up to approximately 36.7 months	7.5% 3/40 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Ascites	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Constipation	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	28.6% 2/7 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	40.0% 2/5 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	13.8% 4/29 • Number of events 7 • From the first dose of study drug up to approximately 36.7 months	7.5% 3/40 • Number of events 6 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Diarrhoea	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 4 • From the first dose of study drug up to approximately 36.7 months	75.0% 3/4 • Number of events 4 • From the first dose of study drug up to approximately 36.7 months	70.0% 7/10 • Number of events 13 • From the first dose of study drug up to approximately 36.7 months	66.7% 2/3 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	57.1% 4/7 • Number of events 6 • From the first dose of study drug up to approximately 36.7 months	50.0% 2/4 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	57.1% 4/7 • Number of events 10 • From the first dose of study drug up to approximately 36.7 months	66.7% 2/3 • Number of events 5 • From the first dose of study drug up to approximately 36.7 months	60.0% 6/10 • Number of events 6 • From the first dose of study drug up to approximately 36.7 months	60.0% 3/5 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	34.5% 10/29 • Number of events 22 • From the first dose of study drug up to approximately 36.7 months	67.5% 27/40 • Number of events 45 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Dry mouth	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	6.9% 2/29 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	2.5% 1/40 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Faeces discoloured	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Gingival bleeding	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Haemorrhoids	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Nausea	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 4 • From the first dose of study drug up to approximately 36.7 months	40.0% 4/10 • Number of events 7 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	57.1% 4/7 • Number of events 5 • From the first dose of study drug up to approximately 36.7 months	50.0% 2/4 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	57.1% 4/7 • Number of events 7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	20.0% 2/10 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	20.7% 6/29 • Number of events 7 • From the first dose of study drug up to approximately 36.7 months	20.0% 8/40 • Number of events 10 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Vomiting	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	30.0% 3/10 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	57.1% 4/7 • Number of events 6 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	42.9% 3/7 • Number of events 11 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	17.2% 5/29 • Number of events 6 • From the first dose of study drug up to approximately 36.7 months	10.0% 4/40 • Number of events 9 • From the first dose of study drug up to approximately 36.7 months
Gastrointestinal disorders Paraesthesia oral	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
General disorders Asthenia	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	28.6% 2/7 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	20.0% 2/10 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	20.0% 1/5 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	17.2% 5/29 • Number of events 9 • From the first dose of study drug up to approximately 36.7 months	15.0% 6/40 • Number of events 8 • From the first dose of study drug up to approximately 36.7 months
General disorders Cyst	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/29 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/40 • From the first dose of study drug up to approximately 36.7 months
General disorders Fatigue	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	28.6% 2/7 • Number of events 3 • From the first dose of study drug up to approximately 36.7 months	50.0% 2/4 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	57.1% 4/7 • Number of events 8 • From the first dose of study drug up to approximately 36.7 months	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	40.0% 2/5 • Number of events 2 • From the first dose of study drug up to approximately 36.7 months	10.3% 3/29 • Number of events 5 • From the first dose of study drug up to approximately 36.7 months	22.5% 9/40 • Number of events 14 • From the first dose of study drug up to approximately 36.7 months
General disorders Oedema peripheral	33.3% 1/3 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/4 • From the first dose of study drug up to approximately 36.7 months	10.0% 1/10 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	28.6% 2/7 • Number of events 4 • From the first dose of study drug up to approximately 36.7 months	25.0% 1/4 • Number of events 1 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/7 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/3 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/10 • From the first dose of study drug up to approximately 36.7 months	0.00% 0/5 • From the first dose of study drug up to approximately 36.7 months	10.3% 3/29 • Number of events 7 • From the first dose of study drug up to approximately 36.7 months	12.5% 5/40 • Number of events 6 • From the first dose of study drug up to approximately 36.7 months

Additional Information

Eisai Medical Information

Eisai Inc.

Phone: 1-888-274-2378

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fasted n=3 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 500 mg BID Fed n=45 Participants Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 700 mg BID Fed n=5 Participants Participants received H3B-6527 700 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 300 mg QD Fasted n=3 Participants Participants received H3B-6527 300 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fasted n=3 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 600 mg QD Fed n=4 Participants Participants received H3B-6527 600 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fasted n=32 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1000 mg QD Fed n=7 Participants Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fasted n=7 Participants Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fasted state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 1400 mg QD Fed n=4 Participants Participants received H3B-6527 1400 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 1, Dose Escalation Phase: H3B-6527 2000 mg QD Fed n=7 Participants Participants received H3B-6527 2000 mg capsule, orally, QD in 21-days cycle in fed state during treatment phase in dose escalation phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 1000 mg QD Participants received H3B-6527 1000 mg capsule, orally, QD in 21-days cycle either in fasted or fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.	Part 2, Dose Expansion Phase: H3B-6527 500 mg BID Fed Participants received H3B-6527 500 mg capsule, orally, BID in 21-days cycle in fed state during treatment phase in dose expansion phase until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the participants from the study by the Sponsor.
Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 Cycle 1 Day 1	462 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 137.0	752 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 204.3	576 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 482.6	68.9 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 57.5	173 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 1891.9	1631 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 271.8	850 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 531.5	1115 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 909.7	400 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 187.5	5671 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 98.7	2748 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 66.3	—	—
Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527 Cycle 1 Day 8	1056 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 36.9	809 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 237.3	622 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 351.1	50.8 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 47.5	636 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 39.4	484 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 3217.3	784 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 431.8	798 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 337.8	1244 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 827.7	5447 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 74.9	1838 nanogramhour per milliliter (ngh/mL) Geometric Coefficient of Variation 179.3	—	—