Trial Outcomes & Findings for Bosutinib For Autosomal Dominant Polycystic Kidney Disease (NCT NCT01233869)

NCT ID: NCT01233869

Last Updated: 2016-03-11

Results Overview

TKV was measured by centrally evaluated Magnetic Resonance Imaging (MRI).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 172 participants
• Primary outcome timeframe: Baseline and Month 25 (end of Initial Treatment Period Visit [ITPV])
• Results posted on: 2016-03-11

Participant Flow

172 participants were enrolled in this study, of which 169 received at least 1 dose of study treatment.

Participant milestones

Measure	Bosutinib 200 mg/Day Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Initial Treatment Period (24 Months) STARTED	58	31	24	56
Initial Treatment Period (24 Months) COMPLETED	34	3	22	34
Initial Treatment Period (24 Months) NOT COMPLETED	24	28	2	22
Washout Period 30 Days STARTED	34	3	22	34
Washout Period 30 Days COMPLETED	34	3	22	34
Washout Period 30 Days NOT COMPLETED	0	0	0	0
Extended Treatment Period (46 Months) STARTED	34	3	22	34
Extended Treatment Period (46 Months) COMPLETED	20	0	17	18
Extended Treatment Period (46 Months) NOT COMPLETED	14	3	5	16

Reasons for withdrawal

Measure	Bosutinib 200 mg/Day Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Initial Treatment Period (24 Months) Death	1	0	0	0
Initial Treatment Period (24 Months) Adverse Event	9	17	0	3
Initial Treatment Period (24 Months) Not Related to Study Drug	14	11	2	19
Extended Treatment Period (46 Months) Lost to Follow-up	0	0	0	1
Extended Treatment Period (46 Months) Withdrawal by Subject	10	3	5	11
Extended Treatment Period (46 Months) Other	3	0	0	3
Extended Treatment Period (46 Months) Adverse Event	1	0	0	1

Baseline Characteristics

Bosutinib For Autosomal Dominant Polycystic Kidney Disease

Baseline characteristics by cohort

Measure	Bosutinib 200 mg/Day n=58 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=31 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=24 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo n=56 Participants Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.	Total n=169 Participants Total of all reporting groups
Age, Continuous	37.9 years STANDARD_DEVIATION 8.0 • n=93 Participants	41.3 years STANDARD_DEVIATION 4.9 • n=4 Participants	36.4 years STANDARD_DEVIATION 7.8 • n=27 Participants	38.5 years STANDARD_DEVIATION 7.4 • n=483 Participants	38.5 years STANDARD_DEVIATION 7.4 • n=36 Participants
Sex: Female, Male Female	28 Participants n=93 Participants	14 Participants n=4 Participants	15 Participants n=27 Participants	35 Participants n=483 Participants	92 Participants n=36 Participants
Sex: Female, Male Male	30 Participants n=93 Participants	17 Participants n=4 Participants	9 Participants n=27 Participants	21 Participants n=483 Participants	77 Participants n=36 Participants

PRIMARY outcome

Timeframe: Baseline and Month 25 (end of Initial Treatment Period Visit [ITPV])

Population: The modified intent-to-treat (mITT) population included all participants who were randomized and received at least 2-weeks' worth of treatment and have at least 1 follow-up MRI assessment that was preceded by a 1-month washout of the study drug; n=the number of participants analyzed at that time point in the respective arms.

TKV was measured by centrally evaluated Magnetic Resonance Imaging (MRI).

Outcome measures

Measure	Bosutinib 200 mg/Day n=27 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=6 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=21 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo n=33 Participants Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Change From Baseline (CFB) in Total Kidney Volume (TKV) at Month 25 Baseline (n=27,6,21,33)	1686.38 centimeter cube (cm^3) Standard Deviation 944.30	1418.96 centimeter cube (cm^3) Standard Deviation 629.34	1487.48 centimeter cube (cm^3) Standard Deviation 531.96	1670.33 centimeter cube (cm^3) Standard Deviation 640.69
Change From Baseline (CFB) in Total Kidney Volume (TKV) at Month 25 CFB at Month 25 (n=23,3,20,30)	85.05 centimeter cube (cm^3) Standard Deviation 231.09	102.45 centimeter cube (cm^3) Standard Deviation 257.30	-6.18 centimeter cube (cm^3) Standard Deviation 119.79	175.36 centimeter cube (cm^3) Standard Deviation 191.43

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24, Month 25 (end of ITPV), and early termination

Population: The mITT population included all participants who were randomized and received at least 2 weeks' worth of treatment and have at least 1 post-randomization follow-up MRI assessment; n=the number of participants analyzed at that time point in the respective arms.

eGFR was centrally evaluated. Glomerular filtration rate (GFR) is an index of kidney function that describes the flow of filtered fluid through the kidney. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to calculate eGFR. Month 25 is the end of the ITPV.

Outcome measures

Measure	Bosutinib 200 mg/Day n=58 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=31 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=24 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo n=56 Participants Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Months 12, 24, 25 and Early Termination CFB at Month 12 (n=26,4,21,31)	-6.38 mL/min/1.73m^2 Standard Deviation 11.60	-7.56 mL/min/1.73m^2 Standard Deviation 11.27	-11.52 mL/min/1.73m^2 Standard Deviation 10.86	1.30 mL/min/1.73m^2 Standard Deviation 9.71
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Months 12, 24, 25 and Early Termination CFB at Month 24 (n=23,3,20,30)	-8.47 mL/min/1.73m^2 Standard Deviation 15.02	-21.59 mL/min/1.73m^2 Standard Deviation 13.74	-13.16 mL/min/1.73m^2 Standard Deviation 13.41	-7.95 mL/min/1.73m^2 Standard Deviation 12.91
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Months 12, 24, 25 and Early Termination CFB at End of ITPV (n=23,3,20,30)	-5.00 mL/min/1.73m^2 Standard Deviation 10.78	-13.24 mL/min/1.73m^2 Standard Deviation 12.45	-9.92 mL/min/1.73m^2 Standard Deviation 14.55	-2.74 mL/min/1.73m^2 Standard Deviation 18.01
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Months 12, 24, 25 and Early Termination CFB at Early Termination (n=6,3,1,4)	-11.91 mL/min/1.73m^2 Standard Deviation 8.79	0.78 mL/min/1.73m^2 Standard Deviation 4.83	-10.24 mL/min/1.73m^2 Standard Deviation NA Standard deviation (SD) was not calculated as only 1 participant was analyzed.	-2.75 mL/min/1.73m^2 Standard Deviation 21.35

SECONDARY outcome

Timeframe: Baseline up to Month 25 (end of ITPV)

Population: The mITT-2 population included all participants who were randomized and received at least 2 weeks' worth of treatment and have at least 1 post-randomization follow-up MRI assessment (elimination of 1-month washout requirement).

The time to first occurrence or worsening of hypertension was observed (defined as the need for increased dose of or need for additional anti-hypertensive medication). The numbers presented correspond to the very first occurrence or worsening of hypertension in that treatment group.

Outcome measures

Measure	Bosutinib 200 mg/Day n=58 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=31 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=24 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo n=56 Participants Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Time to First Occurrence or Worsening of Hypertension	15 days	180 days	90 days	30 days

SECONDARY outcome

Timeframe: Baseline up to Month 25 (end of ITPV)

Population: The mITT-2 population included all participants who were randomized and received at least 2 weeks' worth of treatment and have at least 1 post-randomization follow-up MRI assessment (elimination of 1-month washout requirement).

The time to first occurrence or worsening of back and/or flank pain was observed (defined as initial onset of polycystic kidney disease [PKD]-related chronic back and/or flank pain; initiation of pain medication treatment for PKD-related chronic back and/or flank pain; addition of a pain medicine for treatment of PKD-related chronic back and/or flank pain; increase in dose of pain medication for treatment of PKD-related chronic back and/or flank pain). The numbers presented correspond to the very first occurrence or worsening of back and/or flank pain in that treatment group.

Outcome measures

Measure	Bosutinib 200 mg/Day n=58 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=31 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=24 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo n=56 Participants Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Time to First Occurrence or Worsening of Back and/or Flank Pain	30 days	30 days	270 days	15 days

SECONDARY outcome

Timeframe: Baseline up to Month 25 (end of ITPV)

Population: The mITT-2 population included all participants who were randomized and received at least 2 weeks' worth of treatment and have at least 1 post-randomization follow-up MRI assessment (elimination of 1-month washout requirement).

Gross hematuria is the presence of blood in the urine (defined as pink, red, or cola-colored urine due to the presence of red blood cells). The numbers presented correspond to the very first occurrence of gross hematuria in that treatment group.

Outcome measures

Measure	Bosutinib 200 mg/Day n=58 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=31 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=24 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo n=56 Participants Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Time to First Occurrence of Gross Hematuria	330 days	180 days	180 days	45 days

SECONDARY outcome

Timeframe: Baseline up to Month 25 (end of ITPV)

Population: The mITT-2 population included all participants who were randomized and received at least 2 weeks' worth of treatment and have at least 1 post-randomization follow-up MRI assessment (elimination of 1-month washout requirement).

Proteinuria is the presence of an excess of serum proteins in the urine, which may be an early sign of kidney disease. The numbers presented correspond to the very first occurrence of proteinuria in that treatment group.

Outcome measures

Measure	Bosutinib 200 mg/Day n=58 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=31 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=24 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo n=56 Participants Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Time to First Occurrence of Proteinuria	360 days	NA days No proteinuria events were observed.	270 days	540 days

SECONDARY outcome

Timeframe: Baseline up to Month 25 (end of ITPV)

Population: The mITT-2 population included all participants who were randomized and received at least 2 weeks' worth of treatment and have at least 1 post-randomization follow-up MRI assessment (elimination of 1-month washout requirement).

ESRD is when the kidneys permanently fail to work at a level needed for daily life. No participants developed ESRD during the treatment period, therefore the analysis of the onset of ESRD requiring ≥56 days of dialysis was not performed.

Outcome measures

Measure	Bosutinib 200 mg/Day n=58 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=31 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=24 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo n=56 Participants Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Time to First Occurrence of End-Stage Renal Disease (ESRD) Requiring Dialysis >=56 Days	NA days No participants developed ESRD during the treatment period, therefore the analysis of the onset of ESRD requiring ≥56 days of dialysis was not performed.	NA days No participants developed ESRD during the treatment period, therefore the analysis of the onset of ESRD requiring ≥56 days of dialysis was not performed.	NA days No participants developed ESRD during the treatment period, therefore the analysis of the onset of ESRD requiring ≥56 days of dialysis was not performed.	NA days No participants developed ESRD during the treatment period, therefore the analysis of the onset of ESRD requiring ≥56 days of dialysis was not performed.

SECONDARY outcome

Timeframe: Day 15, Months 6, 12, 18, 24, and 25 (end of ITPV)

Population: The safety analysis population included all participants who received at least 1 dose of study drug.

A BUN test can reveal how well the kidneys are working by measuring the amount of urea nitrogen in the blood. A high BUN level (>1.3 times the upper limit of normal) may suggest that the kidneys are not working properly. Month 25 is the end of the ITPV.

Outcome measures

Measure	Bosutinib 200 mg/Day n=58 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=31 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=24 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo n=56 Participants Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Number of Participants With High Blood Urea Nitrogen (BUN) Levels Day 15	0 participants	0 participants	2 participants	0 participants
Number of Participants With High Blood Urea Nitrogen (BUN) Levels Month 6	0 participants	0 participants	0 participants	0 participants
Number of Participants With High Blood Urea Nitrogen (BUN) Levels Month 12	0 participants	0 participants	0 participants	0 participants
Number of Participants With High Blood Urea Nitrogen (BUN) Levels Month 18	0 participants	0 participants	0 participants	0 participants
Number of Participants With High Blood Urea Nitrogen (BUN) Levels Month 24	0 participants	0 participants	1 participants	0 participants
Number of Participants With High Blood Urea Nitrogen (BUN) Levels End of ITPV	0 participants	0 participants	2 participants	0 participants

SECONDARY outcome

Timeframe: Day 15, Months 6, 12, 18, 24, and 25 (end of ITPV)

Population: The safety analysis population included all participants who received at least 1 dose of study drug.

A SCr test can reveal how well the kidneys are working by measuring the amount of urea nitrogen in the blood. A high SCr level (>1.3 times the upper limit of normal) may suggest that the kidneys are not working properly. Month 25 is the end of the ITPV.

Outcome measures

Measure	Bosutinib 200 mg/Day n=58 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=31 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=24 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo n=56 Participants Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Number of Participants With High Serum Creatinine (SCr) Levels Day 15	0 participants	1 participants	0 participants	0 participants
Number of Participants With High Serum Creatinine (SCr) Levels Month 6	0 participants	0 participants	0 participants	0 participants
Number of Participants With High Serum Creatinine (SCr) Levels Month 12	0 participants	0 participants	0 participants	1 participants
Number of Participants With High Serum Creatinine (SCr) Levels Month 18	0 participants	0 participants	0 participants	0 participants
Number of Participants With High Serum Creatinine (SCr) Levels Month 24	0 participants	1 participants	1 participants	1 participants
Number of Participants With High Serum Creatinine (SCr) Levels End of ITPV	0 participants	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: Day 1 (pre-dose and 1, 3, 5 and 24 hours post-dose), Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)

Population: The pharmacokinetic (PK) parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest; n=the number of participants analyzed at that time point in the respective arms.

Outcome measures

Measure	Bosutinib 200 mg/Day n=58 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=31 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=24 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Maximum Observed Plasma Concentration (Cmax) of Bosutinib Day 1 (n=58,31,24)	32.61 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 53	74.87 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 47	84.57 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 56	—
Maximum Observed Plasma Concentration (Cmax) of Bosutinib Day 15 (n=58,16,22)	68.72 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 43	127.90 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 28	155.00 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 31	—

SECONDARY outcome

Timeframe: Day 1 (pre-dose and 1, 3, 5 and 24 hours post-dose), Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)

Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest; n=the number of participants analyzed at that time point in the respective arms.

Outcome measures

Measure	Bosutinib 200 mg/Day n=58 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=31 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=24 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Bosutinib Day 1 (n=58,31,24)	3.00 hours Interval 1.0 to 24.0	3.00 hours Interval 2.8 to 23.8	4.86 hours Interval 1.0 to 5.25	—
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Bosutinib Day 15 (n=58,16,22)	3.95 hours Interval 0.0 to 25.6	3.00 hours Interval 1.0 to 8.0	5.00 hours Interval 1.0 to 8.12	—

SECONDARY outcome

Timeframe: Day 1 (pre-dose and 1, 3, 5 and 24 hours post-dose), Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)

Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest; n=the number of participants analyzed at that time point in the respective arms.

Area under the concentration-time profile from time 0 to time tau, the dosing interval, where tau=24 hours.

Outcome measures

Measure	Bosutinib 200 mg/Day n=58 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=31 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=24 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Area Under the Concentration-Time Profile From Time 0 to the Dosing Interval (AUCtau) of Bosutinib Day 1 (n=58,30,24)	437 ng*hr/mL Geometric Coefficient of Variation 48	1040 ng*hr/mL Geometric Coefficient of Variation 49	1149 ng*hr/mL Geometric Coefficient of Variation 50	—
Area Under the Concentration-Time Profile From Time 0 to the Dosing Interval (AUCtau) of Bosutinib Day 15 (n=58,16,22)	1059 ng*hr/mL Geometric Coefficient of Variation 45	2052 ng*hr/mL Geometric Coefficient of Variation 36	2384 ng*hr/mL Geometric Coefficient of Variation 34	—

SECONDARY outcome

Timeframe: Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)

Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.

Outcome measures

Measure	Bosutinib 200 mg/Day n=58 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=16 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=22 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Lowest Concentration Observed During the Dosing Interval (Cmin) of Bosutinib	25.15 ng/mL Geometric Coefficient of Variation 49	19.60 ng/mL Geometric Coefficient of Variation 20880	50.67 ng/mL Geometric Coefficient of Variation 50	—

SECONDARY outcome

Timeframe: Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)

Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

Outcome measures

Measure	Bosutinib 200 mg/Day n=58 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=16 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=22 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Apparent Oral Clearance (CL/F) of Bosutinib	188.8 L/hr Geometric Coefficient of Variation 45	195.0 L/hr Geometric Coefficient of Variation 36	167.8 L/hr Geometric Coefficient of Variation 34	—

SECONDARY outcome

Timeframe: Day 1 (pre-dose and 1, 3, 5 and 24 hours post-dose), Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)

Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest. There was no sufficient data to well-characterize the terminal phase, therefore Vz/F was not reported.

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 (pre-dose and 1, 3, 5 and 24 hours post-dose), Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)

Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest. There was no sufficient data to well-characterize the terminal phase, therefore t1/2 was not reported.

t1/2 is the time measured for the plasma concentration to decrease by one half.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)

Population: The PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.

Observed accumulation ratio (Rac) was calculated as AUC from time 0 to 24 hours (Day 15) divided by AUC from time 0 to 24 hours (Day 1).

Outcome measures

Measure	Bosutinib 200 mg/Day n=58 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=16 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=22 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Observed Accumulation Ratio (Rac) of Bosutinib	2.452 ratio Geometric Coefficient of Variation 36	2.280 ratio Geometric Coefficient of Variation 42	2.075 ratio Geometric Coefficient of Variation 41	—

SECONDARY outcome

Timeframe: Baseline and end of ITPV (Month 25)

Population: The mITT-2 population included all participants who were randomized and received at least 2 weeks' worth of treatment and have at least 1 post-randomization follow-up MRI assessment (elimination of 1-month washout); n=the number of participants analyzed in the respective arms.

The KDQoL-36 is a 36-item questionnaire on kidney disease-specific measure of patient-reported quality of life with 5 subscales: physical and mental functioning (items 1-12); burden of kidney disease subscale (items 13-16); symptoms and problems (items 17-28); effects of kidney disease on daily life subscale (items 29-36). The raw scores are transformed linearly to a range of 0 to 100, with higher scores indicating better quality of life.

Outcome measures

Measure	Bosutinib 200 mg/Day n=42 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=9 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=24 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo n=43 Participants Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Change From Baseline in Kidney Disease Quality of Life (KDQoL)-36 Scale Scores at Month 25 Burden of Disease: Baseline (n=42,9,24,43)	84.23 units on a scale Standard Deviation 18.48	84.722 units on a scale Standard Deviation 20.99	79.43 units on a scale Standard Deviation 24.97	74.86 units on a scale Standard Deviation 30.21
Change From Baseline in Kidney Disease Quality of Life (KDQoL)-36 Scale Scores at Month 25 Burden of Disease: CFB Month 25 (n=32,3,22,34)	-2.54 units on a scale Standard Deviation 15.70	-2.08 units on a scale Standard Deviation 9.55	0.57 units on a scale Standard Deviation 15.90	1.84 units on a scale Standard Deviation 19.13
Change From Baseline in Kidney Disease Quality of Life (KDQoL)-36 Scale Scores at Month 25 Kidney Disease Effects: Baseline (n=42,9,24,43)	93.30 units on a scale Standard Deviation 8.58	92.01 units on a scale Standard Deviation 11.06	91.54 units on a scale Standard Deviation 11.53	90.41 units on a scale Standard Deviation 14.10
Change From Baseline in Kidney Disease Quality of Life (KDQoL)-36 Scale Scores at Month 25 Kidney Disease Effects: CFB Month 25; n=32,3,22,34	1.07 units on a scale Standard Deviation 5.48	3.13 units on a scale Standard Deviation 5.41	-0.57 units on a scale Standard Deviation 9.72	3.22 units on a scale Standard Deviation 9.50
Change From Baseline in Kidney Disease Quality of Life (KDQoL)-36 Scale Scores at Month 25 SF-12 Mental Health: Baseline (n=42,9,24,43)	54.31 units on a scale Standard Deviation 6.39	51.11 units on a scale Standard Deviation 12.87	50.19 units on a scale Standard Deviation 9.28	51.33 units on a scale Standard Deviation 8.58
Change From Baseline in Kidney Disease Quality of Life (KDQoL)-36 Scale Scores at Month 25 SF-12 Mental Health: CFB Month 25 (n=32,3,22,34)	-1.50 units on a scale Standard Deviation 5.87	6.55 units on a scale Standard Deviation 6.30	1.34 units on a scale Standard Deviation 7.35	0.12 units on a scale Standard Deviation 10.25
Change From Baseline in Kidney Disease Quality of Life (KDQoL)-36 Scale Scores at Month 25 SF-12 Physical Health: Baseline (n=42,9,24,43)	50.52 units on a scale Standard Deviation 6.93	51.78 units on a scale Standard Deviation 6.40	49.64 units on a scale Standard Deviation 8.35	47.17 units on a scale Standard Deviation 10.93
Change From Baseline in Kidney Disease Quality of Life (KDQoL)-36 Scale Scores at Month 25 SF-12 Physical Health: CFB Month 25 (n=32,3,22,34)	-0.28 units on a scale Standard Deviation 5.81	-7.59 units on a scale Standard Deviation 7.63	-2.33 units on a scale Standard Deviation 8.16	2.32 units on a scale Standard Deviation 8.34
Change From Baseline in Kidney Disease Quality of Life (KDQoL)-36 Scale Scores at Month 25 Symptoms/Problems: Baseline (n=42,9,24,43)	93.13 units on a scale Standard Deviation 6.96	93.69 units on a scale Standard Deviation 7.35	90.72 units on a scale Standard Deviation 9.31	90.86 units on a scale Standard Deviation 9.29
Change From Baseline in Kidney Disease Quality of Life (KDQoL)-36 Scale Scores at Month 25 Symptoms/Problems: CFB Month 25 (n=32,3,22,34)	-2.42 units on a scale Standard Deviation 7.21	-8.33 units on a scale Standard Deviation 9.19	-3.75 units on a scale Standard Deviation 8.04	0.27 units on a scale Standard Deviation 9.31

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 30 days after last study drug administration

Population: The safety analysis population included all participants who received at least 1 dose of study drug.

An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.

Outcome measures

Measure	Bosutinib 200 mg/Day n=58 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=31 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=24 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo n=56 Participants Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	56 participants	30 participants	23 participants	51 participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	12 participants	4 participants	6 participants	5 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 30 days after last study drug administration

Population: The safety analysis population included all participants who received at least 1 dose of study drug.

The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell [RBC] count, RBC morphology, platelet count, white blood cell [WBC] count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen [BUN], creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, alkaline phosphatase, uric acid, albumin, and total protein; urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, microscopy [if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase]); others (coagulation panel, circulating immune complex, and complement activation).

Outcome measures

Measure	Bosutinib 200 mg/Day n=58 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=31 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=24 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo n=56 Participants Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern	53 participants	20 participants	23 participants	43 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 30 days after last study drug administration

Population: The safety analysis population included all participants who received at least 1 dose of study drug; n=the number of participants analyzed in the respective arms.

Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine/sitting pulse rate <40 or >120 beats per minute (bpm), standing pulse rate <40 or >140 bpm; systolic blood pressure (SBP) of >=30 millimeters of mercury (mm Hg) change from baseline in same posture or SBP <90 mm Hg, diastolic blood pressure (DBP) >=20 mmHg change from baseline in same posture or DBP <50 mm Hg.

Outcome measures

Measure	Bosutinib 200 mg/Day n=58 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=31 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=24 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo n=56 Participants Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Number of Participants With Potentially Clinically Significant Vital Signs Findings Supine SBP <90 mm Hg (n=2,2,1,4)	0 participants	0 participants	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Sitting SBP <90 mm Hg (n=58,29,24,54)	0 participants	0 participants	1 participants	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Supine DBP <50 mm Hg (n=2,2,1,4)	0 participants	0 participants	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Sitting DBP <50 mm Hg (n=58,29,24,54)	0 participants	1 participants	1 participants	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Supine Pulse Rate <40 or >120 bpm(n=2,2,1,4)	0 participants	0 participants	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Sitting Pulse Rate <40 or >120 bpm (n=58,29,24,54)	1 participants	0 participants	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Supine SBP ≥30 mm Hg Decrease (n=2,2,1,4)	0 participants	0 participants	1 participants	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Sitting SBP ≥30 mm Hg Decrease (n=58,29,24,54)	2 participants	1 participants	2 participants	2 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Supine DBP ≥20 mm Hg Decrease (n=2,2,1,4)	0 participants	0 participants	1 participants	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Sitting DBP ≥20 mm Hg Decrease (n=58,29,24,54)	12 participants	3 participants	3 participants	5 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Supine SBP ≥30 mm Hg Increase (n=2,2,1,4)	0 participants	0 participants	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Sitting SBP ≥30 mm Hg Increase (n=58,29,24,54)	3 participants	1 participants	3 participants	3 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Supine DBP ≥20 mm Hg Increase (n=2,2,1,4)	0 participants	0 participants	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Vital Signs Findings Sitting DBP ≥20 mm Hg Increase (n=58,29,24,54)	5 participants	3 participants	5 participants	5 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 30 days after last study drug administration

Population: The safety analysis population included all participants who received at least 1 dose of study drug; n=the number of participants analyzed in the respective arms.

ECGs were centrally evaluated. ECG parameters included PR interval, QRS interval, and corrected QT interval using Fridericia's formula (QTcF). Criteria for ECG changes meeting potential clinical concern included: PR interval greater than or equal to (≥)300 milliseconds (msec) or ≥25% increase when baseline is greater than (>)200 msec and ≥50% increase when baseline is less than or equal to (≤)200 msec; QRS interval ≥200 msec or ≥25%/50% increase from baseline; and QTcF ≥450 msec or ≥30 msec increase.

Outcome measures

Measure	Bosutinib 200 mg/Day n=58 Participants Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=31 Participants Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=24 Participants Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo n=56 Participants Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings PR Interval ≥300 msec (n=58,31,24,56)	0 participants	0 participants	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings QRS Complex ≥200 msec (n=58,31,24,56)	0 participants	0 participants	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings QTcF Interval 450-<480 msec (n=58,31,24,56)	3 participants	2 participants	0 participants	6 participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings QTcF Interval 480-<500 msec (n=58,31,24,56)	0 participants	0 participants	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings QTcF Interval ≥500 msec (n=58,31,24,56)	0 participants	0 participants	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings PR Interval ≥25/50% Increase (n=57,28,23,52)	0 participants	0 participants	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings QRS Complex ≥25/50% Increase (n=57,28,23,52)	0 participants	0 participants	0 participants	0 participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings QTcF Interval 30-<60 msec Increase (n=57,28,23,52)	4 participants	1 participants	1 participants	5 participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings QTcF Interval ≥60 msec Increase (n=57,28,23,52)	0 participants	0 participants	0 participants	0 participants

Adverse Events

Bosutinib 200 mg/Day

Serious events: 12 serious events

Other events: 56 other events

Deaths: 0 deaths

Bosutinib 400 mg/Day

Serious events: 4 serious events

Other events: 30 other events

Deaths: 0 deaths

Bosutinib 400/200 mg/Day

Serious events: 6 serious events

Other events: 23 other events

Deaths: 0 deaths

Placebo

Serious events: 5 serious events

Other events: 50 other events

Deaths: 0 deaths

Serious adverse events

Measure	Bosutinib 200 mg/Day n=58 participants at risk Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=31 participants at risk Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=24 participants at risk Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo n=56 participants at risk Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Blood and lymphatic system disorders Anaemia	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.2% 1/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Cardiac disorders Ventricular extrasystoles	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Abdominal pain	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Peptic ulcer	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Subileus	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Hepatobiliary disorders Hepatitis acute	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Appendicitis	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Gastroenteritis	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Hepatitis C	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.8% 1/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Pneumonia	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Pyelonephritis acute	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.2% 1/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Renal cyst infection	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.8% 1/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Sepsis	3.4% 2/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.2% 1/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Urinary tract infection	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Alanine aminotransferase increased	3.4% 2/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Amylase increased	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Aspartate aminotransferase increased	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Lipase increased	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.8% 1/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Sacroiliitis	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Spondylitis	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Nervous system disorders Intracranial aneurysm	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.2% 1/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Nervous system disorders Syncope	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Psychiatric disorders Insomnia	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Psychiatric disorders Psychosomatic disease	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Renal and urinary disorders Calculus ureteric	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.2% 1/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Renal and urinary disorders Haematuria	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.8% 1/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Renal and urinary disorders Renal cyst haemorrhage	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.2% 1/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Renal and urinary disorders Renal cyst ruptured	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.8% 1/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Renal and urinary disorders Renal failure acute	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Renal and urinary disorders Renal haemorrhage	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Reproductive system and breast disorders Cervix disorder	0.00% 0/28 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/14 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.7% 1/15 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/35 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.

Other adverse events

Measure	Bosutinib 200 mg/Day n=58 participants at risk Participants received bosutinib 200 mg tablet orally once daily (QD) in the morning with food for 24 months in the Initial Treatment Period (ITP). After a 30-day washout period, participants who entered the Extended Treatment Period (ETP) continued to receive bosutinib 200 mg orally QD for up to 46 months.	Bosutinib 400 mg/Day n=31 participants at risk Participants received bosutinib 400 mg tablet orally QD in the morning with food for 24 months in the ITP. All participants were dose-reduced during the ITP based on a protocol amendment. Those who remained active in the study at the time of the amendment are represented in the bosutinib 400/200 mg/day group.	Bosutinib 400/200 mg/Day n=24 participants at risk Participants received bosutinib 400 mg and were dose-reduced to 200 mg tablet (based on protocol amendment) orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive bosutinib 200 mg orally QD for up to 46 months.	Placebo n=56 participants at risk Participants received placebo tablet orally QD in the morning with food for 24 months in the ITP. After a 30-day washout period, participants who entered the ETP continued to receive placebo matched bosutinib QD for up to 46 months.
Blood and lymphatic system disorders Anaemia	12.1% 7/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	12.9% 4/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	20.8% 5/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.6% 2/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Blood and lymphatic system disorders Eosinophilia	5.2% 3/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.2% 1/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Cardiac disorders Pericardial effusion	3.4% 2/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.3% 2/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Abdominal distension	5.2% 3/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.5% 2/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.3% 2/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.4% 3/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Abdominal pain	6.9% 4/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	25.8% 8/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.3% 2/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	12.5% 7/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Abdominal pain upper	8.6% 5/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	22.6% 7/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	33.3% 8/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.9% 5/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Constipation	3.4% 2/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.5% 2/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.2% 1/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.8% 1/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Diarrhoea	44.8% 26/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	83.9% 26/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	75.0% 18/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	19.6% 11/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Dyspepsia	10.3% 6/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.5% 2/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	12.5% 3/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.4% 3/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.4% 3/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Nausea	36.2% 21/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	48.4% 15/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	54.2% 13/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	16.1% 9/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Vomiting	10.3% 6/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	35.5% 11/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	37.5% 9/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	7.1% 4/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
General disorders Asthenia	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	12.5% 3/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.8% 1/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
General disorders Chest pain	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.5% 2/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
General disorders Fatigue	6.9% 4/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	25.8% 8/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.3% 2/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	10.7% 6/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
General disorders Influenza-like illness	3.4% 2/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	12.5% 3/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	10.7% 6/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
General disorders Oedema peripheral	3.4% 2/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.2% 1/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.4% 3/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
General disorders Pain	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.4% 3/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
General disorders Pyrexia	3.4% 2/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	9.7% 3/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.3% 2/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.8% 1/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Hepatobiliary disorders Hepatocellular injury	5.2% 3/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Immune system disorders Hypersensitivity	3.4% 2/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.4% 3/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Bronchitis	5.2% 3/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.5% 2/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.3% 2/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.4% 3/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Cystitis	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	12.5% 3/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.8% 1/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Gastroenteritis viral	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.2% 1/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.4% 3/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Influenza	3.4% 2/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.2% 1/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.4% 3/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Nasopharyngitis	20.7% 12/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	9.7% 3/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	33.3% 8/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	14.3% 8/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Pharyngitis	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	12.5% 3/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	7.1% 4/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Rhinitis	3.4% 2/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.3% 2/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.6% 2/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Sinusitis	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.4% 3/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Upper respiratory tract infection	10.3% 6/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	12.9% 4/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	29.2% 7/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	12.5% 7/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Urinary tract infection	13.8% 8/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.5% 2/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.3% 2/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	14.3% 8/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Vaginal infection	3.6% 1/28 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/14 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/15 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.6% 3/35 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Viral infection	3.4% 2/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.2% 1/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.4% 3/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Infections and infestations Vulvovaginal mycotic infection	3.6% 1/28 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/14 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.7% 1/15 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.9% 1/35 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Injury, poisoning and procedural complications Excoriation	5.2% 3/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.2% 1/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Alanine aminotransferase increased	31.0% 18/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	51.6% 16/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	50.0% 12/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	7.1% 4/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Amylase increased	3.4% 2/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	12.9% 4/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	12.5% 3/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.8% 1/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Aspartate aminotransferase increased	29.3% 17/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	35.5% 11/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	25.0% 6/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.4% 3/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Blood creatine phosphokinase increased	19.0% 11/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	9.7% 3/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	25.0% 6/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.9% 5/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Blood creatinine increased	3.4% 2/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.3% 2/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.6% 2/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Blood lactate dehydrogenase increased	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.5% 2/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Blood phosphorus decreased	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.5% 2/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Gamma-glutamyltransferase increased	6.9% 4/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Haemoglobin decreased	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.3% 2/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Lipase increased	8.6% 5/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	19.4% 6/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	25.0% 6/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.4% 3/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Investigations Weight increased	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.5% 2/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	12.5% 3/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Metabolism and nutrition disorders Decreased appetite	3.4% 2/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	12.9% 4/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	16.7% 4/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Metabolism and nutrition disorders Hypophosphataemia	3.4% 2/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.3% 2/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.8% 1/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Arthralgia	8.6% 5/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.2% 1/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.9% 5/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Back pain	15.5% 9/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.5% 2/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.2% 1/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	14.3% 8/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Flank pain	17.2% 10/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	16.1% 5/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.9% 5/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Muscle spasms	5.2% 3/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.4% 3/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.2% 3/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.3% 2/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.6% 2/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.4% 3/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Pain in extremity	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.4% 3/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/28 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/14 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.7% 1/15 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/35 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Nervous system disorders Dizziness	12.1% 7/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.5% 2/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	16.7% 4/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.4% 3/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Nervous system disorders Dysgeusia	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.5% 2/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Nervous system disorders Headache	15.5% 9/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	9.7% 3/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.3% 2/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	21.4% 12/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Psychiatric disorders Insomnia	5.2% 3/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.8% 1/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Renal and urinary disorders Haematuria	6.9% 4/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	9.7% 3/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.2% 1/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	7.1% 4/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Renal and urinary disorders Proteinuria	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.3% 2/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.4% 3/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Renal and urinary disorders Renal failure acute	3.4% 2/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.3% 2/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Reproductive system and breast disorders Amenorrhoea	0.00% 0/28 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/14 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.7% 1/15 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/35 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Reproductive system and breast disorders Cervical dysplasia	0.00% 0/28 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/14 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.7% 1/15 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/35 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Reproductive system and breast disorders Menorrhagia	3.6% 1/28 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/14 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.7% 1/15 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.9% 1/35 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Reproductive system and breast disorders Metrorrhagia	3.6% 1/28 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/14 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.7% 1/15 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/35 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Reproductive system and breast disorders Ovarian cyst	0.00% 0/28 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	7.1% 1/14 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/15 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.9% 1/35 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Reproductive system and breast disorders Vaginal inflammation	0.00% 0/28 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/14 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.7% 1/15 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	2.9% 1/35 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Cough	3.4% 2/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	9.7% 3/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	12.5% 3/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	7.1% 4/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.6% 5/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.5% 2/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.2% 1/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.6% 2/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Acne	6.9% 4/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.8% 1/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Alopecia	3.4% 2/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	3.2% 1/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	12.5% 3/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	5.4% 3/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Dermatitis allergic	3.4% 2/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	8.3% 2/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Pruritis	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.5% 2/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	4.2% 1/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	1.8% 1/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	6.5% 2/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Vascular disorders Hypertension	13.8% 8/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	9.7% 3/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	20.8% 5/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	16.1% 9/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Vascular disorders Hypotension	1.7% 1/58 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/31 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	12.5% 3/24 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.	0.00% 0/56 • Baseline up to 30 days after last study drug administration The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.

Additional Information

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Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER