Trial Outcomes & Findings for Study of the Safety, Tolerability, and Pharmacokinetics of LHW090 in Patients With Moderately Impaired Renal Function (NCT NCT02678000)

NCT ID: NCT02678000

Last Updated: 2021-10-06

Results Overview

Any sign or symptom that occurs during the study treatment plus the 30 days post treatment. For LHW090, incidence of AEs by primary organ class presented

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 84 participants
• Primary outcome timeframe: Adverse events were collected from first dose of study treatment until end of study treatment, (12 days dosing period + 9 days follow up (PART 1) plus 30 days post treatment, up to maximum duration of approximately 20 months
• Results posted on: 2021-10-06

Participant Flow

All subjects (N=11) who enrolled in in PART 1 completed the study : LHW090 (N=7) and placebo (N=4). Of all subjects (N=73) in PART 2, a total of 69 subjects completed and 4 subjects discontinued.

All subjects (N=11) who enrolled in in PART 1 completed the study : LHW090 (N=7) and placebo (N=4). Of all subjects (N=73) in PART 2, a total of 69 subjects completed and 4 subjects discontinued.

Participant milestones

Measure	LHW090 (PART 1) For Part 1, patients will receive 3 doses of LHW090 once daily with escalating doses every 4 days for a total 12 days of treatment.	Placebo (PART 1) For Part 1, patients will receive matching placebo once daily for 12 days.	LHW090 100mg (PART 2) For PART 2, patients will receive LWH090 100 mg for 4 weeks	LHW090 200mg (PART 2) For PART 2, patients will receive LWH090 200 mg for 4 weeks	Placebo (PART 2) For Part 2, patients will receive matching placebo once daily for 4 weeks.
PART 1 STARTED	7	4	0	0	0
PART 1 COMPLETED	7	4	0	0	0
PART 1 NOT COMPLETED	0	0	0	0	0
PART 2 STARTED	0	0	28	27	18
PART 2 COMPLETED	0	0	25	26	18
PART 2 NOT COMPLETED	0	0	3	1	0

Reasons for withdrawal

Measure	LHW090 (PART 1) For Part 1, patients will receive 3 doses of LHW090 once daily with escalating doses every 4 days for a total 12 days of treatment.	Placebo (PART 1) For Part 1, patients will receive matching placebo once daily for 12 days.	LHW090 100mg (PART 2) For PART 2, patients will receive LWH090 100 mg for 4 weeks	LHW090 200mg (PART 2) For PART 2, patients will receive LWH090 200 mg for 4 weeks	Placebo (PART 2) For Part 2, patients will receive matching placebo once daily for 4 weeks.
PART 2 Adverse Event	0	0	2	1	0
PART 2 Withdrawal by Subject	0	0	1	0	0

Baseline Characteristics

Study of the Safety, Tolerability, and Pharmacokinetics of LHW090 in Patients With Moderately Impaired Renal Function

Baseline characteristics by cohort

Measure	LHW090 (PART 1) n=7 Participants For Part 1, patients will receive 3 doses of LHW090 once daily with escalating doses every 4 days for a total 12 days of treatment.	Placebo (PART 1) n=4 Participants For Part 1, patients will receive matching placebo once daily for 12 days.	LHW090 100mg (PART 2) n=28 Participants For PART 2, patients will receive LWH090 100 mg for 4 weeks	LHW090 200mg (PART 2) n=27 Participants For PART 2, patients will receive LWH090 200 mg for 4 weeks	Placebo (PART 2) n=18 Participants For Part 2, patients will receive matching placebo once daily for 4 weeks.	Total n=84 Participants Total of all reporting groups
Age, Continuous	68.3 years STANDARD_DEVIATION 3.64 • n=5 Participants	67.5 years STANDARD_DEVIATION 16.01 • n=7 Participants	71.0 years STANDARD_DEVIATION 9.18 • n=5 Participants	69.0 years STANDARD_DEVIATION 8.82 • n=4 Participants	65.3 years STANDARD_DEVIATION 11.58 • n=21 Participants	68.8 years STANDARD_DEVIATION 9.69 • n=10 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants	10 Participants n=4 Participants	9 Participants n=21 Participants	31 Participants n=10 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	1 Participants n=7 Participants	20 Participants n=5 Participants	17 Participants n=4 Participants	9 Participants n=21 Participants	53 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	0 Participants n=21 Participants	6 Participants n=10 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	3 Participants n=7 Participants	27 Participants n=5 Participants	24 Participants n=4 Participants	18 Participants n=21 Participants	78 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants

PRIMARY outcome

Timeframe: Adverse events were collected from first dose of study treatment until end of study treatment, (12 days dosing period + 9 days follow up (PART 1) plus 30 days post treatment, up to maximum duration of approximately 20 months

Population: Safety Analysis Set -All subjects that received study drug and with no protocol deviations with relevant impact on safety

Any sign or symptom that occurs during the study treatment plus the 30 days post treatment. For LHW090, incidence of AEs by primary organ class presented

Outcome measures

Measure	LHW090 25 mg (PART 1) n=7 Participants For Part 1, patients will receive 3 doses of LHW090 25 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	LHW090 50 mg (PART 1) n=7 Participants For Part 1, patients will receive 3 doses of LHW090 50 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	LHW090 100 mg (PART 1) n=7 Participants For Part 1, patients will receive 3 doses of LHW090 100 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	Placebo (PART 1) n=4 Participants For Part 1, patients will receive matching placebo once daily for 12 days.	LHW090/LHV527 50 mg (PART 1) For Part 1, patients will receive 3 doses of LHW090 50 mg once daily with escalating doses every 4 days for a total 12 days of treatment. (PK draw with active metabolite, LHV527)	LHW090/LHV527 100 mg (PART 1) For Part 1, patients will receive 3 doses of LHW090 100 mg once daily with escalating doses every 4 days for a total 12 days of treatment. (PK draw with active metabolite, LHV527)
Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) Number of patients with at least one AE	1 Count of Participants	0 Count of Participants	1 Count of Participants	2 Count of Participants	—	—
Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) Gastrointestinal disorders	1 Count of Participants	0 Count of Participants	1 Count of Participants	2 Count of Participants	—	—
Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) Skin and subcutaneous tissue disorders	0 Count of Participants	0 Count of Participants	1 Count of Participants	2 Count of Participants	—	—
Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) General disorders & administration site conditions	0 Count of Participants	0 Count of Participants	0 Count of Participants	1 Count of Participants	—	—
Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) Musculoskeletal and connective tissue disorders	0 Count of Participants	0 Count of Participants	0 Count of Participants	1 Count of Participants	—	—
Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) Nervous system disorders	0 Count of Participants	0 Count of Participants	0 Count of Participants	1 Count of Participants	—	—
Number of Patients With Reported Adverse Events Receiving Escalating Doses of LHW090 (Part 1) Psychiatric disorders	0 Count of Participants	0 Count of Participants	0 Count of Participants	1 Count of Participants	—	—

PRIMARY outcome

Timeframe: Within 60 minutes prior to dosing, post dose +/- 10 min from greater or equal to 1 hr to 24 hrs.

Population: PK Analysis Set -Subjects with at least one available valid PK concentration measurement, who received study drug and experienced no protocol deviations with relevant impact on PK data

The area under the plasma concentration-time curve from time zero to 24 hours. Area Under the Curve (AUC0-t) after 4 days dosing will be reported for PART 1. LHW090 and LHV527 (its active metabolite)

Outcome measures

Measure	LHW090 25 mg (PART 1) n=7 Participants For Part 1, patients will receive 3 doses of LHW090 25 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	LHW090 50 mg (PART 1) n=7 Participants For Part 1, patients will receive 3 doses of LHW090 50 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	LHW090 100 mg (PART 1) n=7 Participants For Part 1, patients will receive 3 doses of LHW090 100 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	Placebo (PART 1) n=7 Participants For Part 1, patients will receive matching placebo once daily for 12 days.	LHW090/LHV527 50 mg (PART 1) n=7 Participants For Part 1, patients will receive 3 doses of LHW090 50 mg once daily with escalating doses every 4 days for a total 12 days of treatment. (PK draw with active metabolite, LHV527)	LHW090/LHV527 100 mg (PART 1) n=7 Participants For Part 1, patients will receive 3 doses of LHW090 100 mg once daily with escalating doses every 4 days for a total 12 days of treatment. (PK draw with active metabolite, LHV527)
Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' Where t is a Defined Time Point After Administration (AUC0-t) (PART 1)	3750 h*ng/mL Standard Deviation 815	7150 h*ng/mL Standard Deviation 1480	13900 h*ng/mL Standard Deviation 2180	19200 h*ng/mL Standard Deviation 3990	36500 h*ng/mL Standard Deviation 5720	68800 h*ng/mL Standard Deviation 11800

PRIMARY outcome

Timeframe: Baseline, within 24 to 48 hours of post-dose weekly for up to 8 weeks

Population: Safety Analysis Set -All subjects that received study drug and with no protocol deviations with relevant impact on safety

Patients who developed a renal event will be reported (defined as a ≥0.3 mg/dL increase in serum creatinine from baseline within 24-48 hours post dose )

Outcome measures

Measure	LHW090 25 mg (PART 1) n=28 Participants For Part 1, patients will receive 3 doses of LHW090 25 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	LHW090 50 mg (PART 1) n=27 Participants For Part 1, patients will receive 3 doses of LHW090 50 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	LHW090 100 mg (PART 1) n=18 Participants For Part 1, patients will receive 3 doses of LHW090 100 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	Placebo (PART 1) For Part 1, patients will receive matching placebo once daily for 12 days.	LHW090/LHV527 50 mg (PART 1) For Part 1, patients will receive 3 doses of LHW090 50 mg once daily with escalating doses every 4 days for a total 12 days of treatment. (PK draw with active metabolite, LHV527)	LHW090/LHV527 100 mg (PART 1) For Part 1, patients will receive 3 doses of LHW090 100 mg once daily with escalating doses every 4 days for a total 12 days of treatment. (PK draw with active metabolite, LHV527)
Number of Patients Who Developed a Renal Event (PART 2)	0 Participants	1 Participants	0 Participants	—	—	—

SECONDARY outcome

Timeframe: PART 1: within 60 minutes prior to dosing, post dose +/- 10 min from greater or equal to 1 hr to 24 hrs. PART 2: within 60 min +/- 10 min from greater or equal to 1 hr to 8 hours after 4 weeks dosing.

Population: PK Analysis Set - Subjects with at least one available valid PK concentration measurement, who received study drug and experienced no protocol deviations with relevant impact on PK data

The observed maximum plasma (or serum or blood) concentration following drug administration for PART 1 and PART 2

Outcome measures

Measure	LHW090 25 mg (PART 1) n=7 Participants For Part 1, patients will receive 3 doses of LHW090 25 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	LHW090 50 mg (PART 1) n=7 Participants For Part 1, patients will receive 3 doses of LHW090 50 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	LHW090 100 mg (PART 1) n=7 Participants For Part 1, patients will receive 3 doses of LHW090 100 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	Placebo (PART 1) n=7 Participants For Part 1, patients will receive matching placebo once daily for 12 days.	LHW090/LHV527 50 mg (PART 1) n=7 Participants For Part 1, patients will receive 3 doses of LHW090 50 mg once daily with escalating doses every 4 days for a total 12 days of treatment. (PK draw with active metabolite, LHV527)	LHW090/LHV527 100 mg (PART 1) For Part 1, patients will receive 3 doses of LHW090 100 mg once daily with escalating doses every 4 days for a total 12 days of treatment. (PK draw with active metabolite, LHV527)
Cmax : Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Observed Maximum Plasma Concentration Following Administration of LHW090 (PART 1/PART 2) PK Value for LHW090/LHV527(active metabolite)	1690 ng / mL Standard Deviation 338	3070 ng / mL Standard Deviation 682	5100 ng / mL Standard Deviation 734	6200 ng / mL Standard Deviation 1560	10300 ng / mL Standard Deviation 1440	—
Cmax : Pharmacokinetics of LHW090/LHV527 (Active Metabolite) in Plasma: Observed Maximum Plasma Concentration Following Administration of LHW090 (PART 1/PART 2) PK Value for LHW090	1160 ng / mL Standard Deviation 589	2000 ng / mL Standard Deviation 1020	4230 ng / mL Standard Deviation 1400	4470 ng / mL Standard Deviation 1690	7530 ng / mL Standard Deviation 3750	—

SECONDARY outcome

Timeframe: PART 2: within 60 min +/- 10 min from greater or equal to 1 hr to 8 hours after 4 weeks dosing

Population: PK Analysis Set -Subjects with at least one available valid PK concentration measurement, who received study drug and experienced no protocol deviations with relevant impact on PK data

The area under the plasma concentration-time curve from time zero to 24 hours

Outcome measures

Measure	LHW090 25 mg (PART 1) n=28 Participants For Part 1, patients will receive 3 doses of LHW090 25 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	LHW090 50 mg (PART 1) n=27 Participants For Part 1, patients will receive 3 doses of LHW090 50 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	LHW090 100 mg (PART 1) n=28 Participants For Part 1, patients will receive 3 doses of LHW090 100 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	Placebo (PART 1) n=27 Participants For Part 1, patients will receive matching placebo once daily for 12 days.	LHW090/LHV527 50 mg (PART 1) For Part 1, patients will receive 3 doses of LHW090 50 mg once daily with escalating doses every 4 days for a total 12 days of treatment. (PK draw with active metabolite, LHV527)	LHW090/LHV527 100 mg (PART 1) For Part 1, patients will receive 3 doses of LHW090 100 mg once daily with escalating doses every 4 days for a total 12 days of treatment. (PK draw with active metabolite, LHV527)
AUC0-t: Pharmacokinetics of LHW090/LHV527 (Active Metabolite)in Plasma: Area Under the Plasma Concentration-time Curve From Time Zero Time 't' Where t is a Defined Time Point After Administration (PART 2)	21500 h* ng/mL Standard Deviation 6810	42900 h* ng/mL Standard Deviation 20700	96700 h* ng/mL Standard Deviation 32800	181000 h* ng/mL Standard Deviation 51100	—	—

SECONDARY outcome

Timeframe: Part 1: within 60 minutes prior to dosing, post dose +/- 10 min from greater or equal to 1 hr to 24 hrs. Part 2: within 60 min +/- 10 min from greater or equal to 1 hr to 8 hours after 4 weeks dosing

Population: PK Analysis Set-Subjects with at least one available valid PK concentration measurement, who received study drug and experienced no protocol deviations with relevant impact on PK data

The time to reach the maximum concentration after drug administration

Outcome measures

Measure	LHW090 25 mg (PART 1) n=7 Participants For Part 1, patients will receive 3 doses of LHW090 25 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	LHW090 50 mg (PART 1) n=7 Participants For Part 1, patients will receive 3 doses of LHW090 50 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	LHW090 100 mg (PART 1) n=7 Participants For Part 1, patients will receive 3 doses of LHW090 100 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	Placebo (PART 1) n=7 Participants For Part 1, patients will receive matching placebo once daily for 12 days.	LHW090/LHV527 50 mg (PART 1) n=7 Participants For Part 1, patients will receive 3 doses of LHW090 50 mg once daily with escalating doses every 4 days for a total 12 days of treatment. (PK draw with active metabolite, LHV527)	LHW090/LHV527 100 mg (PART 1) For Part 1, patients will receive 3 doses of LHW090 100 mg once daily with escalating doses every 4 days for a total 12 days of treatment. (PK draw with active metabolite, LHV527)
Tmax: Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (PART 1/PART 2) PK Value for LHW090/LHV527(active metabolite)	3.58 hour (hr) Interval 2.0 to 12.0	4.00 hour (hr) Interval 2.0 to 12.0	4.00 hour (hr) Interval 2.0 to 8.0	3.00 hour (hr) Interval 2.0 to 8.0	4.00 hour (hr) Interval 3.0 to 12.0	—
Tmax: Pharmacokinetics of LHW090/LHV527 in Plasma: Time to Reach the Maximum Concentration After Administration of LHW090 (PART 1/PART 2) PK Value for LHW090	2.00 hour (hr) Interval 1.0 to 3.0	1.02 hour (hr) Interval 1.0 to 3.0	1.00 hour (hr) Interval 1.0 to 4.0	2.00 hour (hr) Interval 1.0 to 4.0	2.50 hour (hr) Interval 1.0 to 12.0	—

Adverse Events

LHW090 25 mg (PART 1)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

LHW090 50 mg (PART 1)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

LHW090 100 mg (PART 1)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

PART 1 Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

LHW090 100mg (PART 2)

Serious events: 3 serious events

Other events: 13 other events

Deaths: 0 deaths

LHW090 200 mg (PART 2)

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Placebo (PART 2

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	LHW090 25 mg (PART 1) n=7 participants at risk For Part 1, patients will receive 3 doses of LHW090 25 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	LHW090 50 mg (PART 1) n=7 participants at risk For Part 1, patients will receive 3 doses of LHW090 50 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	LHW090 100 mg (PART 1) n=7 participants at risk For Part 1, patients will receive 3 doses of LHW090 100 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	PART 1 Placebo n=4 participants at risk For Part 1, patients will receive matching placebo once daily for 12 days.	LHW090 100mg (PART 2) n=28 participants at risk For PART 2, patients will receive LWH090 100 mg once daily for 4 weeks	LHW090 200 mg (PART 2) n=27 participants at risk For PART 2, patients will receive LWH090 200 mg once daily for 4 weeks	Placebo (PART 2 n=18 participants at risk For Part 2, patients will receive matching placebo once daily for 4 weeks.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.6% 1/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Injury, poisoning and procedural complications Skin laceration	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.6% 1/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.6% 1/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.

Other adverse events

Measure	LHW090 25 mg (PART 1) n=7 participants at risk For Part 1, patients will receive 3 doses of LHW090 25 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	LHW090 50 mg (PART 1) n=7 participants at risk For Part 1, patients will receive 3 doses of LHW090 50 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	LHW090 100 mg (PART 1) n=7 participants at risk For Part 1, patients will receive 3 doses of LHW090 100 mg once daily with escalating doses every 4 days for a total 12 days of treatment.	PART 1 Placebo n=4 participants at risk For Part 1, patients will receive matching placebo once daily for 12 days.	LHW090 100mg (PART 2) n=28 participants at risk For PART 2, patients will receive LWH090 100 mg once daily for 4 weeks	LHW090 200 mg (PART 2) n=27 participants at risk For PART 2, patients will receive LWH090 200 mg once daily for 4 weeks	Placebo (PART 2 n=18 participants at risk For Part 2, patients will receive matching placebo once daily for 4 weeks.
Nervous system disorders Headache	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	25.0% 1/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.6% 1/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Ear and labyrinth disorders Vertigo	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.6% 1/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Eye disorders Eye pruritus	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.6% 1/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Eye disorders Lacrimation increased	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.6% 1/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	5.6% 1/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Gastrointestinal disorders Diarrhoea	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	7.1% 2/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	14.8% 4/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	5.6% 1/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Gastrointestinal disorders Dry mouth	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	25.0% 1/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Gastrointestinal disorders Dyspepsia	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	5.6% 1/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Gastrointestinal disorders Faeces discoloured	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	25.0% 1/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Gastrointestinal disorders Frequent bowel movements	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Gastrointestinal disorders Nausea	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.6% 1/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
General disorders Chest discomfort	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
General disorders Fatigue	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	7.1% 2/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
General disorders Infusion site haemorrhage	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	25.0% 1/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
General disorders Oedema peripheral	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.6% 1/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	11.1% 2/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
General disorders Pyrexia	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	5.6% 1/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
General disorders Xerosis	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	5.6% 1/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Immune system disorders Hypersensitivity	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.6% 1/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Infections and infestations Gastrointestinal infection	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Infections and infestations Nasopharyngitis	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	5.6% 1/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Infections and infestations Rhinitis	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Infections and infestations Urinary tract infection	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Investigations Blood creatinine increased	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	5.6% 1/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Investigations Blood pressure decreased	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	7.4% 2/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Metabolism and nutrition disorders Gout	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.6% 1/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Metabolism and nutrition disorders Lactose intolerance	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	5.6% 1/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	5.6% 1/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	25.0% 1/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Nervous system disorders Dizziness	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.6% 1/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Psychiatric disorders Abnormal dreams	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	25.0% 1/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Psychiatric disorders Apathy	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.6% 1/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Psychiatric disorders Insomnia	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Psychiatric disorders Sleep disorder	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	7.4% 2/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Renal and urinary disorders Dysuria	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.6% 1/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Renal and urinary disorders Haematuria	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	5.6% 1/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Renal and urinary disorders Pollakiuria	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.6% 1/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	5.6% 1/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Respiratory, thoracic and mediastinal disorders Nasal dryness	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Respiratory, thoracic and mediastinal disorders Nasal pruritus	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	14.8% 4/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	5.6% 1/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Skin and subcutaneous tissue disorders Acne	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.6% 1/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	25.0% 1/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Skin and subcutaneous tissue disorders Drug eruption	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	25.0% 1/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	5.6% 1/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	21.4% 6/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	5.6% 1/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Skin and subcutaneous tissue disorders Pruritus generalised	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	7.4% 2/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.7% 1/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Vascular disorders Haematoma	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	3.6% 1/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	5.6% 1/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.
Vascular disorders Hypotension	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	7.1% 2/28 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	7.4% 2/27 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.	0.00% 0/18 • Adverse events were collected from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to maximum duration of approximately 20 months Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: Novartis.email@novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER