Trial Outcomes & Findings for A Phase II Study in Patients With Moderate to Severe Active Ulcerative Colitis. (NCT NCT03675477)

NCT ID: NCT03675477

Last Updated: 2023-06-02

Results Overview

Clinical response is defined as a decrease from baseline in a 9-point modified Mayo score of at least 2 points and at least 30%, with an accompanying reduction in the subscore for rectal bleeding of at least 1 point or absolute subscore for rectal bleeding of 0 or 1. The 9-point modified Mayo score is the Mayo score excluding the Physician Global Assessment sub-score, hence the maximum is 9 points and the minimum is 0 point, includes: Stool Frequency 0 = Normal 1. = 1-2 stools/day more than normal 2. = 3-4 stools/day more than normal 3. = 5 or more stools/day than normal Rectal bleeding 0 = None 1. = Visible blood with stool less than half the time 2. = Visible blood with stool half of the time or more 3. = Passing blood alone Mucosal appearance at endoscopy 0 = Normal or inactive disease 1. = Mild disease (erythema, decreased vascular pattern, mild friability 2. = Moderate disease (marked erythema, absent vascular pattern, friability, erosio

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 164 participants
• Primary outcome timeframe: Week 8
• Results posted on: 2023-06-02

Participant Flow

Participant milestones

Measure	SHR0302 8mg QD Participants randomized in this arm will receive SHR0302 8mg QD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 8mg QD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	SHR0302 4mg BD Participants randomized in this arm will receive SHR0302 4mg BD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 4mg BD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	SHR0302 4mg QD Participants randomized in this arm will receive SHR0302 4mg QD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 4mg QD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	Placebo Participants randomized in this arm will receive the placebo until week 8, and then will be re-randomized into one of the 3 active arms ( 4mg QD, 4mg BD, 8mg QD of SHR0302) in a 1:1:1 allocation ratio until the end of the study at week 16. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor). Placebos: Placebo Oral Tablet
Treatment Phase STARTED	41	41	41	41
Treatment Phase COMPLETED	41	41	41	41
Treatment Phase NOT COMPLETED	0	0	0	0
Extension Phase STARTED	47	49	48	0
Extension Phase COMPLETED	47	49	48	0
Extension Phase NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase II Study in Patients With Moderate to Severe Active Ulcerative Colitis.

Baseline characteristics by cohort

Measure	SHR0302 8mg QD n=41 Participants Participants randomized in this arm will receive SHR0302 8mg QD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 8mg QD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	SHR0302 4mg BD n=41 Participants Participants randomized in this arm will receive SHR0302 4mg BD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 4mg BD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	SHR0302 4mg QD n=41 Participants Participants randomized in this arm will receive SHR0302 4mg QD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 4mg QD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	Placebo n=41 Participants Participants randomized in this arm will receive the placebo until week 8, and then will be re-randomized into one of the 3 active arms ( 4mg QD, 4mg BD, 8mg QD of SHR0302) in a 1:1:1 allocation ratio until the end of the study at week 16. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor). Placebos: Placebo Oral Tablet	Total n=164 Participants Total of all reporting groups
Age, Continuous	39.6 years STANDARD_DEVIATION 13.3 • n=5 Participants	40.3 years STANDARD_DEVIATION 12.3 • n=7 Participants	39.6 years STANDARD_DEVIATION 10.0 • n=5 Participants	42.7 years STANDARD_DEVIATION 12.9 • n=4 Participants	40.5 years STANDARD_DEVIATION 12.2 • n=21 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	15 Participants n=7 Participants	13 Participants n=5 Participants	22 Participants n=4 Participants	64 Participants n=21 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	26 Participants n=7 Participants	28 Participants n=5 Participants	19 Participants n=4 Participants	100 Participants n=21 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
Race (NIH/OMB) Asian	29 Participants n=5 Participants	25 Participants n=7 Participants	25 Participants n=5 Participants	24 Participants n=4 Participants	103 Participants n=21 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
Race (NIH/OMB) Black or African American	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
Race (NIH/OMB) White	12 Participants n=5 Participants	16 Participants n=7 Participants	16 Participants n=5 Participants	17 Participants n=4 Participants	61 Participants n=21 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
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
Time since initial primary diagnosis	5.05 years STANDARD_DEVIATION 4.16 • n=5 Participants	5.62 years STANDARD_DEVIATION 5.62 • n=7 Participants	5.17 years STANDARD_DEVIATION 5.17 • n=5 Participants	5.77 years STANDARD_DEVIATION 5.19 • n=4 Participants	5.40 years STANDARD_DEVIATION 5.03 • n=21 Participants

PRIMARY outcome

Timeframe: Week 8

Clinical response is defined as a decrease from baseline in a 9-point modified Mayo score of at least 2 points and at least 30%, with an accompanying reduction in the subscore for rectal bleeding of at least 1 point or absolute subscore for rectal bleeding of 0 or 1.

The 9-point modified Mayo score is the Mayo score excluding the Physician Global Assessment sub-score, hence the maximum is 9 points and the minimum is 0 point, includes:

Stool Frequency 0 = Normal

1. = 1-2 stools/day more than normal

2. = 3-4 stools/day more than normal

3. = 5 or more stools/day than normal

Rectal bleeding 0 = None

1. = Visible blood with stool less than half the time

2. = Visible blood with stool half of the time or more

3. = Passing blood alone

Mucosal appearance at endoscopy 0 = Normal or inactive disease

1. = Mild disease (erythema, decreased vascular pattern, mild friability

2. = Moderate disease (marked erythema, absent vascular pattern, friability, erosio

Outcome measures

Measure	SHR0302 8mg QD n=41 Participants Participants randomized in this arm will receive SHR0302 8mg QD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 8mg QD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	SHR0302 4mg BD n=41 Participants Participants randomized in this arm will receive SHR0302 4mg BD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 4mg BD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	SHR0302 4mg QD n=41 Participants Participants randomized in this arm will receive SHR0302 4mg QD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 4mg QD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	Placebo n=41 Participants Participants randomized in this arm will receive the placebo until week 8, and then will be re-randomized into one of the 3 active arms ( 4mg QD, 4mg BD, 8mg QD of SHR0302) in a 1:1:1 allocation ratio until the end of the study at week 16. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor). Placebos: Placebo Oral Tablet
The Percentage of Subject Achieve Clinical Response at Week 8	46.3 percentage of participants	46.3 percentage of participants	43.9 percentage of participants	26.8 percentage of participants

SECONDARY outcome

Timeframe: Week 8

Clinical remission was defined as a total Mayo score of 2 points or lower, with no individual sub-score exceeding 1 point. The percentage of subjects who achieve clinical remission per 9-point modified Mayo score at week 8, where stool frequency subscore ≤ 1, rectal bleeding subscore of 0, and endoscopic subscore ≤ 1.

9-point modified Mayo score includes: Stool Frequency 0 = Normal

1. = 1-2 stools/day more than normal

2. = 3-4 stools/day more than normal

3. = 5 or more stools/day than normal

Rectal bleeding 0 = None

1. = Visible blood with stool less than half the time

2. = Visible blood with stool half of the time or more

3. = Passing blood alone

Mucosal appearance at endoscopy 0 = Normal or inactive disease

1. = Mild disease (erythema, decreased vascular pattern, mild friability

2. = Moderate disease (marked erythema, absent vascular pattern, friability, erosions)

3. = Severe disease (spontaneous bleeding, ulceration)

Outcome measures

Measure	SHR0302 8mg QD n=41 Participants Participants randomized in this arm will receive SHR0302 8mg QD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 8mg QD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	SHR0302 4mg BD n=41 Participants Participants randomized in this arm will receive SHR0302 4mg BD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 4mg BD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	SHR0302 4mg QD n=41 Participants Participants randomized in this arm will receive SHR0302 4mg QD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 4mg QD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	Placebo n=41 Participants Participants randomized in this arm will receive the placebo until week 8, and then will be re-randomized into one of the 3 active arms ( 4mg QD, 4mg BD, 8mg QD of SHR0302) in a 1:1:1 allocation ratio until the end of the study at week 16. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor). Placebos: Placebo Oral Tablet
The Percentage of Subjects Achieve Clinical Remission	22.0 percentage of participants	24.4 percentage of participants	24.4 percentage of participants	4.9 percentage of participants

SECONDARY outcome

Timeframe: Week 8

Clinical remission was defined as a total Mayo score of 2 points or lower, with no individual sub-score exceeding 1 point. The percentage of subjects achieve clinical remission at week 8 as per a total Mayo score of 2 points or lower ≤2, with no individual subscore exceeding 1 point and a rectal bleeding subscore of 0.

The 9-point modified Mayo score includes:

Stool Frequency 0 = Normal

1. = 1-2 stools/day more than normal

2. = 3-4 stools/day more than normal

3. = 5 or more stools/day than normal

Rectal bleeding 0 = None

1. = Visible blood with stool less than half the time

2. = Visible blood with stool half of the time or more

3. = Passing blood alone

Mucosal appearance at endoscopy 0 = Normal or inactive disease

1. = Mild disease (erythema, decreased vascular pattern, mild friability

2. = Moderate disease (marked erythema, absent vascular patt

Outcome measures

Measure	SHR0302 8mg QD n=41 Participants Participants randomized in this arm will receive SHR0302 8mg QD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 8mg QD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	SHR0302 4mg BD n=41 Participants Participants randomized in this arm will receive SHR0302 4mg BD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 4mg BD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	SHR0302 4mg QD n=41 Participants Participants randomized in this arm will receive SHR0302 4mg QD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 4mg QD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	Placebo n=41 Participants Participants randomized in this arm will receive the placebo until week 8, and then will be re-randomized into one of the 3 active arms ( 4mg QD, 4mg BD, 8mg QD of SHR0302) in a 1:1:1 allocation ratio until the end of the study at week 16. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor). Placebos: Placebo Oral Tablet
The Percentage of Subjects Achieve Clinical Remission at Week 8	14.6 percentage of participants	17.1 percentage of participants	17.1 percentage of participants	2.4 percentage of participants

SECONDARY outcome

Timeframe: Week 8

Endoscopic remission was defined by Mayo endoscopic subscore ≤ 1 point. Mayo endoscopic subscore defines score 0 as normal or inactive disease, score 1 as mild disease (erythema, decreased vascular pattern, mild friability); score 2 as moderate disease (marked erythema, absent vascular pattern, friability, erosions)； score 3 as severe disease (spontaneous bleeding, ulceration).

Outcome measures

Measure	SHR0302 8mg QD n=41 Participants Participants randomized in this arm will receive SHR0302 8mg QD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 8mg QD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	SHR0302 4mg BD n=41 Participants Participants randomized in this arm will receive SHR0302 4mg BD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 4mg BD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	SHR0302 4mg QD n=41 Participants Participants randomized in this arm will receive SHR0302 4mg QD for the treatment phase. All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to continue to receive SHR0302 4mg QD. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	Placebo n=41 Participants Participants randomized in this arm will receive the placebo until week 8, and then will be re-randomized into one of the 3 active arms ( 4mg QD, 4mg BD, 8mg QD of SHR0302) in a 1:1:1 allocation ratio until the end of the study at week 16. Those who had completed the first 8-week of the treatment phase, but decided not to enter into the extension phase were also required to attend the 2-week follow-up visit. Participants who immaturely withdrew during the first treatment phase could not enter the extension phase. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor). Placebos: Placebo Oral Tablet
The Percentage of Subjects Achieve Endoscopic Remission (Mucosal Healing) at Week 8	26.8 percentage of participants	29.3 percentage of participants	36.6 percentage of participants	14.6 percentage of participants

Adverse Events

Treatment Phase-SHR0302 8mg QD

Serious events: 2 serious events

Other events: 13 other events

Deaths: 0 deaths

Treatment Phase-SHR0302 4mg BD

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Treatment Phase-SHR0302 4mg QD

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

Treatment Phase-Placebo

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Extension Phase-SHR0302 8mg QD → SHR0302 8mg QD

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Extension Phase-SHR0302 4mg BD → SHR0302 4mg BD

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Extension Phase-SHR0302 4mg QD → SHR0302 4mg QD

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Extension Phase-placebo → SHR0302 8mg QD

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Extension Phase-placebo → SHR0302 4mg BD

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Extension Phase-placebo → SHR0302 4mg QD

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Treatment Phase-SHR0302 8mg QD n=41 participants at risk Participants randomized in this arm will receive dose A of SHR0302 until the end of the study at week 16. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	Treatment Phase-SHR0302 4mg BD n=41 participants at risk Participants randomized in this arm will receive dose B of SHR0302 until the end of the study at week 16. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	Treatment Phase-SHR0302 4mg QD n=41 participants at risk Participants randomized in this arm will receive dose C of SHR0302 until the end of the study at week 16. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	Treatment Phase-Placebo n=41 participants at risk Participants randomized in this arm will receive placebo of SHR0302 until the end of the study at week 16. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	Extension Phase-SHR0302 8mg QD → SHR0302 8mg QD n=36 participants at risk All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (dose A, dose B, and dose C) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	Extension Phase-SHR0302 4mg BD → SHR0302 4mg BD n=39 participants at risk All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (dose A, dose B, and dose C) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	Extension Phase-SHR0302 4mg QD → SHR0302 4mg QD n=35 participants at risk All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (dose A, dose B, and dose C) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	Extension Phase-placebo → SHR0302 8mg QD n=11 participants at risk All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (dose A, dose B, and dose C) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	Extension Phase-placebo → SHR0302 4mg BD n=10 participants at risk All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (dose A, dose B, and dose C) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	Extension Phase-placebo → SHR0302 4mg QD n=13 participants at risk All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (dose A, dose B, and dose C) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Gastrointestinal disorders Colitis ulcerative	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	4.9% 2/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.8% 1/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	9.1% 1/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	10.0% 1/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Infections and infestations Anal abscess	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Infections and infestations Cytomegalovirus infection	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Infections and infestations Liver abscess	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Musculoskeletal and connective tissue disorders Synovitis	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.

Other adverse events

Measure	Treatment Phase-SHR0302 8mg QD n=41 participants at risk Participants randomized in this arm will receive dose A of SHR0302 until the end of the study at week 16. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	Treatment Phase-SHR0302 4mg BD n=41 participants at risk Participants randomized in this arm will receive dose B of SHR0302 until the end of the study at week 16. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	Treatment Phase-SHR0302 4mg QD n=41 participants at risk Participants randomized in this arm will receive dose C of SHR0302 until the end of the study at week 16. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	Treatment Phase-Placebo n=41 participants at risk Participants randomized in this arm will receive placebo of SHR0302 until the end of the study at week 16. SHR0302: The study drug, SHR0302, is designed to block the activity of an enzyme protein called JAK (known as a JAK inhibitor).	Extension Phase-SHR0302 8mg QD → SHR0302 8mg QD n=36 participants at risk All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (dose A, dose B, and dose C) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	Extension Phase-SHR0302 4mg BD → SHR0302 4mg BD n=39 participants at risk All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (dose A, dose B, and dose C) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	Extension Phase-SHR0302 4mg QD → SHR0302 4mg QD n=35 participants at risk All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (dose A, dose B, and dose C) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	Extension Phase-placebo → SHR0302 8mg QD n=11 participants at risk All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (dose A, dose B, and dose C) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	Extension Phase-placebo → SHR0302 4mg BD n=10 participants at risk All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (dose A, dose B, and dose C) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	Extension Phase-placebo → SHR0302 4mg QD n=13 participants at risk All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (dose A, dose B, and dose C) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Cardiac disorders Sinus bradycardia	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.8% 1/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	10.0% 1/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Gastrointestinal disorders Colitis ulcerative	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	4.9% 2/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.8% 1/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	5.1% 2/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.9% 1/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Blood and lymphatic system disorders Anaemia	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	12.2% 5/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	5.1% 2/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.9% 1/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	20.0% 2/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Blood and lymphatic system disorders Eosinophilia	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	9.1% 1/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Blood and lymphatic system disorders Erythropenia	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	9.1% 1/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	10.0% 1/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Blood and lymphatic system disorders Leukopenia	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	9.1% 1/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Infections and infestations Folliculitis	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.8% 1/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.6% 1/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	10.0% 1/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Infections and infestations Gastrointestinal infection	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.8% 1/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	10.0% 1/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Infections and infestations Influenza	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	10.0% 1/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Infections and infestations Nasopharyngitis	7.3% 3/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	4.9% 2/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Infections and infestations Upper respiratory tract infection	4.9% 2/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	4.9% 2/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	7.3% 3/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	5.6% 2/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	5.7% 2/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	7.7% 1/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Investigations Alanine aminotransferase increased	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	4.9% 2/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.9% 1/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	9.1% 1/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	10.0% 1/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Investigations Aspartate aminotransferase increased	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	5.6% 2/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.9% 1/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Investigations Bilirubin conjugated increased	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.8% 1/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	10.0% 1/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Investigations Blood bilirubin increased	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	5.6% 2/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	10.0% 1/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Investigations Blood bilirubin unconjugated increased	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	5.6% 2/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	10.0% 1/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Investigations Blood creatine phosphokinase increased	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.8% 1/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.6% 1/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.9% 1/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	7.7% 1/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Investigations Blood phosphorus decreased	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	9.1% 1/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Investigations Blood thyroid stimulating hormone decreased	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.9% 1/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	9.1% 1/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Investigations C-reactive protein increased	7.3% 3/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.8% 1/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Investigations Haematocrit decreased	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	9.1% 1/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Investigations Haemoglobin decreased	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	4.9% 2/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.8% 1/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	9.1% 1/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Investigations High density lipoprotein decreased	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	7.7% 1/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Investigations Lymphocyte count decreased	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.9% 1/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	7.7% 1/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Investigations Neutrophil count decreased	4.9% 2/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	5.6% 2/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.9% 1/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Investigations Neutrophil count increased	7.3% 3/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.8% 1/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.6% 1/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Investigations Platelet count decreased	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	7.7% 1/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Investigations Protein urine present	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.6% 1/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	5.7% 2/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Investigations Transaminases increased	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	5.6% 2/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.9% 1/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Investigations White blood cell count decreased	4.9% 2/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	11.1% 4/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.9% 1/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	10.0% 1/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Metabolism and nutrition disorders Hypercholesterolaemia	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	4.9% 2/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	9.1% 1/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.4% 1/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	2.9% 1/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	9.1% 1/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.
Reproductive system and breast disorders Sexual dysfunction	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/41 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/36 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/39 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/35 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/11 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	0.00% 0/10 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.	7.7% 1/13 • 18 weeks All participants that had completed the 8-week treatment phase (non-responders or responders) had the option to enter a blinded 8-week extension phase to receive the active drug. In the extension phase, participants randomized into placebo in the treatment phase were randomized into one of the three active groups above (4mg QD, 4mg BD, and 8mg QD) in a 1:1:1 ratio. Participants randomized to the active arms in the treatment phase remained in the same dose group in the extension phase.

Additional Information

Roger Liu, Medical Director

ReistoneBiopharma

Phone: +8613917512446

Email: roger.liu@reistonebio.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place