Trial Outcomes & Findings for A Study to Evaluate the Efficacy, Safety and Tolerability of Fixed Doses of Intranasal Esketamine in Japanese Participants With Treatment Resistant Depression (NCT NCT02918318)

Last Updated: 2025-04-29

Results Overview

MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition. Negative change in score indicates improvement.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

202 participants

Primary outcome timeframe

Baseline (Day 1) up to Day 28 (DB phase) induction

Results posted on

2025-04-29

Participant Flow

Participant milestones

Participant milestones
Measure	Esketamine 28 Milligrams (mg) Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 56 mg DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 84 mg DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Placebo DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.	Esketamine: Flexible Dose OL induction phase: Responders from the DB induction phase who relapsed in the postreatment phase entered in an open label extension phase and received induction with flexible intransal Esketamine (either 28 mg, 56 mg, or 84 mg) along with oral AD for 4 weeks. OL Follow-up phase: All participants who entered the OL induction phase are followed up in OL follow-up phase for 4 weeks.
Double-blind Induction Phase: 4 Weeks STARTED	41	40	41	80	0
Double-blind Induction Phase: 4 Weeks Responders	13	11	17	27	0
Double-blind Induction Phase: 4 Weeks COMPLETED	39	33	39	72	0
Double-blind Induction Phase: 4 Weeks NOT COMPLETED	2	7	2	8	0
Double-blind Follow-up Phase: 4 Weeks STARTED	27	28	24	53	0
Double-blind Follow-up Phase: 4 Weeks COMPLETED	26	28	23	50	0
Double-blind Follow-up Phase: 4 Weeks NOT COMPLETED	1	0	1	3	0
Posttreatment Phase: Up to 24 Weeks STARTED	13	11	17	27	0
Posttreatment Phase: Up to 24 Weeks COMPLETED	12	8	16	25	0
Posttreatment Phase: Up to 24 Weeks NOT COMPLETED	1	3	1	2	0
Open Label Treatment Phase: 4 Weeks STARTED	0	0	0	0	48
Open Label Treatment Phase: 4 Weeks COMPLETED	0	0	0	0	47
Open Label Treatment Phase: 4 Weeks NOT COMPLETED	0	0	0	0	1
Open Label Follow-up Phase: 4 Weeks STARTED	0	0	0	0	48
Open Label Follow-up Phase: 4 Weeks COMPLETED	0	0	0	0	47
Open Label Follow-up Phase: 4 Weeks NOT COMPLETED	0	0	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Esketamine 28 Milligrams (mg) Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 56 mg DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 84 mg DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Placebo DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.	Esketamine: Flexible Dose OL induction phase: Responders from the DB induction phase who relapsed in the postreatment phase entered in an open label extension phase and received induction with flexible intransal Esketamine (either 28 mg, 56 mg, or 84 mg) along with oral AD for 4 weeks. OL Follow-up phase: All participants who entered the OL induction phase are followed up in OL follow-up phase for 4 weeks.
Double-blind Induction Phase: 4 Weeks Adverse Event	1	4	2	3	0
Double-blind Induction Phase: 4 Weeks Lack of Efficacy	0	0	0	2	0
Double-blind Induction Phase: 4 Weeks Lost to Follow-up	0	0	0	1	0
Double-blind Induction Phase: 4 Weeks Withdrawal by Subject	1	1	0	0	0
Double-blind Induction Phase: 4 Weeks Non-compliance	0	0	0	1	0
Double-blind Induction Phase: 4 Weeks Other	0	2	0	1	0
Double-blind Follow-up Phase: 4 Weeks Withdrawal by Subject	0	0	0	2	0
Double-blind Follow-up Phase: 4 Weeks Adverse Event	1	0	1	1	0
Posttreatment Phase: Up to 24 Weeks Withdrawal by Subject	1	0	0	1	0
Posttreatment Phase: Up to 24 Weeks Other	0	3	1	1	0
Open Label Treatment Phase: 4 Weeks Adverse Event	0	0	0	0	1
Open Label Follow-up Phase: 4 Weeks Adverse Event	0	0	0	0	1

Baseline Characteristics

A Study to Evaluate the Efficacy, Safety and Tolerability of Fixed Doses of Intranasal Esketamine in Japanese Participants With Treatment Resistant Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Esketamine 28 Milligrams (mg) n=41 Participants Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 56 mg n=40 Participants DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 84 mg n=41 Participants DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Placebo n=80 Participants DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.	Total n=202 Participants Total of all reporting groups
Age, Continuous	45.9 years STANDARD_DEVIATION 9.97 • n=5 Participants	42.5 years STANDARD_DEVIATION 8.36 • n=7 Participants	41.9 years STANDARD_DEVIATION 10.26 • n=5 Participants	43.3 years STANDARD_DEVIATION 11.4 • n=4 Participants	43.4 years STANDARD_DEVIATION 10.35 • n=21 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	16 Participants n=7 Participants	18 Participants n=5 Participants	39 Participants n=4 Participants	96 Participants n=21 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	24 Participants n=7 Participants	23 Participants n=5 Participants	41 Participants n=4 Participants	106 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	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
Ethnicity (NIH/OMB) Not Hispanic or Latino	41 Participants n=5 Participants	40 Participants n=7 Participants	41 Participants n=5 Participants	80 Participants n=4 Participants	202 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
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	41 Participants n=5 Participants	40 Participants n=7 Participants	41 Participants n=5 Participants	80 Participants n=4 Participants	202 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	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) 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
Region of Enrollment JAPAN	41 Participants n=5 Participants	40 Participants n=7 Participants	41 Participants n=5 Participants	80 Participants n=4 Participants	202 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) up to Day 28 (DB phase) induction

Population: Full analysis set (FAS \[DB\]) included all randomized participants who received at least 1 dose of intranasal study agent during the DB induction phase. Here, N (Number of participants analyzed) signifies those participants who were evaluable for this outcome measure (OM).

Outcome measures

Outcome measures
Measure	Esketamine 28 Milligrams (mg) n=39 Participants Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 56 mg n=34 Participants DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 84 mg n=39 Participants DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Placebo n=72 Participants DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
Double-Blind (DB) Induction Phase: Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score up to Day 28	-15.2 Units on a scale Standard Deviation 13.07	-14.5 Units on a scale Standard Deviation 10.53	-15.1 Units on a scale Standard Deviation 12.21	-15.3 Units on a scale Standard Deviation 11.68

SECONDARY outcome

Timeframe: Days 2, 8, 15, 22 and 28 (DB induction phase)

Population: FAS (DB) included all randomized participants who received at least 1 dose of intranasal study agent during the DB induction phase. Here 'n' (number analyzed) signifies number of participants who were evaluable for this OM at specified timepoints.

A participant is defined as responder (yes=1 and no=0) at a given time point if the percent improvement from baseline in MADRS is greater than or equal to (\>=) 50 percent (%). MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.

Outcome measures

Outcome measures
Measure	Esketamine 28 Milligrams (mg) n=41 Participants Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 56 mg n=40 Participants DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 84 mg n=41 Participants DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Placebo n=80 Participants DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
DB Induction Phase: Percentage of Participants With Response Based on MADRS Total Score Day 2	22.0 Percentage of participants	13.2 Percentage of participants	10.0 Percentage of participants	9.0 Percentage of participants
DB Induction Phase: Percentage of Participants With Response Based on MADRS Total Score Day 8	2.4 Percentage of participants	2.6 Percentage of participants	9.8 Percentage of participants	3.8 Percentage of participants
DB Induction Phase: Percentage of Participants With Response Based on MADRS Total Score Day 15	17.5 Percentage of participants	8.3 Percentage of participants	15.0 Percentage of participants	18.2 Percentage of participants
DB Induction Phase: Percentage of Participants With Response Based on MADRS Total Score Day 22	23.1 Percentage of participants	13.9 Percentage of participants	20.5 Percentage of participants	29.7 Percentage of participants
DB Induction Phase: Percentage of Participants With Response Based on MADRS Total Score Day 28	33.3 Percentage of participants	35.3 Percentage of participants	43.6 Percentage of participants	37.5 Percentage of participants

SECONDARY outcome

Timeframe: Days 2, 8, 15, 22 and 28 (DB induction phase)

Population: FAS (DB) included all randomized defined as all participants who received at least 1 dose of intranasal study agent during the DB induction phase. Here 'n' (number analyzed) signifies number of participants who were evaluable for this OM at specified timepoints.

A participant was considered in remission at a given time point if the MADRS total score \<=12. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.

Outcome measures

Outcome measures
Measure	Esketamine 28 Milligrams (mg) n=41 Participants Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 56 mg n=40 Participants DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 84 mg n=41 Participants DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Placebo n=80 Participants DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
DB Induction Phase: Percentage of Participants With Remission Based on MADRS Total Score Day 2	9.8 Percentage of participants	0 Percentage of participants	7.5 Percentage of participants	3.8 Percentage of participants
DB Induction Phase: Percentage of Participants With Remission Based on MADRS Total Score Day 8	2.4 Percentage of participants	0 Percentage of participants	4.9 Percentage of participants	1.3 Percentage of participants
DB Induction Phase: Percentage of Participants With Remission Based on MADRS Total Score Day 15	7.5 Percentage of participants	2.8 Percentage of participants	10.0 Percentage of participants	3.9 Percentage of participants
DB Induction Phase: Percentage of Participants With Remission Based on MADRS Total Score Day 22	10.3 Percentage of participants	5.6 Percentage of participants	7.7 Percentage of participants	14.9 Percentage of participants
DB Induction Phase: Percentage of Participants With Remission Based on MADRS Total Score Day 28	23.1 Percentage of participants	11.8 Percentage of participants	23.1 Percentage of participants	20.8 Percentage of participants

SECONDARY outcome

Timeframe: Day 2 up to Day 28 (DB induction phase)

Population: FAS (DB) included all randomized participants who received at least 1 dose of intranasal study agent during DB induction phase. Participants with missed assessments or discontinued early were not considered to have onset of clinical response. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this OM.

A participant was defined as having a clinical response if there was at least 50% improvement from baseline in the MADRS total score with onset by Day 2 that was maintained to Day 28 in DB induction phase. Participants were allowed one excursion (non-response) on Days 8, 15 or 22, provided the score is at least 25% improvement. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.

Outcome measures

Outcome measures
Measure	Esketamine 28 Milligrams (mg) n=41 Participants Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 56 mg n=39 Participants DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 84 mg n=41 Participants DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Placebo n=79 Participants DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
DB Induction Phase: Percentage of Participants Showing Onset of Clinical Response Onset of clinical response: Yes	2.4 Percentage of participants	2.6 Percentage of participants	7.3 Percentage of participants	6.3 Percentage of participants
DB Induction Phase: Percentage of Participants Showing Onset of Clinical Response Onset of clinical response: No	97.6 Percentage of participants	97.4 Percentage of participants	92.7 Percentage of participants	93.7 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) up to Day 28 (DB induction pahse)

Population: FAS (DB) included all randomized participants who received at least 1 dose of intranasal study agent during the DB induction phase. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this OM.

CGI-S provides measure of severity of participant's illness including participant's history, psychosocial circumstances, symptoms, behavior and impact of symptoms on ability to function. CGI-S evaluates severity of psychopathology on scale of 0 to 7. Considering total clinical experience, participant is assessed on severity of mental illness according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among most extremely ill patients. Values of 0 (not assessed) were excluded from analysis. CGI-S permits global evaluation of participant's condition at given time.

Outcome measures

Outcome measures
Measure	Esketamine 28 Milligrams (mg) n=39 Participants Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 56 mg n=33 Participants DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 84 mg n=39 Participants DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Placebo n=72 Participants DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
DB Induction Phase: Change From Baseline in Clinical Global Impression - Severity (CGI-S) Total Score up to Day 28	-1.0 Units on a scale Interval -5.0 to 1.0	-1.0 Units on a scale Interval -3.0 to 0.0	-1.0 Units on a scale Interval -5.0 to 0.0	-1.0 Units on a scale Interval -4.0 to 1.0

SECONDARY outcome

Timeframe: Baseline (Day 1) up to Day 28 (DB induction phase)

Population: FAS included all randomized participants who received at least 1 dose of intranasal study agent during the DB induction phase. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this OM.

GAD-7 was a brief and validated 7-item self-report assessment of overall anxiety. Participants respond to each item using a 4-point scale with response categories of 0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day. Item responses are summed to yield a total score with a range of 0 to 21, where higher scores indicate more anxiety. The recall period is 2 weeks. The severity of the GAD-7 is categorized as follows: None (0-4), Mild (5-9), Moderate (10-14) and Severe (15 -21).

Outcome measures

Outcome measures
Measure	Esketamine 28 Milligrams (mg) n=39 Participants Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 56 mg n=35 Participants DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 84 mg n=39 Participants DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Placebo n=73 Participants DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
DB Induction Phase: Change From Baseline in Generalized Anxiety Disorder 7-Item Scale (GAD-7) up to Day 28	-8.2 Units on a scale Standard Deviation 4.94	-7.8 Units on a scale Standard Deviation 5.05	-8.1 Units on a scale Standard Deviation 5.67	-7.7 Units on a scale Standard Deviation 5.05

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 28 (DB induction phase)

SDS is a participant-reported outcome measure and 5 item questionnaire used for assessment of functional impairment and associated disability. First three items assess disruption of 1 work/school, 2 social life, 3 family life/home responsibilities using a 0(no impairment)-10 (most severe impairment). Score for first 3 items are summed to create total score of 0-30 where higher score indicates greater impairment and a negative change in score indicates improvement. It also has one item on days lost from school or work and one item on days when under productive.

Outcome measures

Outcome measures
Measure	Esketamine 28 Milligrams (mg) n=30 Participants Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 56 mg n=29 Participants DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 84 mg n=31 Participants DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Placebo n=53 Participants DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
DB Induction Phase: Change From Baseline in Sheehan Disability Scale (SDS) Total Score up to Day 28	-8.6 Units on a scale Standard Deviation 8.68	-7.9 Units on a scale Standard Deviation 7.94	-9.5 Units on a scale Standard Deviation 8.93	-7.0 Units on a scale Standard Deviation 7.39

SECONDARY outcome

Timeframe: From EndPoint (last post baseline assessment value during the DB induction phase [up to Day 28]) up to 24 weeks (posttreatment phase)

Population: Population included participants with remit at the end of DB.

Time to relapse in participants with remission at the end of the double-blind phase was defined as the time between induction phase and the first documentation of a relapse event during the posttreatment phase. Relapse was defined as any of the following: 1) MADRS total score \>= 22 for 2 consecutive assessments. The date of the second MADRS assessment was used for the date of relapse; 2) Hospitalization for worsening depression or any other clinically relevant event determined per clinical judgment to be suggestive of relapse of depressive illness like suicide attempt, completed suicide, or hospitalization for suicide prevention. If hospitalized for any of these events, start date of hospitalization was used as relapse date. If participant was not hospitalized, event date was used. 3) If both relapse criteria were met, earlier date was defined as date of relapse. Remission was defined as MADRS total score \<=12.

Outcome measures

Outcome measures
Measure	Esketamine 28 Milligrams (mg) n=9 Participants Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 56 mg n=4 Participants DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 84 mg n=9 Participants DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Placebo n=15 Participants DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
Posttreatment Phase: Time to Relapse in Participants With Remission (MADRS Total Score <=12)	34.0 Days Interval 26.0 to Upper limit of 90 % confidence internal was not estimable due to insufficient number of participants with events.	52.0 Days Interval 20.0 to 80.0	37.0 Days Interval 19.0 to 71.0	30.0 Days Interval 22.0 to 50.0

SECONDARY outcome

Timeframe: From EndPoint (last post baseline assessment value during the DB induction phase [up to Day 28]) up to 24 weeks (posttreatment phase)

Population: Population included participants with response (not remit) at the end of DB.

Time to relapse in participants with response (\>=50% reduction from baseline in MADRS total score) but who are not in remission was reported. Relapse is defined as any of the following: 1) MADRS total score \>= 22 for 2 consecutive assessments. The date of the second MADRS assessment was used for the date of relapse. 2)Hospitalization for worsening depression or any other clinically relevant event determined per clinical judgment to be suggestive of relapse of depressive illness like suicide attempt, completed suicide, or hospitalization for suicide prevention. If hospitalized for any of these events, start date of hospitalization was used as relapse date. If participant was not hospitalized, event date was used. 3) If both relapse criteria were met, earlier date was defined as date of relapse. Remission was defined as MADRS total score \<=12.

Outcome measures

Outcome measures
Measure	Esketamine 28 Milligrams (mg) n=13 Participants Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 56 mg n=11 Participants DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 84 mg n=17 Participants DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Placebo n=27 Participants DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
Posttreatment Phase: Time to Relapse in Participants With Response (>=50% Reduction From Baseline in MADRS Total Score) But Who Are Not in Remission	32.0 Days Interval 13.0 to 44.0	26.0 Days Interval 9.0 to 121.0	79.5 Days Interval 16.0 to 108.0	91.0 Days Interval 22.0 to Upper limit of 90 % confidence internal was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Baseline (DB induction phase), Weeks 2, 4, 6, 8, 12, 16, 20 and 24 (posttreatment phase)

Population: Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this OM. Here, 'n' (number analyzed) signifies number of participants who were evaluable for this OM at specified timepoints.

SDS is a participant-reported outcome measure and is a 5-item questionnaire which has been widely used and accepted for assessment of functional impairment and associated disability. The first three items assess disruption of (1) work/school, (2) social life, and (3) family life/home responsibilities using a 0-10 rating scale. The score for the first three items are summed to create a total score of 0-30, where a higher score indicates greater impairment. It also has one item on days lost from school or work and one item on days when under productive. FAS (responders): All randomized participants who received at least 1 dose of intranasal study medication during DB induction phase and who were responders at the end of DB induction phase and entered posttreatment phase

Outcome measures

Outcome measures
Measure	Esketamine 28 Milligrams (mg) n=8 Participants Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 56 mg n=10 Participants DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 84 mg n=13 Participants DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Placebo n=18 Participants DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
Posttreatment Phase: Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 2, 4, 6, 8, 12, 16, 20 and 24 Week 6	-17.7 Units on a scale Standard Deviation 8.50	-11.0 Units on a scale Standard Deviation 3.61	-14.6 Units on a scale Standard Deviation 5.53	-12.0 Units on a scale Standard Deviation 4.39
Posttreatment Phase: Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 2, 4, 6, 8, 12, 16, 20 and 24 Week 8	-12.0 Units on a scale Standard Deviation 14.42	-13.3 Units on a scale Standard Deviation 1.53	-15.3 Units on a scale Standard Deviation 7.15	-11.4 Units on a scale Standard Deviation 6.02
Posttreatment Phase: Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 2, 4, 6, 8, 12, 16, 20 and 24 Week 12	-20.5 Units on a scale Standard Deviation 3.54	-13.0 Units on a scale Standard Deviation 7.21	-18.3 Units on a scale Standard Deviation 7.76	-14.8 Units on a scale Standard Deviation 4.88
Posttreatment Phase: Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 2, 4, 6, 8, 12, 16, 20 and 24 Week 16	-21.5 Units on a scale Standard Deviation 6.36	-17.5 Units on a scale Standard Deviation 0.71	-12.5 Units on a scale Standard Deviation 21.92	-15.8 Units on a scale Standard Deviation 1.89
Posttreatment Phase: Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 2, 4, 6, 8, 12, 16, 20 and 24 Week 20	-22.0 Units on a scale Standard Deviation 7.07	-18.0 Units on a scale	-28.0 Units on a scale	-14.0 Units on a scale Standard Deviation 3.65
Posttreatment Phase: Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 2, 4, 6, 8, 12, 16, 20 and 24 Week 24	-21.5 Units on a scale Standard Deviation 4.95	-16.0 Units on a scale	-28.0 Units on a scale	-14.8 Units on a scale Standard Deviation 3.59
Posttreatment Phase: Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 2, 4, 6, 8, 12, 16, 20 and 24 Week 2	-14.6 Units on a scale Standard Deviation 7.82	-8.1 Units on a scale Standard Deviation 6.15	-13.1 Units on a scale Standard Deviation 7.65	-11.2 Units on a scale Standard Deviation 6.83
Posttreatment Phase: Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 2, 4, 6, 8, 12, 16, 20 and 24 Week 4	-12.9 Units on a scale Standard Deviation 5.69	-8.3 Units on a scale Standard Deviation 2.75	-13.6 Units on a scale Standard Deviation 7.34	-9.8 Units on a scale Standard Deviation 5.84

SECONDARY outcome

Timeframe: Days 8, 15, 22 and 28 (OL induction phase)

Population: FAS (OL) included all randomized participants who received at least 1 dose of intranasal study agent during the OL induction phase. Here 'n' (Number analyzed) signifies number of participants who were evaluable for this OM at specified timepoints.

Outcome measures

Outcome measures
Measure	Esketamine 28 Milligrams (mg) n=48 Participants Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 56 mg DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 84 mg DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Placebo DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
OL Induction Phase: Percentage of Participants With Remission Based on MADRS Total Score Day 8	14.6 Percentage of participants	—	—	—
OL Induction Phase: Percentage of Participants With Remission Based on MADRS Total Score Day 15	23.4 Percentage of participants	—	—	—
OL Induction Phase: Percentage of Participants With Remission Based on MADRS Total Score Day 22	31.9 Percentage of participants	—	—	—
OL Induction Phase: Percentage of Participants With Remission Based on MADRS Total Score Day 28	42.6 Percentage of participants	—	—	—

SECONDARY outcome

Timeframe: Baseline (Prior to first Dose of OL induction phase on Day 1) up to endpoint of OL induction phase (last post baseline assessment value during OL induction phase [OL: up to Day 28])

Population: FAS (OL) included all participants who received at least 1 dose of intranasal study agent during the OL induction phase.

Outcome measures

Outcome measures
Measure	Esketamine 28 Milligrams (mg) n=48 Participants Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 56 mg DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 84 mg DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Placebo DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
OL Induction Phase: Change From Baseline (Prior to the First Dose of OL Induction Phase) in MADRS Total Score up to Endpoint OL Induction Phase (Last Post Baseline Assessment Value During the OL Induction Phase [OL: up to Day 28]) Baseline	16.1 Units on a scale Standard Deviation 9.47	—	—	—
OL Induction Phase: Change From Baseline (Prior to the First Dose of OL Induction Phase) in MADRS Total Score up to Endpoint OL Induction Phase (Last Post Baseline Assessment Value During the OL Induction Phase [OL: up to Day 28]) Change from baseline	-14.5 Units on a scale Standard Deviation 11.06	—	—	—

SECONDARY outcome

Timeframe: Baseline (Prior to first dose of OL induction phase on Day 1), endpoint of OL induction phase (last post baseline assessment value during the OL induction phase [OL: up to Day 28])

Population: FAS (OL) included all participants who received at least 1 dose of intranasal study agent during the OL induction phase.

CGI-S provides measure of severity of participant's illness including participant's history, psychosocial circumstances, symptoms, behavior and impact of symptoms on ability to function. CGI-S evaluates severity of psychopathology on scale of 0 to 7. Considering total clinical experience, participant is assessed on severity of mental illness according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among most extremely ill patients. CGI-S permits global evaluation of participant's condition at given time.

Outcome measures

Outcome measures
Measure	Esketamine 28 Milligrams (mg) n=48 Participants Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 56 mg DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Esketamine 84 mg DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.	Placebo DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had \>=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
OL Induction Phase: Percentage of Participants With Severity of Psychopathology on the CGI-S Scale Among the most extremely ill patients:Endpoint	0 Percentage of participants	—	—	—
OL Induction Phase: Percentage of Participants With Severity of Psychopathology on the CGI-S Scale Normal, not at all ill:Baseline	0 Percentage of participants	—	—	—
OL Induction Phase: Percentage of Participants With Severity of Psychopathology on the CGI-S Scale Normal, not at all ill:Endpoint	14.6 Percentage of participants	—	—	—
OL Induction Phase: Percentage of Participants With Severity of Psychopathology on the CGI-S Scale Borderline mentally ill:Baseline	0 Percentage of participants	—	—	—
OL Induction Phase: Percentage of Participants With Severity of Psychopathology on the CGI-S Scale Borderline mentally ill:Endpoint	16.7 Percentage of participants	—	—	—
OL Induction Phase: Percentage of Participants With Severity of Psychopathology on the CGI-S Scale Mildly ill:Baseline	4.2 Percentage of participants	—	—	—
OL Induction Phase: Percentage of Participants With Severity of Psychopathology on the CGI-S Scale Mildly ill:Endpoint	43.8 Percentage of participants	—	—	—
OL Induction Phase: Percentage of Participants With Severity of Psychopathology on the CGI-S Scale Moderately ill:Baseline	75.0 Percentage of participants	—	—	—
OL Induction Phase: Percentage of Participants With Severity of Psychopathology on the CGI-S Scale Moderately ill:Endpoint	20.8 Percentage of participants	—	—	—
OL Induction Phase: Percentage of Participants With Severity of Psychopathology on the CGI-S Scale Markedly ill:Baseline	14.6 Percentage of participants	—	—	—
OL Induction Phase: Percentage of Participants With Severity of Psychopathology on the CGI-S Scale Markedly ill:Endpoint	4.2 Percentage of participants	—	—	—
OL Induction Phase: Percentage of Participants With Severity of Psychopathology on the CGI-S Scale Severely ill:Baseline	4.2 Percentage of participants	—	—	—
OL Induction Phase: Percentage of Participants With Severity of Psychopathology on the CGI-S Scale Severely ill:Endpoint	0 Percentage of participants	—	—	—
OL Induction Phase: Percentage of Participants With Severity of Psychopathology on the CGI-S Scale Among the most extremely ill patients:Baseline	2.1 Percentage of participants	—	—	—

Adverse Events

Double Blind (DB): Esketamine 28 mg

Serious events: 1 serious events

Other events: 33 other events

Deaths: 0 deaths

DB: Esketamine 56 mg

Serious events: 0 serious events

Other events: 39 other events

Deaths: 0 deaths

DB: Esketamine 84 mg

Serious events: 1 serious events

Other events: 39 other events

Deaths: 0 deaths

DB: Placebo

Serious events: 1 serious events

Other events: 34 other events

Deaths: 0 deaths

DB Follow Up (FU): Esketamine 28 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

DB FU: Esketamine 56 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

DB FU: Esketamine 84 mg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

DB FU: Placebo

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Post-Treatment (PT) Phase: Esketamine 28 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

PT Phase: Esketamine 56 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

PT Phase: Esketamine 84 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

PT Phase: Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Open-Label (OL): Flexible Esketamine

Serious events: 1 serious events

Other events: 47 other events

Deaths: 0 deaths

OL FU: Flexible Esketamine

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Double Blind (DB): Esketamine 28 mg n=41 participants at risk Participants received intranasal esketamine 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Analysis was performed on safety analysis set- all randomized participants who received at least 1 dose of Esk during DB induction phase.	DB: Esketamine 56 mg n=41 participants at risk Participants received intranasal esketamine 56 mg twice a week add-on to an oral AD for 4 weeks. Analysis was performed on safety analysis set- all randomized participants who received at least 1 dose of Esk DB induction phase.	DB: Esketamine 84 mg n=40 participants at risk Participants received intranasal esketamine 84 mg twice a week add-on to an oral AD for 4 weeks. Analysis was performed on safety analysis set- all randomized participants who received at least 1 dose of Esk during DB induction phase.	DB: Placebo n=80 participants at risk Participants received intranasal placebo twice a week add-on to an oral AD for 4 weeks. Analysis was performed on safety analysis set- all randomized participants who received dose of internasal placebo during DB induction phase.	DB Follow Up (FU): Esketamine 28 mg n=27 participants at risk Participants who were non responders at the end of DB induction phase and entered the DB follow-up phase received only oral AD for 4 weeks. Analysis was performed on follow-up analysis set- all participants who entered the follow-up phase and were evaluated for the safety.	DB FU: Esketamine 56 mg n=29 participants at risk Participants who were non responders at the end of DB induction phase and entered the DB follow-up phase received only oral AD in the DB FU phase. Analysis was performed on follow-up analysis set- all participants who entered the follow-up phase and were evaluated for the safety.	DB FU: Esketamine 84 mg n=23 participants at risk Participants who were non responders at the end of DB induction phase and entered the DB follow-up phase received only oral AD in the DB FU phase. Analysis was performed on follow-up analysis set- all participants who entered the follow-up phase and were evaluated for the safety.	DB FU: Placebo n=53 participants at risk Participants who were non responders at the end of DB induction phase and entered the DB follow-up phase received only oral AD in the DB FU phase. Analysis was performed on follow-up analysis set- all participants who entered the follow-up phase and were evaluated for the safety.	Post-Treatment (PT) Phase: Esketamine 28 mg n=13 participants at risk Participants who were responders at the end of DB induction phase and entered in the PT phase received only oral AD in the PT phase. Analysis was performed on safety analysis set- All participants who received at least 1 dose of oral AD during PT phase.	PT Phase: Esketamine 56 mg n=11 participants at risk Participants who were responders at the end of DB induction phase and entered in the PT phase received only oral AD in the PT phase. Analysis was performed on safety analysis set- All participants who received at least 1 dose of oral AD during PT phase.	PT Phase: Esketamine 84 mg n=17 participants at risk Participants who were responders at the end of DB induction phase and entered in the PT phase received only an oral AD in the PT phase. Analysis was performed on safety analysis set- All participants who received at least 1 dose of oral AD during PT phase.	PT Phase: Placebo n=27 participants at risk Participants who were responders at the end of DB induction phase and entered in the PT phase received only oral AD in the PT phase. Analysis was performed on safety analysis set- All participants who received at least 1 dose of oral AD during PT phase.	Open-Label (OL): Flexible Esketamine n=48 participants at risk Participants received flexible esketamine add-on to an oral AD during OL induction phase for 4 weeks. Analysis was performed on safety analysis set- All participants who received at least 1 dose of flexible Esk during OL induction phase.	OL FU: Flexible Esketamine n=48 participants at risk Participants who received flexible esketamine add-on to an oral AD during OL induction phase were followed for 4 weeks in OL FU phase. Analysis was performed on follow-up analysis set- all participants who entered the OL follow-up phase and were evaluated for the safety.
Cardiac disorders Atrioventricular Block Second Degree	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.1% 1/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Injury, poisoning and procedural complications Ankle Fracture	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	1.9% 1/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Injury, poisoning and procedural complications Fracture	2.4% 1/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Musculoskeletal and connective tissue disorders Muscular Weakness	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	4.3% 1/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine Leiomyoma	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.1% 1/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Nervous system disorders Cerebral Disorder	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	4.3% 1/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Psychiatric disorders Suicidal Ideation	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.5% 1/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	1.2% 1/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Psychiatric disorders Suicide Attempt	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	1.9% 1/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.1% 1/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.

Other adverse events

Other adverse events
Measure	Double Blind (DB): Esketamine 28 mg n=41 participants at risk Participants received intranasal esketamine 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Analysis was performed on safety analysis set- all randomized participants who received at least 1 dose of Esk during DB induction phase.	DB: Esketamine 56 mg n=41 participants at risk Participants received intranasal esketamine 56 mg twice a week add-on to an oral AD for 4 weeks. Analysis was performed on safety analysis set- all randomized participants who received at least 1 dose of Esk DB induction phase.	DB: Esketamine 84 mg n=40 participants at risk Participants received intranasal esketamine 84 mg twice a week add-on to an oral AD for 4 weeks. Analysis was performed on safety analysis set- all randomized participants who received at least 1 dose of Esk during DB induction phase.	DB: Placebo n=80 participants at risk Participants received intranasal placebo twice a week add-on to an oral AD for 4 weeks. Analysis was performed on safety analysis set- all randomized participants who received dose of internasal placebo during DB induction phase.	DB Follow Up (FU): Esketamine 28 mg n=27 participants at risk Participants who were non responders at the end of DB induction phase and entered the DB follow-up phase received only oral AD for 4 weeks. Analysis was performed on follow-up analysis set- all participants who entered the follow-up phase and were evaluated for the safety.	DB FU: Esketamine 56 mg n=29 participants at risk Participants who were non responders at the end of DB induction phase and entered the DB follow-up phase received only oral AD in the DB FU phase. Analysis was performed on follow-up analysis set- all participants who entered the follow-up phase and were evaluated for the safety.	DB FU: Esketamine 84 mg n=23 participants at risk Participants who were non responders at the end of DB induction phase and entered the DB follow-up phase received only oral AD in the DB FU phase. Analysis was performed on follow-up analysis set- all participants who entered the follow-up phase and were evaluated for the safety.	DB FU: Placebo n=53 participants at risk Participants who were non responders at the end of DB induction phase and entered the DB follow-up phase received only oral AD in the DB FU phase. Analysis was performed on follow-up analysis set- all participants who entered the follow-up phase and were evaluated for the safety.	Post-Treatment (PT) Phase: Esketamine 28 mg n=13 participants at risk Participants who were responders at the end of DB induction phase and entered in the PT phase received only oral AD in the PT phase. Analysis was performed on safety analysis set- All participants who received at least 1 dose of oral AD during PT phase.	PT Phase: Esketamine 56 mg n=11 participants at risk Participants who were responders at the end of DB induction phase and entered in the PT phase received only oral AD in the PT phase. Analysis was performed on safety analysis set- All participants who received at least 1 dose of oral AD during PT phase.	PT Phase: Esketamine 84 mg n=17 participants at risk Participants who were responders at the end of DB induction phase and entered in the PT phase received only an oral AD in the PT phase. Analysis was performed on safety analysis set- All participants who received at least 1 dose of oral AD during PT phase.	PT Phase: Placebo n=27 participants at risk Participants who were responders at the end of DB induction phase and entered in the PT phase received only oral AD in the PT phase. Analysis was performed on safety analysis set- All participants who received at least 1 dose of oral AD during PT phase.	Open-Label (OL): Flexible Esketamine n=48 participants at risk Participants received flexible esketamine add-on to an oral AD during OL induction phase for 4 weeks. Analysis was performed on safety analysis set- All participants who received at least 1 dose of flexible Esk during OL induction phase.	OL FU: Flexible Esketamine n=48 participants at risk Participants who received flexible esketamine add-on to an oral AD during OL induction phase were followed for 4 weeks in OL FU phase. Analysis was performed on follow-up analysis set- all participants who entered the OL follow-up phase and were evaluated for the safety.
Gastrointestinal disorders Vomiting	2.4% 1/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	7.3% 3/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	10.0% 4/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	3.8% 3/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	3.4% 1/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	4.2% 2/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Psychiatric disorders Euphoric Mood	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	9.8% 4/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	7.5% 3/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	8.3% 4/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Psychiatric disorders Hallucination	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.4% 1/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.0% 2/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.1% 1/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Cardiac disorders Palpitations	2.4% 1/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	4.9% 2/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.0% 2/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	1.2% 1/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	1.9% 1/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	7.7% 1/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Ear and labyrinth disorders Hyperacusis	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.4% 1/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.0% 2/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.1% 1/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Ear and labyrinth disorders Tinnitus	2.4% 1/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.0% 2/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.1% 1/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Ear and labyrinth disorders Vertigo	9.8% 4/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	17.1% 7/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	20.0% 8/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	1.2% 1/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	12.5% 6/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Eye disorders Conjunctivitis Allergic	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	7.7% 1/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Eye disorders Diplopia	2.4% 1/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	7.3% 3/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.1% 1/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Eye disorders Dry Eye	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.4% 1/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	9.1% 1/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Eye disorders Visual Impairment	2.4% 1/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	4.9% 2/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	6.2% 3/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Gastrointestinal disorders Diarrhoea	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	9.8% 4/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.0% 2/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	3.8% 3/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	1.9% 1/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	9.1% 1/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Gastrointestinal disorders Hypoaesthesia Oral	7.3% 3/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	4.9% 2/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.0% 2/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	8.3% 4/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Gastrointestinal disorders Nausea	17.1% 7/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	17.1% 7/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	20.0% 8/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	8.8% 7/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	3.8% 2/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	25.0% 12/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Gastrointestinal disorders Stomatitis	4.9% 2/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.4% 1/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.9% 1/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	3.7% 1/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
General disorders Asthenia	4.9% 2/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	17.1% 7/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	7.5% 3/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.9% 1/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	6.2% 3/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
General disorders Feeling Drunk	2.4% 1/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	12.2% 5/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.0% 2/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	1.2% 1/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	14.6% 7/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
General disorders Malaise	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	7.3% 3/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	7.5% 3/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	6.2% 3/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
General disorders Thirst	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.0% 2/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Infections and infestations Nasopharyngitis	2.4% 1/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.5% 1/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	3.8% 3/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	7.4% 2/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	3.4% 1/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	4.3% 1/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.7% 3/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	15.4% 2/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	18.2% 2/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	11.8% 2/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	11.1% 3/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	4.2% 2/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	4.2% 2/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Injury, poisoning and procedural complications Muscle Strain	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	7.7% 1/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Investigations Blood Pressure Diastolic Increased	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.0% 2/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.5% 2/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Investigations Blood Pressure Increased	29.3% 12/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	46.3% 19/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	47.5% 19/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	10.0% 8/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	50.0% 24/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Investigations Respiratory Rate Decreased	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.0% 2/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Investigations Weight Increased	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.0% 2/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Musculoskeletal and connective tissue disorders Muscular Weakness	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	4.9% 2/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.0% 2/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	4.3% 1/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	1.9% 1/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.1% 1/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Nervous system disorders Dizziness	26.8% 11/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	43.9% 18/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	37.5% 15/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	6.2% 5/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	3.7% 1/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	3.4% 1/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	1.9% 1/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	7.7% 1/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	43.8% 21/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Nervous system disorders Dizziness Postural	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	7.3% 3/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.0% 2/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.9% 1/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.1% 1/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Nervous system disorders Dysarthria	2.4% 1/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.0% 2/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	1.9% 1/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.1% 1/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Nervous system disorders Dyslalia	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.0% 2/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.1% 1/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Nervous system disorders Headache	14.6% 6/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	12.2% 5/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	10.0% 4/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	3.8% 3/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	4.3% 1/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.9% 1/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	7.4% 2/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	16.7% 8/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Nervous system disorders Hypoaesthesia	17.1% 7/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	19.5% 8/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	12.5% 5/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.0% 4/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	12.5% 6/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.1% 1/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Nervous system disorders Hypotonia	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	7.5% 3/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.1% 1/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Nervous system disorders Mental Impairment	7.3% 3/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	4.9% 2/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	4.2% 2/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Nervous system disorders Sedation	2.4% 1/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	9.8% 4/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	12.5% 5/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	12.5% 6/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Nervous system disorders Somnolence	24.4% 10/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	31.7% 13/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	27.5% 11/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	17.5% 14/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	1.9% 1/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	7.7% 1/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	22.9% 11/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Psychiatric disorders Agitation	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	9.1% 1/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Psychiatric disorders Anxiety	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	4.9% 2/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.5% 1/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	1.2% 1/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	3.7% 1/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	9.1% 1/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.9% 1/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	4.2% 2/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Psychiatric disorders Depersonalisation/Derealisation Disorder	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	4.9% 2/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	6.2% 3/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Psychiatric disorders Dissociation	34.1% 14/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	24.4% 10/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	55.0% 22/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	8.8% 7/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	64.6% 31/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Renal and urinary disorders Albuminuria	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	9.1% 1/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.9% 1/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.1% 1/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	1.2% 1/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	7.7% 1/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.1% 1/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.4% 1/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.0% 2/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.5% 2/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	2.1% 1/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Respiratory, thoracic and mediastinal disorders Rhinitis Allergic	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	7.7% 1/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	3.7% 1/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
Skin and subcutaneous tissue disorders Night Sweats	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/41 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/40 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/80 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/29 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/23 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/53 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/13 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/11 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	5.9% 1/17 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/27 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.	0.00% 0/48 • Up to 42 weeks There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.

Additional Information

Global Medical Head

Janssen Pharmaceutical K.K., Japan

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER