Trial Outcomes & Findings for A Dose-finding and Confirmatory Trial of OPC-6535 in Patients With Active Crohn's Disease (NCT NCT00989573)

Last Updated: 2021-04-06

Results Overview

Definition of clinical improvement: Total Crohn's Disease Activity Index (CDAI) score improved by at least 70 points from the baseline score or to below 150 (CDAI \< 150: remission, CDAI \> 450: severe disease)

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

191 participants

Primary outcome timeframe

Week 8

Results posted on

2021-04-06

Participant Flow

Participant milestones

Participant milestones
Measure	OPC-6535 25 mg Oral administration of OPC-6535 25 mg once daily for 8 weeks (started from 12.5 mg for the first week and the dose was titrated to 25 mg from the second week)	OPC-6535 50 mg Oral administration of OPC-6535 50mg once daily for 8 weeks (started from 12.5 mg for the first week and the dose was titrated to 25 mg from the second week, with further titration to 50 mg from the third week)	Placebo Oral administration of placebo once daily for 8 weeks
Overall Study STARTED	65	63	63
Overall Study COMPLETED	52	41	55
Overall Study NOT COMPLETED	13	22	8

Reasons for withdrawal

Reasons for withdrawal
Measure	OPC-6535 25 mg Oral administration of OPC-6535 25 mg once daily for 8 weeks (started from 12.5 mg for the first week and the dose was titrated to 25 mg from the second week)	OPC-6535 50 mg Oral administration of OPC-6535 50mg once daily for 8 weeks (started from 12.5 mg for the first week and the dose was titrated to 25 mg from the second week, with further titration to 50 mg from the third week)	Placebo Oral administration of placebo once daily for 8 weeks
Overall Study Adverse Event	8	12	4
Overall Study Physician Decision	0	2	0
Overall Study Protocol Violation	1	1	1
Overall Study Withdrawal by Subject	4	7	3

Baseline Characteristics

A Dose-finding and Confirmatory Trial of OPC-6535 in Patients With Active Crohn's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OPC-6535 25 mg n=64 Participants Oral administration of OPC-6535 25 mg once daily for 8 weeks (started from 12.5 mg for the first week and the dose was titrated to 25 mg from the second week)	OPC-6535 50 mg n=63 Participants Oral administration of OPC-6535 50mg once daily for 8 weeks (started from 12.5 mg for the first week and the dose was titrated to 25 mg from the second week, with further titration to 50 mg from the third week)	Placebo n=61 Participants Oral administration of placebo once daily for 8 weeks	Total n=188 Participants Total of all reporting groups
Age, Continuous	32.8 years STANDARD_DEVIATION 10.2 • n=5 Participants	30.5 years STANDARD_DEVIATION 10.3 • n=7 Participants	32.2 years STANDARD_DEVIATION 9.5 • n=5 Participants	31.8 years STANDARD_DEVIATION 10.0 • n=4 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	10 Participants n=7 Participants	23 Participants n=5 Participants	53 Participants n=4 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	53 Participants n=7 Participants	38 Participants n=5 Participants	135 Participants n=4 Participants
Region of Enrollment South Korea	24 Participants n=5 Participants	22 Participants n=7 Participants	23 Participants n=5 Participants	69 Participants n=4 Participants
Region of Enrollment Japan	40 Participants n=5 Participants	41 Participants n=7 Participants	38 Participants n=5 Participants	119 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 8

Population: Full analysis set comprised all subjects who received at least one dose of IMP and for whom postdosing efficacy data were obtained.

Outcome measures

Outcome measures
Measure	OPC-6535 25 mg n=64 Participants Oral administration of OPC-6535 25 mg once daily for 8 weeks (started from 12.5 mg for the first week and the dose was titrated to 25 mg from the second week)	OPC-6535 50 mg n=62 Participants Oral administration of OPC-6535 50mg once daily for 8 weeks (started from 12.5 mg for the first week and the dose was titrated to 25 mg from the second week, with further titration to 50 mg from the third week)	Placebo n=61 Participants Oral administration of placebo once daily for 8 weeks
Clinical Improvement Rate (Number of Subjects Showing Clinical Improvement / Number of Subjects Evaluated × 100) After 8 Weeks of IMP Administration	31.3 percentage of participants Interval 20.2 to 44.1	21.0 percentage of participants Interval 11.7 to 33.2	29.5 percentage of participants Interval 18.5 to 42.6

SECONDARY outcome

Timeframe: Week 4

Population: Full analysis set comprised all subjects who received at least one dose of IMP and for whom postdosing efficacy data were obtained.

Definition of clinical improvement: CDAI score improved by at least 70 points from the baseline score or to below 150 (CDAI \< 150: remission, CDAI \> 450: severe disease)

Outcome measures

Outcome measures
Measure	OPC-6535 25 mg n=63 Participants Oral administration of OPC-6535 25 mg once daily for 8 weeks (started from 12.5 mg for the first week and the dose was titrated to 25 mg from the second week)	OPC-6535 50 mg n=62 Participants Oral administration of OPC-6535 50mg once daily for 8 weeks (started from 12.5 mg for the first week and the dose was titrated to 25 mg from the second week, with further titration to 50 mg from the third week)	Placebo n=60 Participants Oral administration of placebo once daily for 8 weeks
Clinical Improvement Rate After 4 Weeks of IMP Administration	30.2 percentage of participants Interval 19.2 to 43.0	16.1 percentage of participants Interval 8.0 to 27.7	28.3 percentage of participants Interval 17.5 to 41.4

SECONDARY outcome

Timeframe: Weeks 4 and 8

Population: Full analysis set comprised all subjects who received at least one dose of IMP and for whom postdosing efficacy data were obtained.

Definition of remission: Total CDAI score improved to below 150

Outcome measures

Outcome measures
Measure	OPC-6535 25 mg n=64 Participants Oral administration of OPC-6535 25 mg once daily for 8 weeks (started from 12.5 mg for the first week and the dose was titrated to 25 mg from the second week)	OPC-6535 50 mg n=63 Participants Oral administration of OPC-6535 50mg once daily for 8 weeks (started from 12.5 mg for the first week and the dose was titrated to 25 mg from the second week, with further titration to 50 mg from the third week)	Placebo n=61 Participants Oral administration of placebo once daily for 8 weeks
Remission Rate (Number of Subjects Showing Remission / Number of Subjects Evaluated x 100) After 4 and 8 Weeks of IMP Administration Week 4	15.9 percentage of participants Interval 7.9 to 27.3	6.5 percentage of participants Interval 1.8 to 15.7	10.0 percentage of participants Interval 3.8 to 20.5
Remission Rate (Number of Subjects Showing Remission / Number of Subjects Evaluated x 100) After 4 and 8 Weeks of IMP Administration Week 8	20.3 percentage of participants Interval 11.3 to 32.2	11.3 percentage of participants Interval 4.7 to 21.9	18.0 percentage of participants Interval 9.4 to 30.0

SECONDARY outcome

Timeframe: Baseline, Weeks 4 and 8

Population: Full analysis set comprised all subjects who received at least one dose of IMP and for whom postdosing efficacy data were obtained.

Outcome measures

Outcome measures
Measure	OPC-6535 25 mg n=64 Participants Oral administration of OPC-6535 25 mg once daily for 8 weeks (started from 12.5 mg for the first week and the dose was titrated to 25 mg from the second week)	OPC-6535 50 mg n=63 Participants Oral administration of OPC-6535 50mg once daily for 8 weeks (started from 12.5 mg for the first week and the dose was titrated to 25 mg from the second week, with further titration to 50 mg from the third week)	Placebo n=61 Participants Oral administration of placebo once daily for 8 weeks
Mean Change From Baseline in C-reactive Protein (CRP) Level After 4 and 8 Weeks of IMP Administration Week 4	-0.19 mg/dL Standard Deviation 1.25	-0.16 mg/dL Standard Deviation 2.35	0.24 mg/dL Standard Deviation 1.58
Mean Change From Baseline in C-reactive Protein (CRP) Level After 4 and 8 Weeks of IMP Administration Week 8	-0.03 mg/dL Standard Deviation 1.92	-0.36 mg/dL Standard Deviation 2.19	0.34 mg/dL Standard Deviation 1.54

Adverse Events

OPC-6535 25 mg

Serious events: 8 serious events

Other events: 39 other events

Deaths: 0 deaths

OPC-6535 50 mg

Serious events: 10 serious events

Other events: 35 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	OPC-6535 25 mg n=65 participants at risk Oral administration of OPC-6535 25 mg once daily for 8 weeks (started from 12.5 mg for the first week and the dose was titrated to 25 mg from the second week)	OPC-6535 50 mg n=63 participants at risk Oral administration of OPC-6535 50mg once daily for 8 weeks (started from 12.5 mg for the first week and the dose was titrated to 25 mg from the second week, with further titration to 50 mg from the third week)	Placebo n=63 participants at risk Oral administration of placebo once daily for 8 weeks
Metabolism and nutrition disorders Hypophagia	1.5% 1/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Psychiatric disorders Schizophrenia	1.5% 1/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Gastrointestinal disorders Abdominal mass	0.00% 0/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	1.6% 1/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Gastrointestinal disorders Abdominal pain	1.5% 1/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Gastrointestinal disorders Crohn's disease	9.2% 6/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	7.9% 5/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	4.8% 3/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Gastrointestinal disorders Diarrhoea	0.00% 0/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	1.6% 1/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	1.6% 1/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	1.6% 1/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
General disorders Pyrexia	0.00% 0/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	1.6% 1/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Infections and infestations Abscess intestinal	0.00% 0/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	1.6% 1/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Infections and infestations Pulmonary tuberculosis	0.00% 0/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	1.6% 1/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Infections and infestations Tuberculosis gastrointestinal	0.00% 0/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	1.6% 1/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Infections and infestations Pulmonary tuberculoma	0.00% 0/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	1.6% 1/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.

Other adverse events

Additional Information

Director of Clinical Trials

Otsuka Pharmaceutical Co., LTD.

Phone: +81-3-6361-7366

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	OPC-6535 25 mg n=65 participants at risk Oral administration of OPC-6535 25 mg once daily for 8 weeks (started from 12.5 mg for the first week and the dose was titrated to 25 mg from the second week)	OPC-6535 50 mg n=63 participants at risk Oral administration of OPC-6535 50mg once daily for 8 weeks (started from 12.5 mg for the first week and the dose was titrated to 25 mg from the second week, with further titration to 50 mg from the third week)	Placebo n=63 participants at risk Oral administration of placebo once daily for 8 weeks
Blood and lymphatic system disorders Anaemia	3.1% 2/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	1.6% 1/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Cardiac disorders Palpitations	1.5% 1/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	3.2% 2/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Cardiac disorders Abdominal pain	6.2% 4/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	1.6% 1/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	1.6% 1/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Cardiac disorders Abdominal pain upper	1.5% 1/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	4.8% 3/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Cardiac disorders Crohn's disease	6.2% 4/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	7.9% 5/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	11.1% 7/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Cardiac disorders Dental caries	1.5% 1/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	3.2% 2/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Cardiac disorders Nausea	13.8% 9/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	15.9% 10/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	4.8% 3/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Cardiac disorders Stomatitis	0.00% 0/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	3.2% 2/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	3.2% 2/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Cardiac disorders Vomiting	3.1% 2/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	4.8% 3/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	3.2% 2/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
General disorders Malaise	4.6% 3/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	1.6% 1/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	1.6% 1/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
General disorders Pyrexia	3.1% 2/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	3.2% 2/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Infections and infestations Influenza	3.1% 2/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	1.6% 1/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Infections and infestations Nasopharyngitis	6.2% 4/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	4.8% 3/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	11.1% 7/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Infections and infestations Parotitis	0.00% 0/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	3.2% 2/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Investigations Blood triglycerides increased	3.1% 2/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	1.6% 1/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Investigations Blood urine present	4.6% 3/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	4.8% 3/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	1.6% 1/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	3.2% 2/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	1.6% 1/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Musculoskeletal and connective tissue disorders Arthralgia	3.1% 2/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Nervous system disorders Headache	13.8% 9/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	12.7% 8/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	6.3% 4/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Psychiatric disorders Insomnia	1.5% 1/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	3.2% 2/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	0.00% 0/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.
Skin and subcutaneous tissue disorders Rash	0.00% 0/65 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	3.2% 2/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.	1.6% 1/63 • From the start of IMP administration up to 3 weeks after the end of the trial Adverse events (AEs) occurring after IMP administration were included in assessment of AEs. The safety analysis population comprised subjects who received at least one dose of IMP.