Trial Outcomes & Findings for A Safety and Effectiveness Study of Golimumab in Japanese Patients With Moderately to Severely Active Ulcerative Colitis. (NCT NCT01863771)

Last Updated: 2017-04-05

Results Overview

Clinical response was defined as a decrease from Induction-Week 0 in the Mayo score by greater than or equal to (\>=) 30 percent and \>=3 points, with a decrease in the rectal bleeding subscore of \>= 1 or a rectal bleeding subscore of 0 or 1. The Mayo score is the primary tool for assessing ulcerative colitis activity. The Mayo score consists of 4 subscores (stool frequency, rectal bleeding, findings of endoscopy, and physician's global assessment) which range from 0 to 3. The Mayo score is calculated as the sum of these 4 subscores and can range between 0 and 12. A score of 3 to 5 points indicates mildly active disease; a score of 6 to 10 indicates moderately active disease; and a score of 11 to 12 indicates severe disease.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

144 participants

Primary outcome timeframe

Up to Week 54

Results posted on

2017-04-05

Participant Flow

Participant milestones

Participant milestones
Measure	Group1: Golimumab [Induction] Participants received golimumab 200 milligram (mg) once at Week 0 and golimumab 100 mg once at Week 2 subcutaneously (SC).	Group 2: Golimumab 100 mg [Maintenance] Participants who responded to golimumab induction treatment received golimumab 100 mg SC every 4 weeks (q4w) through Week 52.	Group 3: Placebo [Maintenance] Participants who responded to golimumab induction treatment received placebo SC every 4 weeks (q4w) through Week 52.	Group 4: Golimumab 100 mg [Maintenance] Participants who not responded to golimumab induction dosing received golimumab 100 mg SC once at Week 0 and once at Week 4, and based on clinical response every 4 weeks through Week 52.
Induction Phase STARTED	144	0	0	0
Induction Phase COMPLETED	123	0	0	0
Induction Phase NOT COMPLETED	21	0	0	0
Maintenance Phase STARTED	0	32	31	60
Maintenance Phase COMPLETED	0	27	19	17
Maintenance Phase NOT COMPLETED	0	5	12	43

Reasons for withdrawal

Reasons for withdrawal
Measure	Group1: Golimumab [Induction] Participants received golimumab 200 milligram (mg) once at Week 0 and golimumab 100 mg once at Week 2 subcutaneously (SC).	Group 2: Golimumab 100 mg [Maintenance] Participants who responded to golimumab induction treatment received golimumab 100 mg SC every 4 weeks (q4w) through Week 52.	Group 3: Placebo [Maintenance] Participants who responded to golimumab induction treatment received placebo SC every 4 weeks (q4w) through Week 52.	Group 4: Golimumab 100 mg [Maintenance] Participants who not responded to golimumab induction dosing received golimumab 100 mg SC once at Week 0 and once at Week 4, and based on clinical response every 4 weeks through Week 52.
Induction Phase Adverse Event	9	0	0	0
Induction Phase Lack of Efficacy	10	0	0	0
Induction Phase Withdrawal by Subject	2	0	0	0
Maintenance Phase Adverse Event	0	0	1	1
Maintenance Phase Lack of Efficacy	0	3	7	38
Maintenance Phase Physician Decision	0	0	2	1
Maintenance Phase Pregnancy	0	1	0	0
Maintenance Phase Withdrawal by Subject	0	1	2	3

Baseline Characteristics

A Safety and Effectiveness Study of Golimumab in Japanese Patients With Moderately to Severely Active Ulcerative Colitis.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=144 Participants Participants who received golimumab 200 milligram (mg) once at Week 0 and golimumab 100 mg once at Week 2 subcutaneously (SC) in the induction phase.
Age, Continuous	42.4 years STANDARD_DEVIATION 14.74 • n=5 Participants
Sex: Female, Male Female	46 Participants n=5 Participants
Sex: Female, Male Male	98 Participants n=5 Participants
Region of Enrollment Japan	144 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Week 54

Population: Efficacy full analysis set for maintenance phase included all participants who responded to golimumab induction treatment and subsequently randomized at Week 0 in maintenance phase. Data for this outcome was not planned to be analyzed for participants who had not responded to golimumab induction dosing, as pre-specified in protocol.

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants Participants who responded to golimumab induction treatment received placebo subcutaneously (SC) every 4 weeks (q4w) through Week 52 in the maintenance phase.	Golimumab n=32 Participants Participants received golimumab 200 mg (once at Week 0) and golimumab 100 mg (once at Week 2) SC in induction phase. Participants who responded to golimumab induction treatment received golimumab 100 mg SC, q4w through Week 52 and participants who not responded to golimumab induction treatment received golimumab 100 mg SC at Weeks 0 and 4, and based on clinical response every 4 weeks through Week 52 in maintenance phase.
Number of Participants Who Achieved Clinical Response Through Maintenance-Week 54 Measured Using the Mayo Score	6 participants Interval 5.4 to 33.3	18 participants Interval 39.1 to 73.4

SECONDARY outcome

Timeframe: Weeks 30 and 54

Clinical remission (as measured by the Mayo score) was defined as a Mayo score of less than or equal to (\<=) 2 points, with no individual sub-score greater than (\>) 1.

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants Participants who responded to golimumab induction treatment received placebo subcutaneously (SC) every 4 weeks (q4w) through Week 52 in the maintenance phase.	Golimumab n=32 Participants Participants received golimumab 200 mg (once at Week 0) and golimumab 100 mg (once at Week 2) SC in induction phase. Participants who responded to golimumab induction treatment received golimumab 100 mg SC, q4w through Week 52 and participants who not responded to golimumab induction treatment received golimumab 100 mg SC at Weeks 0 and 4, and based on clinical response every 4 weeks through Week 52 in maintenance phase.
Number of Participants Who Achieved Clinical Remission at Both Maintenance-Week 30 and Week 54	2 participants	16 participants

SECONDARY outcome

Timeframe: Weeks 30 and 54

Mucosal healing is defined as an endoscopy subscore of 0 or 1, where 0 indicates normal or inactive disease and 1 indicates mild disease (erythema, decreased vascular pattern, mild friability). Endoscopy subscore is one of the 4 subscores of the Mayo score.

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants Participants who responded to golimumab induction treatment received placebo subcutaneously (SC) every 4 weeks (q4w) through Week 52 in the maintenance phase.	Golimumab n=32 Participants Participants received golimumab 200 mg (once at Week 0) and golimumab 100 mg (once at Week 2) SC in induction phase. Participants who responded to golimumab induction treatment received golimumab 100 mg SC, q4w through Week 52 and participants who not responded to golimumab induction treatment received golimumab 100 mg SC at Weeks 0 and 4, and based on clinical response every 4 weeks through Week 52 in maintenance phase.
Number of Participants With Mucosal Healing at Both Maintenance-Week 30 and Week 54	5 participants	19 participants

Adverse Events

Group1: Golimumab [Induction]

Serious events: 5 serious events

Other events: 36 other events

Deaths: 0 deaths

Group 2: Golimumab 100 mg [Maintenance]

Serious events: 1 serious events

Other events: 26 other events

Deaths: 0 deaths

Group 3: Placebo [Maintenance]

Serious events: 4 serious events

Other events: 15 other events

Deaths: 0 deaths

Group 4: Golimumab 100 mg [Maintenance]

Serious events: 6 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Group1: Golimumab [Induction] n=144 participants at risk Participants received golimumab 200 milligram (mg) once at Week 0 and golimumab 100 mg once at Week 2 subcutaneously (SC).	Group 2: Golimumab 100 mg [Maintenance] n=32 participants at risk Participants who responded to golimumab induction treatment received golimumab 100 mg SC every 4 weeks (q4w) through Week 52.	Group 3: Placebo [Maintenance] n=31 participants at risk Participants who responded to golimumab induction treatment received placebo SC every 4 weeks (q4w) through Week 52.	Group 4: Golimumab 100 mg [Maintenance] n=60 participants at risk Participants who not responded to golimumab induction dosing received golimumab 100 mg SC once at Week 0 and once at Week 4, and based on clinical response every 4 week through Week 52.
Gastrointestinal disorders Colitis Ulcerative	2.8% 4/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	3.2% 1/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	8.3% 5/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Infections and infestations Cytomegalovirus Colitis	0.69% 1/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Infections and infestations Herpes Zoster	0.00% 0/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	3.3% 2/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Infections and infestations Pharyngitis	0.00% 0/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	1.7% 1/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Injury, poisoning and procedural complications Hand Fracture	0.00% 0/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	3.2% 1/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Injury, poisoning and procedural complications Joint Dislocation	0.00% 0/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	3.2% 1/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Nervous system disorders Cerebral Infarction	0.00% 0/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	3.2% 1/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Vascular disorders Takayasu's Arteritis	0.00% 0/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	3.1% 1/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.

Other adverse events

Additional Information

Senior Director Clinical Development

Janssen Pharmaceutical K.K.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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 in writing, such publication will be withheld for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER

Measure	Group1: Golimumab [Induction] n=144 participants at risk Participants received golimumab 200 milligram (mg) once at Week 0 and golimumab 100 mg once at Week 2 subcutaneously (SC).	Group 2: Golimumab 100 mg [Maintenance] n=32 participants at risk Participants who responded to golimumab induction treatment received golimumab 100 mg SC every 4 weeks (q4w) through Week 52.	Group 3: Placebo [Maintenance] n=31 participants at risk Participants who responded to golimumab induction treatment received placebo SC every 4 weeks (q4w) through Week 52.	Group 4: Golimumab 100 mg [Maintenance] n=60 participants at risk Participants who not responded to golimumab induction dosing received golimumab 100 mg SC once at Week 0 and once at Week 4, and based on clinical response every 4 week through Week 52.
Blood and lymphatic system disorders Anaemia	0.69% 1/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	5.0% 3/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Gastrointestinal disorders Abdominal Pain Upper	0.00% 0/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	6.2% 2/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	3.2% 1/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	1.7% 1/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Gastrointestinal disorders Colitis Ulcerative	4.9% 7/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	6.5% 2/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	6.7% 4/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
General disorders Injection Site Erythema	3.5% 5/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	15.6% 5/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	1.7% 1/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
General disorders Injection Site Pain	0.00% 0/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	6.2% 2/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
General disorders Pyrexia	1.4% 2/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	6.2% 2/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	3.3% 2/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Infections and infestations Gastroenteritis	0.00% 0/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	5.0% 3/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Infections and infestations Herpes Zoster	0.69% 1/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	5.0% 3/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Infections and infestations Influenza	0.00% 0/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	12.5% 4/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	3.2% 1/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	5.0% 3/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Infections and infestations Nasopharyngitis	11.8% 17/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	53.1% 17/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	22.6% 7/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	23.3% 14/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Infections and infestations Oral Herpes	0.00% 0/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	3.1% 1/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	9.7% 3/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	3.3% 2/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Investigations White Blood Cell Count Decreased	0.69% 1/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	6.2% 2/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Musculoskeletal and connective tissue disorders Back Pain	0.69% 1/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	6.2% 2/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	3.2% 1/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	3.3% 2/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Nervous system disorders Headache	2.1% 3/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	3.1% 1/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	6.5% 2/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	1.7% 1/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Psychiatric disorders Insomnia	0.00% 0/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	3.2% 1/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	5.0% 3/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Respiratory, thoracic and mediastinal disorders Cough	0.69% 1/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	6.2% 2/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	3.2% 1/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	3.3% 2/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Respiratory, thoracic and mediastinal disorders Upper Respiratory Tract Inflammation	0.00% 0/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	3.1% 1/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	6.7% 4/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/144 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	6.2% 2/32 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	6.5% 2/31 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.	0.00% 0/60 Safety data were analyzed separately for all treated participants in the induction phase and randomized and non-randomized participants in the maintenance phase. Participants were analyzed according to the actual treatment they received.