Trial Outcomes & Findings for A Study of Golimumab in Participants With Active Psoriatic Arthritis (NCT NCT02181673)

Last Updated: 2017-12-21

Results Overview

The ACR 20 response is defined as greater than or equal to (\>=) 20 percent (%) improvement from baseline in both swollen joint count (66 joints) and tender joint count (68 joints) and \>=20% improvement from baseline in at least 3 of the following 5 assessments: Patient's assessment of pain (on a 0 to 10 centimeter \[cm\] scale), Patient's Global Assessment of Disease Activity (on a 0 to 10 cm scale), Physician's Global Assessment of Disease Activity (on a 0 to 10 cm scale), Patient's assessment of physical function as measured by Disability Index of the Health Assessment Questionnaire (HAQ-DI) and measurement of a blood test called C-reactive protein (CRP).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

480 participants

Primary outcome timeframe

Week 14

Results posted on

2017-12-21

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo (Week 0-24) Participants received intravenous infusions of placebo at Weeks 0, 4, 12 and 20.	Placebo Then Golimumab 2 mg/kg (Week 24-60) Participants who received placebo up to Week 20 were then crossed over at Week 24 to receive intravenous infusions of golimumab 2 milligram per kilogram (mg/kg) at Week 24, 28 and every 8 weeks thereafter up to Week 52.	Golimumab 2 mg/kg (Week 0-60) Participants were randomized to receive intravenous infusions of golimumab 2 mg/kg at Weeks 0, 4 and every 8 weeks thereafter up to Week 52. At Week 24, participants received a placebo intravenous infusion to maintain the blind.
Up to Week 24 STARTED	239	0	241
Up to Week 24 Treated	239	0	240
Up to Week 24 COMPLETED	222	0	230
Up to Week 24 NOT COMPLETED	17	0	11
Week 24-Week 60 STARTED	0	222	230
Week 24-Week 60 Treated	0	220	230
Week 24-Week 60 COMPLETED	0	214	213
Week 24-Week 60 NOT COMPLETED	0	8	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo (Week 0-24) Participants received intravenous infusions of placebo at Weeks 0, 4, 12 and 20.	Placebo Then Golimumab 2 mg/kg (Week 24-60) Participants who received placebo up to Week 20 were then crossed over at Week 24 to receive intravenous infusions of golimumab 2 milligram per kilogram (mg/kg) at Week 24, 28 and every 8 weeks thereafter up to Week 52.	Golimumab 2 mg/kg (Week 0-60) Participants were randomized to receive intravenous infusions of golimumab 2 mg/kg at Weeks 0, 4 and every 8 weeks thereafter up to Week 52. At Week 24, participants received a placebo intravenous infusion to maintain the blind.
Up to Week 24 Adverse Event	2	0	3
Up to Week 24 Death	1	0	0
Up to Week 24 Lack of Efficacy	1	0	0
Up to Week 24 Lost to Follow-up	1	0	0
Up to Week 24 Physician Decision	0	0	3
Up to Week 24 Withdrawal by Subject	10	0	1
Up to Week 24 Other	2	0	3
Up to Week 24 Randomized not Treated	0	0	1
Week 24-Week 60 Adverse Event	0	4	10
Week 24-Week 60 Other	0	2	1
Week 24-Week 60 Withdrawal by Subject	0	2	2
Week 24-Week 60 Pregnancy	0	0	1
Week 24-Week 60 Lack of Efficacy	0	0	1
Week 24-Week 60 Lost to Follow-up	0	0	1
Week 24-Week 60 Physician Decision	0	0	1

Baseline Characteristics

A Study of Golimumab in Participants With Active Psoriatic Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo (Week 0-24) n=239 Participants Participants received intravenous infusions of placebo at Weeks 0, 4, 12 and 20.	Golimumab 2 mg/kg n=241 Participants Participants were randomized to receive intravenous infusions of golimumab 2 mg/kg at Weeks 0, 4 and every 8 weeks thereafter up to Week 52. At Week 24, participants received a placebo intravenous infusion to maintain the blind.	Total n=480 Participants Total of all reporting groups
Age, Categorical <=18 years	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	216 Participants n=5 Participants	228 Participants n=7 Participants	444 Participants n=5 Participants
Age, Categorical >=65 years	21 Participants n=5 Participants	13 Participants n=7 Participants	34 Participants n=5 Participants
Age, Continuous	46.7 years STANDARD_DEVIATION 12.53 • n=5 Participants	45.7 years STANDARD_DEVIATION 11.25 • n=7 Participants	46.2 years STANDARD_DEVIATION 11.9 • n=5 Participants
Sex: Female, Male Female	118 Participants n=5 Participants	113 Participants n=7 Participants	231 Participants n=5 Participants
Sex: Female, Male Male	121 Participants n=5 Participants	128 Participants n=7 Participants	249 Participants n=5 Participants
Region of Enrollment Belarus	14 Participants n=5 Participants	8 Participants n=7 Participants	22 Participants n=5 Participants
Region of Enrollment Canada	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Germany	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Hungary	13 Participants n=5 Participants	9 Participants n=7 Participants	22 Participants n=5 Participants
Region of Enrollment Lithuania	13 Participants n=5 Participants	17 Participants n=7 Participants	30 Participants n=5 Participants
Region of Enrollment Poland	43 Participants n=5 Participants	34 Participants n=7 Participants	77 Participants n=5 Participants
Region of Enrollment Romania	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Russian Federation	79 Participants n=5 Participants	74 Participants n=7 Participants	153 Participants n=5 Participants
Region of Enrollment Spain	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Ukraine	61 Participants n=5 Participants	86 Participants n=7 Participants	147 Participants n=5 Participants
Region of Enrollment United States	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 14

Population: The full analysis set (FAS) included all participants who were randomized.

Outcome measures

Outcome measures
Measure	Placebo n=239 Participants Participants received intravenous infusions of placebo at Weeks 0, 4, 12 and 20.	Golimumab n=241 Participants Participants were randomized to receive intravenous infusions of golimumab 2 mg/kg at Weeks 0, 4 and thereafter every 8 weeks up to Week 52. At Week 24, participants received a placebo infusion to maintain the blind.
Percentage of Participants Who Achieved an American College of Rheumatology (ACR) 20 Response at Week 14	21.8 Percentage of Participants	75.1 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline and Week 14

Population: The full analysis set (FAS) included all participants who were randomized. Here "N" (number of participants analyzed) signifies the number of participants who were evaluable for this outcome measure.

The Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and activities of daily living). Responses in each functional area are scored from 0 to 3 (0=no difficulty and 3=inability to perform a task in that area). Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Participants received intravenous infusions of placebo at Weeks 0, 4, 12 and 20.	Golimumab n=233 Participants Participants were randomized to receive intravenous infusions of golimumab 2 mg/kg at Weeks 0, 4 and thereafter every 8 weeks up to Week 52. At Week 24, participants received a placebo infusion to maintain the blind.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 14	-0.12 units on a scale Standard Deviation 0.466	-0.60 units on a scale Standard Deviation 0.530

SECONDARY outcome

Timeframe: Week 14

Population: The full analysis set (FAS) included all participants who were randomized.

The ACR 50 response is defined as: greater than or equal to (\>=) 50 percent (%) improvement from baseline in both swollen joint count (66 joints) and tender joint count (68 joints) and \>=50% improvement from baseline in at least 3 of the following 5 assessments: Patient's assessment of pain (on a 0 to 10 cm scale), Patient's Global Assessment of Disease Activity (on a 0 to 10 cm scale), Physician's Global Assessment of Disease Activity (on a 0 to 10 cm scale), Patient's assessment of physical function as measured by Disability Index of the Health Assessment Questionnaire (HAQ-DI) and measurement of a blood test called C-reactive protein (CRP).

Outcome measures

Outcome measures
Measure	Placebo n=239 Participants Participants received intravenous infusions of placebo at Weeks 0, 4, 12 and 20.	Golimumab n=241 Participants Participants were randomized to receive intravenous infusions of golimumab 2 mg/kg at Weeks 0, 4 and thereafter every 8 weeks up to Week 52. At Week 24, participants received a placebo infusion to maintain the blind.
Percentage of Participants Who Achieved an ACR 50 Response at Week 14	6.3 Percentage of Participants	43.6 Percentage of Participants

SECONDARY outcome

Timeframe: Week 14

Population: The analysis set included randomized participants with greater than or equal to (\>=) 3 percent (%) body surface area (BSA) Psoriasis Skin Involvement at Baseline.

The PASI is a system used for assessing and grading the severity of psoriatic lesions. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 75 response represents participants who achieved at least a 75 percent improvement from baseline in the PASI score.

Outcome measures

Outcome measures
Measure	Placebo n=198 Participants Participants received intravenous infusions of placebo at Weeks 0, 4, 12 and 20.	Golimumab n=196 Participants Participants were randomized to receive intravenous infusions of golimumab 2 mg/kg at Weeks 0, 4 and thereafter every 8 weeks up to Week 52. At Week 24, participants received a placebo infusion to maintain the blind.
Percentage of Participants Who Achieved Psoriatic Area and Severity Index (PASI) 75 Response at Week 14	13.6 Percentage of participants	59.2 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: FAS for structural damage endpoints (FAS-SD) defined as participants in the FAS who were treated and had a non-missing baseline total modified vdH-S score for the analysis.

The modified vdH-S score is a radiographic evaluation of hand and feet erosions and joint space narrowing (JSN) for 20 joints per hand and 6 joints per foot with a total score ranging from 0 (best) to 528 (worst = worst possible erosion score of 320 + worst possible JSN score of 208). Higher score and positive score changes indicate more radiographic damage and radiographic progression, respectively.

Outcome measures

Outcome measures
Measure	Placebo n=237 Participants Participants received intravenous infusions of placebo at Weeks 0, 4, 12 and 20.	Golimumab n=237 Participants Participants were randomized to receive intravenous infusions of golimumab 2 mg/kg at Weeks 0, 4 and thereafter every 8 weeks up to Week 52. At Week 24, participants received a placebo infusion to maintain the blind.
Change From Baseline in Total Modified Van Der Heijde-Sharp (vdH-S) Score at Week 24	1.95 units on a scale Standard Error 0.264	-0.36 units on a scale Standard Error 0.144

SECONDARY outcome

Timeframe: Baseline and Week 14

Population: Population included all randomized participants with Enthesitis at Baseline. Here "N" (number of participants analyzed) signifies the number of participants who were evaluable for this outcome measure.

Enthesitis will be assessed using the Leeds Enthesitis Index (LEI). The LEI was developed to assess enthesitis in participants with PsA, and evaluates the presence (score of 1) or absence of pain (score of 0) by applying local pressure to Lateral elbow epicondyle, left and right, Medial femoral condyle, left and right, and Achilles tendon insertion, left and right. LEI scores ranging from 0 (0 sites with tenderness) to 6 (worst possible score; 6 sites with tenderness).

Outcome measures

Outcome measures
Measure	Placebo n=173 Participants Participants received intravenous infusions of placebo at Weeks 0, 4, 12 and 20.	Golimumab n=182 Participants Participants were randomized to receive intravenous infusions of golimumab 2 mg/kg at Weeks 0, 4 and thereafter every 8 weeks up to Week 52. At Week 24, participants received a placebo infusion to maintain the blind.
Change From Baseline in Leeds Enthesitis Index (LEI) at Week 14 in Participants With Enthesitis at Baseline	-0.8 units on a scale Standard Deviation 1.98	-1.8 units on a scale Standard Deviation 1.75

SECONDARY outcome

Timeframe: Baseline and Week 14

Population: Population included all Randomized participants With Dactylitis (Score \>0) at Baseline. Here "N" (number of participants analyzed) signifies the number of participants who were evaluable for this outcome measure.

Dactylitis is characterized by swelling of the entire finger or toe. The severity of dactylitis is scored on a scale of 0-3, where 0=tenderness and 3=extreme tenderness in each digit of the hands and feet. The range of total dactylitis scores for a participant is 0-60. Higher score indicates greater degree of tenderness.

Outcome measures

Outcome measures
Measure	Placebo n=115 Participants Participants received intravenous infusions of placebo at Weeks 0, 4, 12 and 20.	Golimumab n=130 Participants Participants were randomized to receive intravenous infusions of golimumab 2 mg/kg at Weeks 0, 4 and thereafter every 8 weeks up to Week 52. At Week 24, participants received a placebo infusion to maintain the blind.
Change From Baseline in Dactylitis Scores at Week 14 in Participants With Dactylitis at Baseline	-2.8 units on a scale Standard Deviation 7.03	-7.8 units on a scale Standard Deviation 8.57

SECONDARY outcome

Timeframe: Baseline and Week 14

Population: The full analysis set (FAS) included all participants who were randomized. Here "N" (number of participants analyzed) signifies the number of participants evaluable for this outcome measure.

The SF-36 is a survey of participant health. It consists of 8 individual domains, which are weighted sums of the questions in their section. The 8 domains are: vitality (VT), physical functioning (PF), bodily pain (BP), general health (GH), Role-Physical (RP), Role-Emotional (RE), social functioning (SF) and mental health (MH). Each of these 8 scales (domains) is scored from 0 to 100 with higher scores indicating better health. Based on the scale scores, the summary physical component score (PCS) is derived. Scales contributing most to the scoring of the SF-36 PCS include the PF, RP, BP and GH. Other domains not noted contribute to the scoring but to a lesser degree. The scoring is derived based on an algorithm that has been developed in a software provided by the developer. The summary PCS score is also scaled from 0 to 100 with higher scores indicating better health.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Participants received intravenous infusions of placebo at Weeks 0, 4, 12 and 20.	Golimumab n=233 Participants Participants were randomized to receive intravenous infusions of golimumab 2 mg/kg at Weeks 0, 4 and thereafter every 8 weeks up to Week 52. At Week 24, participants received a placebo infusion to maintain the blind.
Change From Baseline in Short Form-36 Health Survey (SF-36) Physical Component Summary (PCS) at Week 14	2.69 units on a scale Standard Deviation 5.920	8.65 units on a scale Standard Deviation 7.602

SECONDARY outcome

Timeframe: Week 24

Population: The full analysis set (FAS) included all participants who were randomized.

The ACR 50 response is defined as greater than or equal to (\>=) 50 percent (%) improvement from baseline in both swollen joint count (66 joints) and tender joint count (68 joints) and \>=50% improvement from baseline in at least 3 of the following 5 assessments: Patient's assessment of pain (on a 0 to 10 centimeter \[cm\] scale), Patient's Global Assessment of Disease Activity (on a 0 to 10 cm scale), Physician's Global Assessment of Disease Activity (on a 0 to 10 cm scale), Patient's assessment of physical function as measured by Disability Index of the Health Assessment Questionnaire (HAQ-DI) and measurement of a blood test called C-reactive protein (CRP).

Outcome measures

Outcome measures
Measure	Placebo n=239 Participants Participants received intravenous infusions of placebo at Weeks 0, 4, 12 and 20.	Golimumab n=241 Participants Participants were randomized to receive intravenous infusions of golimumab 2 mg/kg at Weeks 0, 4 and thereafter every 8 weeks up to Week 52. At Week 24, participants received a placebo infusion to maintain the blind.
Percentage of Participants Who Achieved an American College of Rheumatology (ACR) 50 Response at Week 24	6.3 Percentage of participants	53.5 Percentage of participants

SECONDARY outcome

Timeframe: Week 14

Population: The full analysis set (FAS) included all participants who were randomized.

The ACR 70 response is defined as greater than or equal to (\>=) 70 percent (%) improvement from baseline in both swollen joint count (66 joints) and tender joint count (68 joints) and \>=70% improvement from baseline in at least 3 of the following 5 assessments: Patient's assessment of pain (on a 0 to 10 centimeter \[cm\] scale), Patient's Global Assessment of Disease Activity (on a 0 to 10 cm scale), Physician's Global Assessment of Disease Activity (on a 0 to 10 cm scale), Patient's assessment of physical function as measured by Disability Index of the Health Assessment Questionnaire (HAQ-DI) and measurement of a blood test called C-reactive protein (CRP).

Outcome measures

Outcome measures
Measure	Placebo n=239 Participants Participants received intravenous infusions of placebo at Weeks 0, 4, 12 and 20.	Golimumab n=241 Participants Participants were randomized to receive intravenous infusions of golimumab 2 mg/kg at Weeks 0, 4 and thereafter every 8 weeks up to Week 52. At Week 24, participants received a placebo infusion to maintain the blind.
Percentage of Participants Who Achieved an American College of Rheumatology (ACR) 70 Response at Week 14	2.1 Percentage of participants	24.5 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 14

The SF-36 is a survey of participant health. It consists of 8 individual domains, which are weighted sums of the questions in their section. The 8 domains are: vitality (VT), physical functioning (PF), bodily pain (BP), general health (GH), Role-Physical (RP), Role-Emotional (RE), social functioning (SF) and mental health (MH). Each of these 8 scales (domains) is scored from 0 to 100 with higher scores indicating better health. Based on the scale scores, the summary mental component score (MCS) is derived. Scales contributing most to the scoring of the SF-36 MCS include the VT, SF, RE and MH. Other domains not noted contribute to the scoring but to a lesser degree. The scoring is derived based on an algorithm that has been developed in a software provided by the developer. The summary MCS score is also scaled from 0 to 100 with higher scores indicating better health.

Outcome measures

Outcome measures
Measure	Placebo n=222 Participants Participants received intravenous infusions of placebo at Weeks 0, 4, 12 and 20.	Golimumab n=233 Participants Participants were randomized to receive intravenous infusions of golimumab 2 mg/kg at Weeks 0, 4 and thereafter every 8 weeks up to Week 52. At Week 24, participants received a placebo infusion to maintain the blind.
Change From Baseline in Short Form-36 Health Survey (SF)-36 Mental Component Summary (MCS) at Week 14	0.97 units on a scale Standard Deviation 7.644	5.33 units on a scale Standard Deviation 9.948

Adverse Events

Placebo (Week 0-24)

Serious events: 8 serious events

Other events: 19 other events

Deaths: 0 deaths

Placebo Then Golimumab 2 mg/kg (Week 24-60)

Serious events: 5 serious events

Other events: 25 other events

Deaths: 0 deaths

Golimumab 2 mg/kg (Week 0-60)

Serious events: 19 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo (Week 0-24) n=239 participants at risk Participants received intravenous infusions of placebo at Weeks 0, 4, 12 and 20.	Placebo Then Golimumab 2 mg/kg (Week 24-60) n=220 participants at risk Participants who received placebo up to Week 20 were then crossed over at Week 24 to receive intravenous infusions of golimumab 2 milligram per kilogram (mg/kg) at Week 24, 28 and every 8 weeks thereafter up to Week 52.	Golimumab 2 mg/kg (Week 0-60) n=240 participants at risk Participants were randomized to receive intravenous infusions of golimumab 2 mg/kg at Weeks 0, 4 and every 8 weeks thereafter up to Week 52. At Week 24, participants received a placebo intravenous infusion to maintain the blind.
Infections and infestations Nasopharyngitis	5.4% 13/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	4.1% 9/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	5.8% 14/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Investigations Alanine aminotransferase increased	2.1% 5/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	5.9% 13/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	10.4% 25/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Investigations Aspartate aminotransferase increased	2.1% 5/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	5.5% 12/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	7.9% 19/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.

Additional Information

Senior Director Clinical Development

Janssen Research & Development, LLC

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	Placebo (Week 0-24) n=239 participants at risk Participants received intravenous infusions of placebo at Weeks 0, 4, 12 and 20.	Placebo Then Golimumab 2 mg/kg (Week 24-60) n=220 participants at risk Participants who received placebo up to Week 20 were then crossed over at Week 24 to receive intravenous infusions of golimumab 2 milligram per kilogram (mg/kg) at Week 24, 28 and every 8 weeks thereafter up to Week 52.	Golimumab 2 mg/kg (Week 0-60) n=240 participants at risk Participants were randomized to receive intravenous infusions of golimumab 2 mg/kg at Weeks 0, 4 and every 8 weeks thereafter up to Week 52. At Week 24, participants received a placebo intravenous infusion to maintain the blind.
Cardiac disorders Cardiac failure acute	0.42% 1/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Cardiac disorders Myocardial ischaemia	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Eye disorders Cataract	0.42% 1/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Gastrointestinal disorders Oedematous pancreatitis	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Hepatobiliary disorders Drug-induced liver injury	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Hepatobiliary disorders Hepatitis acute	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Hepatobiliary disorders Hepatitis chronic active	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Infections and infestations Empyema	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.45% 1/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Infections and infestations Infected dermal cyst	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Infections and infestations Periodontitis	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.45% 1/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Infections and infestations Pneumonia	0.42% 1/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.45% 1/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.83% 2/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Infections and infestations Pulmonary tuberculosis	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.83% 2/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Infections and infestations Pyelonephritis acute	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Infections and infestations Urinary tract infection	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.45% 1/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Injury, poisoning and procedural complications Epidural haemorrhage	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Injury, poisoning and procedural complications Facial bones fracture	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Injury, poisoning and procedural complications Humerus fracture	0.42% 1/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Injury, poisoning and procedural complications Skull fracture	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Investigations Gene mutation identification test positive	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.45% 1/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Investigations Laboratory test abnormal	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.45% 1/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Investigations Liver function test abnormal	0.42% 1/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.45% 1/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma benign	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.42% 1/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal neoplasm	0.42% 1/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pleomorphic adenoma	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Nervous system disorders Cerebral haematoma	0.42% 1/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Nervous system disorders Headache	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Nervous system disorders Neuritis	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Nervous system disorders Paraesthesia	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Renal and urinary disorders Calculus urinary	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Renal and urinary disorders Renal failure	0.42% 1/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.42% 1/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Skin and subcutaneous tissue disorders Pustular psoriasis	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Vascular disorders Deep vein thrombosis	0.42% 1/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Vascular disorders Hypertension	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.
Vascular disorders Hypertensive crisis	0.00% 0/239 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.00% 0/220 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.	0.42% 1/240 • Up to 60 Weeks Safety Population included all participants who received at least 1 dose of study agent.