Trial Outcomes & Findings for Efficacy and Safety Study of Adalimumab in the Treatment of Hidradenitis Suppurativa (NCT NCT01468233)

NCT ID: NCT01468233

Last Updated: 2021-07-12

Results Overview

HiSCR was defined as at least a 50% reduction in abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count at Week 12 relative to Baseline. Data are presented for all participants and by baseline Hurley Stage (Stage 1: Abscess formation, single or multiple, without sinus tracts and scarring; Stage II: One or more widely separated recurrent abscesses with tract formation and scars. A participant with at least 1 anatomic region with Hurley Stage II disease and with no anatomic regions with Hurley Stage III disease was classified as Hurley Stage II; and Stage III: Multiple interconnected tracts and abscesses across the entire area, with diffuse or near diffuse involvement. A participant with at least 1 anatomic region with Hurley Stage III disease was classified as Hurley Stage III). Non-responder imputation (NRI): Participants with missing data were considered non-responders.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 326 participants
• Primary outcome timeframe: Baseline (Week 0) up to Week 12
• Results posted on: 2021-07-12

Participant Flow

Participants ≥ 18 years of age with HS for at least 1 year prior to Baseline and HS lesions present in at least 2 distinct anatomical areas (one of which must be at least Hurley Stage II or III) who had experienced inadequate response to ≥ 90 day treatment of oral antibiotics for HS were eligible for enrolment in the study.

Participant milestones

Measure	Placebo Placebo for 12 weeks	Adalimumab Every Week (EW) Adalimumab ew for 12 weeks (160 mg at Week 0; 80 mg at Week 2; and 40 mg ew from Week 4 to Week 12).	Placebo/Placebo Participants randomized to receive placebo in Period 1 received placebo every week from Week 12 to Week 35 in Period 2 (up to 24 weeks).	Adalimumab Every Week (EW)/Placebo Participants randomized to receive adalimumab ew in Period 1 were re-randomized to receive placebo ew from Week 12 to Week 35 in Period 2 (up to 24 weeks).	Adalimumab Every Week (EW)/ Adalimumab Every Other Week (EOW) Participants randomized to receive adalimumab ew in Period 1 were re-randomized to receive 40 mg adalimumab eow from Week 12 to Week 35 in Period 2; placebo injections were administered eow from Week 13 to Week 35 (up to 24 weeks).	Adalimumab Every Week (EW)/Adalimumab Every Week (EW) Participants randomized to receive adalimumab ew in Period 1 were re-randomized to receive 40 mg adalimumab ew from Week 12 to Week 35 in Period 2 (up to 24 weeks).
Treatment Period 1 STARTED	163	163	0	0	0	0
Treatment Period 1 COMPLETED	151	155	0	0	0	0
Treatment Period 1 NOT COMPLETED	12	8	0	0	0	0
Treatment Period 2 STARTED	0	0	151	51	53	51
Treatment Period 2 COMPLETED	0	0	40	23	25	28
Treatment Period 2 NOT COMPLETED	0	0	111	28	28	23

Reasons for withdrawal

Measure	Placebo Placebo for 12 weeks	Adalimumab Every Week (EW) Adalimumab ew for 12 weeks (160 mg at Week 0; 80 mg at Week 2; and 40 mg ew from Week 4 to Week 12).	Placebo/Placebo Participants randomized to receive placebo in Period 1 received placebo every week from Week 12 to Week 35 in Period 2 (up to 24 weeks).	Adalimumab Every Week (EW)/Placebo Participants randomized to receive adalimumab ew in Period 1 were re-randomized to receive placebo ew from Week 12 to Week 35 in Period 2 (up to 24 weeks).	Adalimumab Every Week (EW)/ Adalimumab Every Other Week (EOW) Participants randomized to receive adalimumab ew in Period 1 were re-randomized to receive 40 mg adalimumab eow from Week 12 to Week 35 in Period 2; placebo injections were administered eow from Week 13 to Week 35 (up to 24 weeks).	Adalimumab Every Week (EW)/Adalimumab Every Week (EW) Participants randomized to receive adalimumab ew in Period 1 were re-randomized to receive 40 mg adalimumab ew from Week 12 to Week 35 in Period 2 (up to 24 weeks).
Treatment Period 1 Adverse Event	5	3	0	0	0	0
Treatment Period 1 Withdrawal by Subject	3	4	0	0	0	0
Treatment Period 1 Lost to Follow-up	3	0	0	0	0	0
Treatment Period 1 Other	1	1	0	0	0	0
Treatment Period 2 Adverse Event	0	0	3	0	2	1
Treatment Period 2 Lack of Efficacy	0	0	9	2	0	1
Treatment Period 2 Withdrawal by Subject	0	0	9	1	1	1
Treatment Period 2 Loss/absence of response (per protocol)	0	0	84	25	22	20
Treatment Period 2 Lost to Follow-up	0	0	3	0	2	0
Treatment Period 2 Other	0	0	3	0	1	0

Baseline Characteristics

Efficacy and Safety Study of Adalimumab in the Treatment of Hidradenitis Suppurativa

Baseline characteristics by cohort

Measure	Placebo n=163 Participants Placebo for 12 weeks	Adalimumab Every Week (EW) n=163 Participants Adalimumab ew for 12 weeks (160 mg at Week 0; 80 mg at Week 2; and 40 mg ew from Week 4 to Week 12).	Total n=326 Participants Total of all reporting groups
Age, Continuous	36.1 years STANDARD_DEVIATION 12.18 • n=5 Participants	34.9 years STANDARD_DEVIATION 9.96 • n=7 Participants	35.5 years STANDARD_DEVIATION 11.13 • n=5 Participants
Sex: Female, Male Female	113 Participants n=5 Participants	108 Participants n=7 Participants	221 Participants n=5 Participants
Sex: Female, Male Male	50 Participants n=5 Participants	55 Participants n=7 Participants	105 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Week 0) up to Week 12

Population: The intention-to-treat (ITT) population, defined as all participants who were randomized at Baseline (Week 0), was analyzed overall and by baseline Hurley Stage

HiSCR was defined as at least a 50% reduction in abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count at Week 12 relative to Baseline. Data are presented for all participants and by baseline Hurley Stage (Stage 1: Abscess formation, single or multiple, without sinus tracts and scarring; Stage II: One or more widely separated recurrent abscesses with tract formation and scars. A participant with at least 1 anatomic region with Hurley Stage II disease and with no anatomic regions with Hurley Stage III disease was classified as Hurley Stage II; and Stage III: Multiple interconnected tracts and abscesses across the entire area, with diffuse or near diffuse involvement. A participant with at least 1 anatomic region with Hurley Stage III disease was classified as Hurley Stage III). Non-responder imputation (NRI): Participants with missing data were considered non-responders.

Outcome measures

Measure	Placebo n=163 Participants Placebo for 12 weeks	Adalimumab Every Week (EW) n=163 Participants Adalimumab ew for 12 weeks (160 mg at Week 0; 80 mg at Week 2; and 40 mg ew from Week 4 to Week 12).	Placebo - Baseline Hurley Stage II n=87 Participants Participants with baseline Hurley Stage II randomized to receive placebo every week (ew) for 12 weeks	Placebo - Baseline Hurley Stage III n=76 Participants Participants with baseline Hurley Stage III randomized to receive placebo every week (ew) for 12 weeks.	Adalimumab Every Week (EW) - Baseline Hurley Stage II n=85 Participants Participants with baseline Hurley Stage II randomized to receive adalimumab ew 160 mg at Week 12, 80 mg at Week 14, and 40 mg ew from Week 16 to 35 (up to 24 weeks).	Adalimumab Every Week (EW) - Baseline Hurley Stage III n=78 Participants Participants with baseline Hurley Stage III randomized to receive adalimumab ew 160 mg at Week 12, 80 mg at Week 14, and 40 mg ew from Week 16 to 35 (up to 24 weeks).
Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12	27.6 percentage of participants	58.9 percentage of participants	36.8 percentage of participants	17.1 percentage of participants	62.4 percentage of participants	55.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 12

Population: Participants in the ITT population with baseline Hurley Stage II

The percentage of participants with AN counts lowered to 0, 1, or 2 at Week 12 among participants with Hurley Stage II at Baseline. NRI: Participants with missing data were considered nonresponders.

Outcome measures

Measure	Placebo n=87 Participants Placebo for 12 weeks	Adalimumab Every Week (EW) n=85 Participants Adalimumab ew for 12 weeks (160 mg at Week 0; 80 mg at Week 2; and 40 mg ew from Week 4 to Week 12).	Placebo - Baseline Hurley Stage II Participants with baseline Hurley Stage II randomized to receive placebo every week (ew) for 12 weeks	Placebo - Baseline Hurley Stage III Participants with baseline Hurley Stage III randomized to receive placebo every week (ew) for 12 weeks.	Adalimumab Every Week (EW) - Baseline Hurley Stage II Participants with baseline Hurley Stage II randomized to receive adalimumab ew 160 mg at Week 12, 80 mg at Week 14, and 40 mg ew from Week 16 to 35 (up to 24 weeks).	Adalimumab Every Week (EW) - Baseline Hurley Stage III Participants with baseline Hurley Stage III randomized to receive adalimumab ew 160 mg at Week 12, 80 mg at Week 14, and 40 mg ew from Week 16 to 35 (up to 24 weeks).
Percentage of Participants With Baseline Hurley Stage II Who Achieved Abscess and Inflammatory Nodule (AN) Count of 0, 1, or 2 at Week 12	32.2 percentage of participants	51.8 percentage of participants	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 12

Population: Participants in the ITT population with baseline NRS at Worst ≥ 3

The Patient's Global Assessment of Skin Pain Numeric Rating Scale (NRS) was used to assess the worst skin pain and the average skin pain due to HS. Ratings for the 2 items range from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). The assessments were completed on a daily diary by participants before they went to bed and responded to the items based on a recall period of the "last 24 hours." The percentage of participants who achieved at least 30% reduction and at least 1 unit reduction from Baseline in the Patient's Global Assessment of Skin Pain (NRS30) - at worst at Week 12 among participants with Baseline NRS ≥ 3 is presented. Weekly averages of daily assessments were analyzed. NRI: Participants with missing data were considered non-responders.

Outcome measures

Measure	Placebo n=111 Participants Placebo for 12 weeks	Adalimumab Every Week (EW) n=105 Participants Adalimumab ew for 12 weeks (160 mg at Week 0; 80 mg at Week 2; and 40 mg ew from Week 4 to Week 12).	Placebo - Baseline Hurley Stage II Participants with baseline Hurley Stage II randomized to receive placebo every week (ew) for 12 weeks	Placebo - Baseline Hurley Stage III Participants with baseline Hurley Stage III randomized to receive placebo every week (ew) for 12 weeks.	Adalimumab Every Week (EW) - Baseline Hurley Stage II Participants with baseline Hurley Stage II randomized to receive adalimumab ew 160 mg at Week 12, 80 mg at Week 14, and 40 mg ew from Week 16 to 35 (up to 24 weeks).	Adalimumab Every Week (EW) - Baseline Hurley Stage III Participants with baseline Hurley Stage III randomized to receive adalimumab ew 160 mg at Week 12, 80 mg at Week 14, and 40 mg ew from Week 16 to 35 (up to 24 weeks).
Percentage of Participants Achieving At Least 30% Reduction and At Least 1 Unit Reduction From Baseline in Patient's Global Assessment of Skin Pain (NRS30) - At Worst at Week 12 Among Participants With Baseline Skin Pain NRS ≥ 3	20.7 percentage of participants	45.7 percentage of participants	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Participants in the ITT population

The Sartorius Scale is used to quantify the severity of HS. Points are awarded for 12 body areas (left and right axillae, left and right sub/inframammary areas, intermammary area, left and right buttocks, left and right inguino-crural folds, perianal area, perineal area, and other): points were awarded for nodules (2 points for each); abscesses (4 points); fistulas (4 points); scars (1 point); other findings (1 point); and longest distance between two lesions (2-6 points, 0 if no lesions); and if lesions are separated by normal skin (yes-0 points; no-6 points). The total Sartorius score is the sum of the 12 regional scores. Last Observation Carried Forward (LOCF): The last completed evaluation from the previous visit within the particular period for efficacy measures was carried forward to impute missing data at later visits in the same period. Baseline efficacy evaluations were not carried forward.

Outcome measures

Measure	Placebo n=162 Participants Placebo for 12 weeks	Adalimumab Every Week (EW) n=163 Participants Adalimumab ew for 12 weeks (160 mg at Week 0; 80 mg at Week 2; and 40 mg ew from Week 4 to Week 12).	Placebo - Baseline Hurley Stage II Participants with baseline Hurley Stage II randomized to receive placebo every week (ew) for 12 weeks	Placebo - Baseline Hurley Stage III Participants with baseline Hurley Stage III randomized to receive placebo every week (ew) for 12 weeks.	Adalimumab Every Week (EW) - Baseline Hurley Stage II Participants with baseline Hurley Stage II randomized to receive adalimumab ew 160 mg at Week 12, 80 mg at Week 14, and 40 mg ew from Week 16 to 35 (up to 24 weeks).	Adalimumab Every Week (EW) - Baseline Hurley Stage III Participants with baseline Hurley Stage III randomized to receive adalimumab ew 160 mg at Week 12, 80 mg at Week 14, and 40 mg ew from Week 16 to 35 (up to 24 weeks).
Change From Baseline to Week 12 in Modified Sartorius Score	-9.5 units on a scale Standard Error 3.84	-28.9 units on a scale Standard Error 3.85	—	—	—	—

Adverse Events

Placebo (Period 1)

Serious events: 6 serious events

Other events: 77 other events

Deaths: 0 deaths

Adalimumab EW (Period 1)

Serious events: 3 serious events

Other events: 66 other events

Deaths: 0 deaths

Placebo/Placebo (Period 2)

Serious events: 7 serious events

Other events: 48 other events

Deaths: 0 deaths

Adalimumab EW/Placebo (Period 2)

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Adalimumab EW/Adalimumab EOW (Period 2)

Serious events: 2 serious events

Other events: 25 other events

Deaths: 0 deaths

Adalimumab EW/Adalimumab EW (Period 2)

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo (Period 1) n=163 participants at risk Placebo for 12 weeks.	Adalimumab EW (Period 1) n=163 participants at risk Adalimumab ew for 12 weeks (160 mg at Week 0; 80 mg at Week 2; and 40 mg ew from Week 4 to Week 12).	Placebo/Placebo (Period 2) n=151 participants at risk Participants randomized to receive placebo in Period 1 received placebo ew from Week 12 to Week 35 in Period 2 (up to 24 weeks).	Adalimumab EW/Placebo (Period 2) n=51 participants at risk Participants randomized to receive adalimumab ew in Period 1 were re-randomized to receive placebo ew from Week 12 to Week 35 in Period 2 (up to 24 weeks).	Adalimumab EW/Adalimumab EOW (Period 2) n=53 participants at risk Participants randomized to receive adalimumab ew in Period 1 were re-randomized to receive 40 mg adalimumab eow from Week 12 to Week 35 in Period 2; placebo injections were administered eow from Week 13 to Week 35 (up to 24 weeks).	Adalimumab EW/Adalimumab EW (Period 2) n=51 participants at risk Participants randomized to receive adalimumab ew in Period 1 were re-randomized to receive 40 mg adalimumab ew from Week 12 to Week 35 in Period 2 (up to 24 weeks).
Blood and lymphatic system disorders ANAEMIA	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Blood and lymphatic system disorders LYMPHADENITIS	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	1.9% 1/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Cardiac disorders ACUTE MYOCARDIAL INFARCTION	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	1.9% 1/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Cardiac disorders ATRIAL FIBRILLATION	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.66% 1/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Cardiac disorders CARDIO-RESPIRATORY ARREST	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	1.9% 1/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
General disorders FATIGUE	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Infections and infestations APPENDICITIS	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.66% 1/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Infections and infestations CLOSTRIDIUM DIFFICILE INFECTION	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.66% 1/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Infections and infestations GASTROENTERITIS	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Infections and infestations INFECTION	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Infections and infestations PNEUMONIA	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Infections and infestations VIRAL INFECTION	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Injury, poisoning and procedural complications ACCIDENTAL OVERDOSE	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Injury, poisoning and procedural complications TENDON RUPTURE	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Investigations INTERNATIONAL NORMALISED RATIO INCREASED	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Metabolism and nutrition disorders DIABETES MELLITUS INADEQUATE CONTROL	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Nervous system disorders DIZZINESS	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Nervous system disorders PRESYNCOPE	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Psychiatric disorders DEPRESSION	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.66% 1/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Psychiatric disorders SUICIDE ATTEMPT	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.66% 1/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Renal and urinary disorders RENAL COLIC	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.66% 1/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Renal and urinary disorders RENAL FAILURE ACUTE	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Skin and subcutaneous tissue disorders HIDRADENITIS	1.2% 2/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.66% 1/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	1.9% 1/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Skin and subcutaneous tissue disorders RASH	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Social circumstances SEXUAL ABUSE	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Surgical and medical procedures ABORTION INDUCED	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.66% 1/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Vascular disorders INTRA-ABDOMINAL HAEMATOMA	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.66% 1/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.

Other adverse events

Measure	Placebo (Period 1) n=163 participants at risk Placebo for 12 weeks.	Adalimumab EW (Period 1) n=163 participants at risk Adalimumab ew for 12 weeks (160 mg at Week 0; 80 mg at Week 2; and 40 mg ew from Week 4 to Week 12).	Placebo/Placebo (Period 2) n=151 participants at risk Participants randomized to receive placebo in Period 1 received placebo ew from Week 12 to Week 35 in Period 2 (up to 24 weeks).	Adalimumab EW/Placebo (Period 2) n=51 participants at risk Participants randomized to receive adalimumab ew in Period 1 were re-randomized to receive placebo ew from Week 12 to Week 35 in Period 2 (up to 24 weeks).	Adalimumab EW/Adalimumab EOW (Period 2) n=53 participants at risk Participants randomized to receive adalimumab ew in Period 1 were re-randomized to receive 40 mg adalimumab eow from Week 12 to Week 35 in Period 2; placebo injections were administered eow from Week 13 to Week 35 (up to 24 weeks).	Adalimumab EW/Adalimumab EW (Period 2) n=51 participants at risk Participants randomized to receive adalimumab ew in Period 1 were re-randomized to receive 40 mg adalimumab ew from Week 12 to Week 35 in Period 2 (up to 24 weeks).
Eye disorders CONJUNCTIVITIS	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	1.3% 2/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	3.9% 2/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	1.9% 1/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Gastrointestinal disorders DIARRHOEA	2.5% 4/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	5.5% 9/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	1.3% 2/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	7.5% 4/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Gastrointestinal disorders NAUSEA	3.1% 5/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	4.3% 7/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	1.9% 1/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Gastrointestinal disorders TOOTHACHE	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	1.2% 2/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 3/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	5.9% 3/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Gastrointestinal disorders VOMITING	1.2% 2/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.5% 4/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	3.8% 2/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
General disorders ASTHENIA	3.7% 6/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	1.3% 2/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
General disorders FATIGUE	1.2% 2/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	3.1% 5/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
General disorders INJECTION SITE PAIN	3.1% 5/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	3.7% 6/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
General disorders PYREXIA	1.2% 2/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	1.3% 2/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	3.8% 2/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Infections and infestations BRONCHITIS	2.5% 4/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	1.2% 2/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	1.3% 2/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	5.9% 3/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Infections and infestations FOLLICULITIS	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.5% 4/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	3.9% 2/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Infections and infestations GASTROENTERITIS	1.8% 3/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	3.1% 5/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	4.6% 7/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	3.8% 2/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Infections and infestations GASTROENTERITIS VIRAL	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	3.8% 2/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	5.9% 3/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Infections and infestations INFLUENZA	1.8% 3/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	1.8% 3/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 3/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	3.9% 2/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	5.9% 3/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Infections and infestations NASOPHARYNGITIS	6.1% 10/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	5.5% 9/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	3.3% 5/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	5.7% 3/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	5.9% 3/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Infections and infestations PHARYNGITIS	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	1.8% 3/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	3.8% 2/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	5.5% 9/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	4.9% 8/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	8.6% 13/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	9.8% 5/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	7.5% 4/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Infections and infestations URINARY TRACT INFECTION	3.1% 5/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 3/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	1.9% 1/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Infections and infestations VIRAL UPPER RESPIRATORY TRACT INFECTION	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	3.9% 2/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Metabolism and nutrition disorders DIABETES MELLITUS	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	3.8% 2/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Metabolism and nutrition disorders VITAMIN D DEFICIENCY	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 1/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	3.8% 2/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Musculoskeletal and connective tissue disorders BACK PAIN	1.8% 3/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	1.8% 3/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.6% 4/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	1.9% 1/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	3.9% 2/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	1.2% 2/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.66% 1/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	3.9% 2/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Nervous system disorders DIZZINESS	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	4.3% 7/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.66% 1/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Nervous system disorders HEADACHE	12.9% 21/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	12.9% 21/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.6% 4/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	7.8% 4/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	5.7% 3/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	9.8% 5/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Psychiatric disorders INSOMNIA	2.5% 4/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	1.3% 2/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Skin and subcutaneous tissue disorders DERMATITIS CONTACT	1.2% 2/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	2.0% 3/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	3.9% 2/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Skin and subcutaneous tissue disorders ERYTHEMA	0.00% 0/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.61% 1/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	3.8% 2/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	0.00% 0/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.
Skin and subcutaneous tissue disorders HIDRADENITIS	11.7% 19/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	4.3% 7/163 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	8.6% 13/151 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	19.6% 10/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	15.1% 8/53 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.	5.9% 3/51 • Adverse Events were collected from first dose of study drug until 70 days following last dose of study drug (46 weeks); Serious Adverse Events were collected from the time that informed consent was obtained (up to 50 weeks). Adverse Events with onset in Period 1 were collected from first dose of study drug until prior to the first dose in Period 2, or up to 70 days following last dose of study drug if the participant discontinued during Period 1.

Additional Information

Global Medical Information

AbbVie (prior sponsor, Abbott)

Phone: 800-633-9110

Results disclosure agreements

• Principal investigator is a sponsor employee AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
• Publication restrictions are in place

Restriction type: OTHER