Trial Outcomes & Findings for A Study Evaluating the Safety, Efficacy, and Pharmacodynamic Effects of ABT-981 in Patients With Knee Osteoarthritis (NCT NCT02087904)

NCT ID: NCT02087904

Last Updated: 2019-08-28

Results Overview

The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) numerical rating scale (NRS). The pain sub-score has a range of 0 (no pain) to 50 (maximum pain). A negative change from baseline indicates improvement.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

350 participants

Primary outcome timeframe

Baseline, Week 16

Results posted on

2019-08-28

Participant Flow

The study included a screening period (approximately 45 days prior to first study drug dose) and a washout period (5 half-lives of the longest acting analgesic used, or 48 hours, whichever was longer, in which all standard of care analgesic medications were discontinued prior to the first study drug dose).

Participant milestones

Participant milestones
Measure	Placebo Matching placebo SC E2W	ABT-981 25 mg 25 mg ABT-981 SC E2W	ABT-981 100 mg 100 mg ABT-981 SC E2W	ABT-981 200 mg 200 mg ABT-981 SC E2W
Overall Study STARTED	85	89	87	89
Overall Study COMPLETED	60	70	65	64
Overall Study NOT COMPLETED	25	19	22	25

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Matching placebo SC E2W	ABT-981 25 mg 25 mg ABT-981 SC E2W	ABT-981 100 mg 100 mg ABT-981 SC E2W	ABT-981 200 mg 200 mg ABT-981 SC E2W
Overall Study Did Not Receive Study Drug	0	0	2	1
Overall Study Adverse Event	8	4	4	12
Overall Study Lack of Efficacy	3	6	3	2
Overall Study Other	6	2	4	4
Overall Study Withdrawal by Subject	8	3	7	4
Overall Study Lost to Follow-up	0	4	2	2

Baseline Characteristics

A Study Evaluating the Safety, Efficacy, and Pharmacodynamic Effects of ABT-981 in Patients With Knee Osteoarthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=85 Participants Matching placebo SC E2W	ABT-981 25 mg n=89 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=85 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=88 Participants 200 mg ABT-981 SC E2W	Total n=347 Participants Total of all reporting groups
Age, Continuous	59.53 years STANDARD_DEVIATION 8.850 • n=5 Participants	61.63 years STANDARD_DEVIATION 7.546 • n=7 Participants	60.21 years STANDARD_DEVIATION 8.194 • n=5 Participants	59.05 years STANDARD_DEVIATION 10.273 • n=4 Participants	60.11 years STANDARD_DEVIATION 8.792 • n=21 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	63 Participants n=7 Participants	53 Participants n=5 Participants	57 Participants n=4 Participants	225 Participants n=21 Participants
Sex: Female, Male Male	33 Participants n=5 Participants	26 Participants n=7 Participants	32 Participants n=5 Participants	31 Participants n=4 Participants	122 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline, Week 16

Population: Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, Last observation carried forward (LOCF; missing responses were imputed by calculation based on the last non-missing post-baseline component values).

Outcome measures

Outcome measures
Measure	Placebo n=85 Participants Matching placebo SC E2W	ABT-981 25 mg n=88 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=84 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=88 Participants 200 mg ABT-981 SC E2W
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Scores of the Index Knee at Week 16	-8.9 score on a scale Interval -10.96 to -6.9	-9.2 score on a scale Interval -11.23 to -7.23	-11.8 score on a scale Interval -13.84 to -9.75	-10.1 score on a scale Interval -12.1 to -8.1

PRIMARY outcome

Timeframe: Baseline, Week 26

Population: Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Change in synovitis of the index knee was evaluated using quantitative magnetic resonance imaging (MRI) measurements. MRI quantitative synovitis of the index knee was defined by mean synovial membrane thickness.

Outcome measures

Outcome measures
Measure	Placebo n=59 Participants Matching placebo SC E2W	ABT-981 25 mg n=65 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=59 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=63 Participants 200 mg ABT-981 SC E2W
Change From Baseline in Quantitative Synovitis of the Index Knee at Week 26	-0.05 mm Interval -0.107 to 0.011	0.01 mm Interval -0.045 to 0.068	-0.08 mm Interval -0.134 to -0.016	0.01 mm Interval -0.047 to 0.067

PRIMARY outcome

Timeframe: Baseline, Week 26

Population: Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Matching placebo SC E2W	ABT-981 25 mg n=69 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=67 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=68 Participants 200 mg ABT-981 SC E2W
Change From Baseline in Effusion Volume of the Index Knee at Week 26	0.03 mL Interval -2.498 to 2.562	0.26 mL Interval -2.113 to 2.624	-1.04 mL Interval -3.421 to 1.347	-1.49 mL Interval -3.868 to 0.898

PRIMARY outcome

Timeframe: Baseline, Week 26

Population: Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Semi-quantitative synovitis/effusion volume WORMS scores were scored as normal (0), \< 33% of maximum estimated distention (1), 33% - 66% of maximum estimated distention (2), or \> 66% of maximum estimated distention (3).

Outcome measures

Outcome measures
Measure	Placebo n=70 Participants Matching placebo SC E2W	ABT-981 25 mg n=76 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=70 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=75 Participants 200 mg ABT-981 SC E2W
Change From Baseline in Whole-Organ Magnetic Resonance Imaging Score (WORMS) Semi-Quantitative Synovitis/Effusion Score of the Index Knee at Week 26	0.07 score on a scale Interval -0.057 to 0.193	-0.01 score on a scale Interval -0.13 to 0.113	-0.08 score on a scale Interval -0.205 to 0.043	-0.07 score on a scale Interval -0.196 to 0.048

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Modified intent to Treat population: all participants who received at least 1 dose of study drug, LOCF (missing responses were imputed by calculation based on the last non-missing post-baseline component values).

The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) NRS. The WOMAC physical function subscale score was 0 (normal) to 170 (least physical function). A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=85 Participants Matching placebo SC E2W	ABT-981 25 mg n=88 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=84 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=87 Participants 200 mg ABT-981 SC E2W
Change From Baseline in WOMAC Physical Function Scores of the Index Knee at Week 16	-28.7 score on a scale Interval -35.3 to -22.15	-29.8 score on a scale Interval -36.27 to -23.32	-36.3 score on a scale Interval -42.9 to -29.69	-32.1 score on a scale Interval -38.64 to -25.63

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: Modified Intent to Treat population: all participants who received at least 1 dose of study drug, LOCF (missing responses were imputed by calculation based on the last non-missing post-baseline component values).

The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) NRS. The WOMAC physical function subscale score was 0 (normal) to 170 (least physical function). A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=85 Participants Matching placebo SC E2W	ABT-981 25 mg n=88 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=84 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=87 Participants 200 mg ABT-981 SC E2W
Change From Baseline in WOMAC Physical Function Scores of the Index Knee at Week 26	-29.7 score on a scale Interval -36.61 to -22.75	-31.8 score on a scale Interval -38.62 to -24.98	-38.9 score on a scale Interval -45.83 to -31.92	-36.9 score on a scale Interval -43.71 to -30.0

SECONDARY outcome

Timeframe: Baseline, Week 52

The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) NRS. The WOMAC physical function subscale score was 0 (normal) to 170 (least physical function). A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=85 Participants Matching placebo SC E2W	ABT-981 25 mg n=88 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=84 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=87 Participants 200 mg ABT-981 SC E2W
Change From Baseline in WOMAC Physical Function Scores of the Index Knee at Week 52	-32.9 score on a scale Interval -40.66 to -25.12	-36.1 score on a scale Interval -43.76 to -28.46	-38.7 score on a scale Interval -46.52 to -30.92	-39.7 score on a scale Interval -47.37 to -32.0

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: Modified intent to Treat population: all subjects who received at least 1 dose of study drug, LOCF (missing responses were imputed by calculation based on the last non-missing post-baseline component values).

Outcome measures

Outcome measures
Measure	Placebo n=85 Participants Matching placebo SC E2W	ABT-981 25 mg n=88 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=84 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=88 Participants 200 mg ABT-981 SC E2W
Change From Baseline in WOMAC Pain Scores of the Index Knee at Week 26	-9.2 score on a scale Interval -11.29 to -7.07	-9.8 score on a scale Interval -11.9 to -7.75	-11.9 score on a scale Interval -13.99 to -9.76	-11.6 score on a scale Interval -13.65 to -9.51

SECONDARY outcome

Timeframe: Baseline, Week 52

Outcome measures

Outcome measures
Measure	Placebo n=85 Participants Matching placebo SC E2W	ABT-981 25 mg n=88 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=84 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=88 Participants 200 mg ABT-981 SC E2W
Change From Baseline in WOMAC Pain Scores of the Index Knee at Week 52	-10.0 score on a scale Interval -12.24 to -7.68	-11.0 score on a scale Interval -13.29 to -8.8	-12.1 score on a scale Interval -14.42 to -9.84	-12.2 score on a scale Interval -14.49 to -10.0

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

BMLs in 15 regions were measured with MRI, and graded as 0 (normal), 1 (mild; \< 25% of region), 2 (moderate; 25% - 50% of region), or 3 (severe; \> 50% of region). The global total BML score was the sum of the 15 component scores, and ranged from 0 (normal) to 45 (severe).

Outcome measures

Outcome measures
Measure	Placebo n=69 Participants Matching placebo SC E2W	ABT-981 25 mg n=76 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=69 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=75 Participants 200 mg ABT-981 SC E2W
Change From Baseline in Global Total Bone Marrow Lesion (BML) Score of the Index Knee Magnetic Resonance Imaging (MRI) at Week 26	0.1 score on a scale Interval -0.24 to 0.43	0.3 score on a scale Interval 0.01 to 0.65	-0.0 score on a scale Interval -0.37 to 0.29	0.1 score on a scale Interval -0.22 to 0.43

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Outcome measures

Outcome measures
Measure	Placebo n=56 Participants Matching placebo SC E2W	ABT-981 25 mg n=66 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=61 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=66 Participants 200 mg ABT-981 SC E2W
Change From Baseline in Global Total BML Score of the Index Knee MRI at Week 52	0.1 score on a scale Interval -0.34 to 0.48	0.2 score on a scale Interval -0.16 to 0.6	0.1 score on a scale Interval -0.3 to 0.48	0.0 score on a scale Interval -0.36 to 0.39

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.

The ICOAP is a multidimensional osteoarthritis-specific measure designed to comprehensively evaluate the pain experience in patients with hip or knee osteoarthritis. The ICOAP includes 11 items (5 constant pain items; 6 intermittent pain items). Each item is rated on a 0 to 4 point scale with a 7-day recall period. The raw maximum intermittent pain score ranges from 0 to 24, transformed to a reported scale of 0 (no pain) to 100 (worst pain). The raw maximum constant pain score ranges from 0 to 20, transformed to a reported scale of 0 (no pain) to 100 (worst pain).

Outcome measures

Outcome measures
Measure	Placebo n=75 Participants Matching placebo SC E2W	ABT-981 25 mg n=84 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=76 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=77 Participants 200 mg ABT-981 SC E2W
Change From Baseline in Index Knee Intermittent and Constant Osteoarthritis Pain (ICOAP) Scores at Week 16 Intermittent Pain	-20.2 score on a scale Interval -24.32 to -16.08	-19.5 score on a scale Interval -23.4 to -15.58	-21.3 score on a scale Interval -25.4 to -17.26	-18.8 score on a scale Interval -22.92 to -14.71
Change From Baseline in Index Knee Intermittent and Constant Osteoarthritis Pain (ICOAP) Scores at Week 16 Constant Pain	-18.6 score on a scale Interval -22.88 to -14.33	-17.7 score on a scale Interval -21.73 to -13.62	-24.2 score on a scale Interval -28.39 to -19.94	-20.0 score on a scale Interval -24.24 to -15.72

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.

Outcome measures

Outcome measures
Measure	Placebo n=68 Participants Matching placebo SC E2W	ABT-981 25 mg n=75 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=72 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=73 Participants 200 mg ABT-981 SC E2W
Change From Baseline in Index Knee ICOAP Scores at Week 26 Intermittent Pain	-18.7 score on a scale Interval -23.21 to -14.21	-19.7 score on a scale Interval -23.99 to -15.42	-21.3 score on a scale Interval -25.66 to -16.98	-21.7 score on a scale Interval -26.11 to -17.38
Change From Baseline in Index Knee ICOAP Scores at Week 26 Constant Pain	-19.6 score on a scale Interval -24.22 to -14.96	-18.8 score on a scale Interval -23.26 to -14.42	-21.6 score on a scale Interval -26.05 to -17.08	-22.1 score on a scale Interval -26.61 to -17.61

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Matching placebo SC E2W	ABT-981 25 mg n=70 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=66 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=66 Participants 200 mg ABT-981 SC E2W
Change From Baseline in Index Knee ICOAP Scores at Week 52 Intermittent Pain	-23.2 score on a scale Interval -28.51 to -17.83	-25.4 score on a scale Interval -30.21 to -20.51	-23.6 score on a scale Interval -28.53 to -18.64	-27.2 score on a scale Interval -32.19 to -22.14
Change From Baseline in Index Knee ICOAP Scores at Week 52 Constant Pain	-20.6 score on a scale Interval -25.93 to -15.21	-21.8 score on a scale Interval -26.7 to -16.94	-25.2 score on a scale Interval -30.14 to -20.17	-29.7 score on a scale Interval -34.78 to -24.66

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

The index knee pain intensity was assessed in 3 different ways using an 11 -point NRS (0 to 10 points representing 'no pain' to 'worst possible pain'). Subjects were asked to enter: 1) average pain intensity during the past week (7-day recall period); 2) the worst pain during activity over the past 24 hours; 3) pain intensity before and after a 40 meter walk (performance pain, before and after). The 40 meter fast paced walk test is a test of short distance walking activity, walking speed over short distances and changing direction during walking. Individuals taking the test should walk as quickly but as safely as possible, without running, along a walkway and then turn around, and repeat again for a total distance of 40 m (132 feet). The total time taken to walk the 40 meters is recorded.

Outcome measures

Outcome measures
Measure	Placebo n=75 Participants Matching placebo SC E2W	ABT-981 25 mg n=84 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=77 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=77 Participants 200 mg ABT-981 SC E2W
Change From Baseline In Index Knee Pain Intensity at Week 16 7-Day Recall Period	-2.4 units on a scale Interval -2.86 to -1.97	-2.4 units on a scale Interval -2.79 to -1.95	-2.7 units on a scale Interval -3.09 to -2.22	-2.1 units on a scale Interval -2.55 to -1.67
Change From Baseline In Index Knee Pain Intensity at Week 16 Activity Pain	-2.3 units on a scale Interval -2.85 to -1.82	-2.4 units on a scale Interval -2.85 to -1.87	-2.7 units on a scale Interval -3.19 to -2.17	-2.1 units on a scale Interval -2.59 to -1.56
Change From Baseline In Index Knee Pain Intensity at Week 16 Performance Pain (Before)	-2.4 units on a scale Interval -2.82 to -1.89	-2.1 units on a scale Interval -2.58 to -1.7	-2.5 units on a scale Interval -2.97 to -2.06	-2.1 units on a scale Interval -2.52 to -1.6
Change From Baseline In Index Knee Pain Intensity at Week 16 Performance Pain (After)	-2.6 units on a scale Interval -3.07 to -2.11	-2.4 units on a scale Interval -2.9 to -2.0	-2.7 units on a scale Interval -3.16 to -2.22	-2.3 units on a scale Interval -2.77 to -1.82

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Outcome measures

Outcome measures
Measure	Placebo n=68 Participants Matching placebo SC E2W	ABT-981 25 mg n=75 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=73 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=73 Participants 200 mg ABT-981 SC E2W
Change From Baseline In Index Knee Pain Intensity at Week 26 7-Day Recall Period	-2.2 units on a scale Interval -2.76 to -1.73	-2.4 units on a scale Interval -2.89 to -1.91	-2.8 units on a scale Interval -3.29 to -2.31	-2.5 units on a scale Interval -2.98 to -1.99
Change From Baseline In Index Knee Pain Intensity at Week 26 Activity Pain	-2.5 units on a scale Interval -3.07 to -1.91	-2.5 units on a scale Interval -3.1 to -1.99	-2.8 units on a scale Interval -3.37 to -2.25	-2.5 units on a scale Interval -3.1 to -1.97
Change From Baseline In Index Knee Pain Intensity at Week 26 Performance Pain (Before)	-2.2 units on a scale Interval -2.72 to -1.7	-2.2 units on a scale Interval -2.68 to -1.71	-2.6 units on a scale Interval -3.13 to -2.16	-2.7 units on a scale Interval -3.15 to -2.17
Change From Baseline In Index Knee Pain Intensity at Week 26 Performance Pain (After)	-2.5 units on a scale Interval -3.01 to -1.98	-2.4 units on a scale Interval -2.9 to -1.92	-3.0 units on a scale Interval -3.53 to -2.54	-2.6 units on a scale Interval -3.13 to -2.13

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Matching placebo SC E2W	ABT-981 25 mg n=70 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=67 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=66 Participants 200 mg ABT-981 SC E2W
Change From Baseline In Index Knee Pain Intensity at Week 52 7-Day Recall Period	-2.9 units on a scale Interval -3.51 to -2.35	-2.9 units on a scale Interval -3.45 to -2.39	-2.9 units on a scale Interval -3.43 to -2.35	-3.1 units on a scale Interval -3.65 to -2.56
Change From Baseline In Index Knee Pain Intensity at Week 52 Activity Pain	-2.8 units on a scale Interval -3.48 to -2.16	-3.0 units on a scale Interval -3.64 to -2.43	-3.2 units on a scale Interval -3.77 to -2.55	-3.0 units on a scale Interval -3.65 to -2.4
Change From Baseline In Index Knee Pain Intensity at Week 52 Performance Pain (Before)	-2.6 units on a scale Interval -3.14 to -2.03	-2.7 units on a scale Interval -3.24 to -2.23	-3.0 units on a scale Interval -3.51 to -2.49	-2.9 units on a scale Interval -3.46 to -2.41
Change From Baseline In Index Knee Pain Intensity at Week 52 Performance Pain (After)	-2.9 units on a scale Interval -3.47 to -2.33	-3.0 units on a scale Interval -3.53 to -2.5	-3.4 units on a scale Interval -3.9 to -2.86	-3.2 units on a scale Interval -3.69 to -2.62

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

The PGA is a single item for evaluating overall osteoarthritis disease activity. PGA is assessed using an 11-point NRS of 0 to 10 points (representing best to worst disease status, respectively), with a 7-day recall period.

Outcome measures

Outcome measures
Measure	Placebo n=75 Participants Matching placebo SC E2W	ABT-981 25 mg n=84 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=77 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=77 Participants 200 mg ABT-981 SC E2W
Change From Baseline in Patient Global Assessment (PGA) of Arthritis of the Index Knee at Week 16	-2.5 units on a scale Interval -2.94 to -2.01	-2.4 units on a scale Interval -2.8 to -1.92	-2.9 units on a scale Interval -3.34 to -2.42	-2.6 units on a scale Interval -3.08 to -2.15

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Outcome measures

Outcome measures
Measure	Placebo n=68 Participants Matching placebo SC E2W	ABT-981 25 mg n=75 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=73 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=73 Participants 200 mg ABT-981 SC E2W
Change From Baseline in PGA of Arthritis of the Index Knee at Week 26	-2.4 units on a scale Interval -2.96 to -1.91	-2.4 units on a scale Interval -2.94 to -1.94	-3.0 units on a scale Interval -3.48 to -2.47	-2.7 units on a scale Interval -3.18 to -2.16

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Matching placebo SC E2W	ABT-981 25 mg n=70 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=67 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=66 Participants 200 mg ABT-981 SC E2W
Change From Baseline in PGA of Arthritis of the Index Knee at Week 52	-3.0 units on a scale Interval -3.62 to -2.44	-2.9 units on a scale Interval -3.48 to -2.41	-3.2 units on a scale Interval -3.71 to -2.62	-3.5 units on a scale Interval -4.01 to -2.89

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Cartilage volume of the global knee, the medial central condyle + plateau, and the medial condyle + plateau was measured using MRI.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Matching placebo SC E2W	ABT-981 25 mg n=65 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=53 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=66 Participants 200 mg ABT-981 SC E2W
Change From Baseline in Cartilage Volume of the Index Knee at Week 26 Global Knee	-326.0 mm^3 Interval -400.83 to -251.13	-325.5 mm^3 Interval -397.1 to -253.83	-322.4 mm^3 Interval -400.2 to -244.61	-359.0 mm^3 Interval -429.72 to -288.35
Change From Baseline in Cartilage Volume of the Index Knee at Week 26 Medial Central Condyle + Plateau	-59.1 mm^3 Interval -83.12 to -35.1	-54.9 mm^3 Interval -77.83 to -31.9	-50.1 mm^3 Interval -75.13 to -25.07	-57.5 mm^3 Interval -80.12 to -34.88
Change From Baseline in Cartilage Volume of the Index Knee at Week 26 Medial Condyle + Plateau	-128.6 mm^3 Interval -166.76 to -90.5	-126.5 mm^3 Interval -163.03 to -90.02	-124.5 mm^3 Interval -164.13 to -84.86	-114.9 mm^3 Interval -150.86 to -78.9

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Cartilage volume of the global knee, the medial central condyle + plateau, and the medial condyle + plateau was measured using MRI.

Outcome measures

Outcome measures
Measure	Placebo n=49 Participants Matching placebo SC E2W	ABT-981 25 mg n=57 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=50 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=56 Participants 200 mg ABT-981 SC E2W
Change From Baseline in Cartilage Volume of the Index Knee at Week 52 Global Knee	-557.0 mm^3 Interval -659.86 to -454.1	-598.7 mm^3 Interval -694.66 to -502.76	-554.3 mm^3 Interval -654.92 to -453.6	-583.1 mm^3 Interval -678.88 to -487.23
Change From Baseline in Cartilage Volume of the Index Knee at Week 52 Medial Central Condyle + Plateau	-101.2 mm^3 Interval -134.56 to -67.79	-126.3 mm^3 Interval -157.5 to -95.09	-90.1 mm^3 Interval -122.89 to -57.29	-113.0 mm^3 Interval -144.08 to -81.84
Change From Baseline in Cartilage Volume of the Index Knee at Week 52 Medial Condyle + Plateau	-214.7 mm^3 Interval -273.77 to -155.64	-255.0 mm^3 Interval -310.03 to -199.97	-190.3 mm^3 Interval -248.05 to -132.51	-242.8 mm^3 Interval -297.71 to -187.86

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Cartilage thickness of the global knee, the medial central condyle + plateau, and the medial condyle + plateau was measured using MRI.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Matching placebo SC E2W	ABT-981 25 mg n=65 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=53 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=66 Participants 200 mg ABT-981 SC E2W
Change From Baseline in Cartilage Thickness of the Index Knee at Week 26 Global Knee	-0.047 mm Interval -0.058 to -0.036	-0.047 mm Interval -0.058 to -0.037	-0.048 mm Interval -0.059 to -0.037	-0.052 mm Interval -0.062 to -0.041
Change From Baseline in Cartilage Thickness of the Index Knee at Week 26 Medial Central Condyle + Plateau	-0.085 mm Interval -0.122 to -0.048	-0.077 mm Interval -0.113 to -0.042	-0.074 mm Interval -0.113 to -0.036	-0.076 mm Interval -0.111 to -0.041
Change From Baseline in Cartilage Thickness of the Index Knee at Week 26 Medial Condyle + Plateau	-0.046 mm Interval -0.06 to -0.031	-0.045 mm Interval -0.059 to -0.031	-0.047 mm Interval -0.062 to -0.032	-0.044 mm Interval -0.058 to -0.031

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Cartilage thickness of the global knee, the medial central condyle + plateau, and the medial condyle + plateau was measured using MRI.

Outcome measures

Outcome measures
Measure	Placebo n=49 Participants Matching placebo SC E2W	ABT-981 25 mg n=57 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=50 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=56 Participants 200 mg ABT-981 SC E2W
Change From Baseline in Cartilage Thickness of the Index Knee at Week 52 Global Knee	-0.081 mm Interval -0.095 to -0.066	-0.085 mm Interval -0.099 to -0.072	-0.081 mm Interval -0.095 to -0.067	-0.083 mm Interval -0.097 to -0.07
Change From Baseline in Cartilage Thickness of the Index Knee at Week 52 Medial Central Condyle + Plateau	-0.136 mm Interval -0.187 to -0.084	-0.176 mm Interval -0.224 to -0.127	-0.113 mm Interval -0.163 to -0.062	-0.141 mm Interval -0.19 to -0.093
Change From Baseline in Cartilage Thickness of the Index Knee at Week 52 Medial Condyle + Plateau	-0.084 mm Interval -0.106 to -0.063	-0.096 mm Interval -0.117 to -0.076	-0.073 mm Interval -0.094 to -0.052	-0.087 mm Interval -0.107 to -0.067

SECONDARY outcome

Timeframe: Week 16

Population: Modified Intent to Treat population: all participants who received at least 1 dose of study drug, LOCF.

Percentage of participants classified as OMERACT-OARSI responders at Week 16. A subject was considered an OMERACT-OARSI responder if any of the following 3 criteria were met: 1. WOMAC Pain (in 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 2. WOMAC Function (in normalized 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 3. At least 2 of the following 3 are met: WOMAC Pain improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; WOMAC Function improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; PGA improvement ≥ 20% and absolute change (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline. Response rate 95% confidence interval based on normal approximation.

Outcome measures

Outcome measures
Measure	Placebo n=85 Participants Matching placebo SC E2W	ABT-981 25 mg n=88 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=84 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=87 Participants 200 mg ABT-981 SC E2W
Outcome Measures in Rheumatology Clinical Trials/Osteoarthritis Research Society International (OMERACT/OARSI) Response Rate at Week 16	60.0 percentage of participants Interval 49.6 to 70.4	67.0 percentage of participants Interval 57.2 to 76.9	72.6 percentage of participants Interval 63.1 to 82.2	65.5 percentage of participants Interval 55.5 to 75.5

SECONDARY outcome

Timeframe: Week 26

Population: Modified Intent to Treat population: all participants who received at least 1 dose of study drug, LOCF.

Percentage of participants classified as OMERACT-OARSI responders at Week 26. A subject was considered an OMERACT-OARSI responder if any of the following 3 criteria were met: 1. WOMAC Pain (in 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 2. WOMAC Function (in normalized 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 3. At least 2 of the following 3 are met: WOMAC Pain improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; WOMAC Function improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; PGA improvement ≥ 20% and absolute change (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline. Response rate 95% confidence interval based on normal approximation.

Outcome measures

Outcome measures
Measure	Placebo n=85 Participants Matching placebo SC E2W	ABT-981 25 mg n=88 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=84 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=88 Participants 200 mg ABT-981 SC E2W
Outcome Measures in Rheumatology Clinical Trials/Osteoarthritis Research Society International (OMERACT/OARSI) Response Rate at Week 26	62.4 percentage of participants Interval 52.1 to 72.7	64.8 percentage of participants Interval 54.8 to 74.8	66.7 percentage of participants Interval 56.6 to 76.7	72.7 percentage of participants Interval 63.4 to 82.0

SECONDARY outcome

Timeframe: Week 52

Population: Modified Intent to Treat population: all participants who received at least 1 dose of study drug, LOCF.

Percentage of participants classified as OMERACT-OARSI responders at Week 52. A subject was considered an OMERACT-OARSI responder if any of the following 3 criteria were met: 1. WOMAC Pain (in 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 2. WOMAC Function (in normalized 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 3. At least 2 of the following 3 are met: WOMAC Pain improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; WOMAC Function improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; PGA improvement ≥ 20% and absolute change (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline. Response rate 95% confidence interval based on normal approximation.

Outcome measures

Outcome measures
Measure	Placebo n=85 Participants Matching placebo SC E2W	ABT-981 25 mg n=88 Participants 25 mg ABT-981 SC E2W	ABT-981 100 mg n=84 Participants 100 mg ABT-981 SC E2W	ABT-981 200 mg n=88 Participants 200 mg ABT-981 SC E2W
Outcome Measures in Rheumatology Clinical Trials/Osteoarthritis Research Society International (OMERACT/OARSI) Response Rate at Week 52	70.6 percentage of participants Interval 60.9 to 80.3	69.3 percentage of participants Interval 59.7 to 79.0	71.4 percentage of participants Interval 61.8 to 81.1	72.7 percentage of participants Interval 63.4 to 82.0

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 66 other events

Deaths: 0 deaths

ABT-981 25 mg

Serious events: 11 serious events

Other events: 63 other events

Deaths: 0 deaths

ABT-981 100 mg

Serious events: 8 serious events

Other events: 65 other events

Deaths: 0 deaths

ABT-981 200 mg

Serious events: 4 serious events

Other events: 75 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Global Medical Services

AbbVie

Phone: AbbVie

Email: [email protected]

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

Measure	Placebo n=85 participants at risk Matching placebo SC E2W	ABT-981 25 mg n=89 participants at risk 25 mg ABT-981 SC E2W	ABT-981 100 mg n=85 participants at risk 100 mg ABT-981 SC E2W	ABT-981 200 mg n=88 participants at risk 200 mg ABT-981 SC E2W
Blood and lymphatic system disorders NEUTROPENIA	1.2% 1/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	13.5% 12/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	14.1% 12/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	23.9% 21/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Gastrointestinal disorders DIARRHOEA	8.2% 7/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	6.7% 6/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	5.9% 5/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	10.2% 9/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Gastrointestinal disorders NAUSEA	3.5% 3/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	4.5% 4/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	7.1% 6/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	6.8% 6/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
General disorders FATIGUE	14.1% 12/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	4.5% 4/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	5.9% 5/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	8.0% 7/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
General disorders INJECTION SITE ERYTHEMA	1.2% 1/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	4.5% 4/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	8.2% 7/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	5.7% 5/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
General disorders INJECTION SITE PAIN	8.2% 7/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	2.2% 2/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	2.4% 2/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	1.1% 1/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
General disorders INJECTION SITE RASH	3.5% 3/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	3.4% 3/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	8.2% 7/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	9.1% 8/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
General disorders INJECTION SITE REACTION	0.00% 0/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	6.7% 6/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	9.4% 8/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	13.6% 12/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
General disorders PAIN	7.1% 6/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	3.4% 3/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	4.7% 4/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	4.5% 4/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Infections and infestations BRONCHITIS	2.4% 2/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	5.6% 5/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	1.2% 1/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	4.5% 4/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Infections and infestations INFLUENZA	11.8% 10/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	2.2% 2/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	5.9% 5/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	4.5% 4/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Infections and infestations NASOPHARYNGITIS	18.8% 16/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	10.1% 9/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	15.3% 13/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	19.3% 17/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Infections and infestations SINUSITIS	1.2% 1/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	5.6% 5/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	3.5% 3/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	3.4% 3/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	9.4% 8/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	9.0% 8/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	8.2% 7/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	13.6% 12/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Infections and infestations URINARY TRACT INFECTION	4.7% 4/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	3.4% 3/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	5.9% 5/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	9.1% 8/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Injury, poisoning and procedural complications CONTUSION	3.5% 3/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	10.1% 9/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	2.4% 2/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	5.7% 5/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Injury, poisoning and procedural complications FALL	3.5% 3/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	5.6% 5/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	3.5% 3/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	9.1% 8/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Injury, poisoning and procedural complications LIGAMENT SPRAIN	3.5% 3/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	6.7% 6/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	2.4% 2/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	2.3% 2/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Investigations NEUTROPHIL COUNT DECREASED	1.2% 1/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	3.4% 3/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	15.3% 13/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	14.8% 13/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Musculoskeletal and connective tissue disorders ARTHRALGIA	18.8% 16/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	18.0% 16/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	22.4% 19/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	15.9% 14/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Musculoskeletal and connective tissue disorders BACK PAIN	16.5% 14/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	9.0% 8/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	12.9% 11/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	15.9% 14/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	5.9% 5/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	5.6% 5/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	4.7% 4/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	4.5% 4/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Musculoskeletal and connective tissue disorders MYALGIA	1.2% 1/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	2.2% 2/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	3.5% 3/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	10.2% 9/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	7.1% 6/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	5.6% 5/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	8.2% 7/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	5.7% 5/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Nervous system disorders DIZZINESS	1.2% 1/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	3.4% 3/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	7.1% 6/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	3.4% 3/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Nervous system disorders HEADACHE	25.9% 22/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	15.7% 14/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	16.5% 14/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	23.9% 21/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders COUGH	5.9% 5/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	7.9% 7/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	5.9% 5/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	5.7% 5/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	2.4% 2/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	4.5% 4/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	5.9% 5/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	8.0% 7/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Skin and subcutaneous tissue disorders PRURITUS	0.00% 0/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	6.7% 6/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	5.9% 5/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	4.5% 4/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Skin and subcutaneous tissue disorders RASH	3.5% 3/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	2.2% 2/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	7.1% 6/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	4.5% 4/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.
Vascular disorders HYPERTENSION	7.1% 6/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	7.9% 7/89 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	5.9% 5/85 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.	1.1% 1/88 • up to Week 52 (or last dose of study drug) plus 70 days Safety population: all participants who took at least one dose of study drug.