Trial Outcomes & Findings for Phase ll Study of Pirfenidone in Patients With RAILD (TRAIL1) (NCT NCT02808871)

Results Overview

Number of participants who developed any element of the composite endpoint of decline in percent predicted FVC of 10% or greater or death.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

123 participants

Primary outcome timeframe

52 weeks

Results posted on

2022-08-16

Participant Flow

Participant milestones

Participant milestones
Measure	Pirfenidone Pirfenidone 2403 mg/d for 52 weeks Pirfenidone: Pirfenidone three times daily (2403 mg) for 52 weeks	Placebo Placebo for 52 weeks Placebo: Placebo three times daily for 52 weeks
Overall Study STARTED	63	60
Overall Study COMPLETED	52	51
Overall Study NOT COMPLETED	11	9

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase ll Study of Pirfenidone in Patients With RAILD (TRAIL1)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pirfenidone n=63 Participants Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 Participants Placebo for 52 weeks	Total n=123 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	27 Participants n=99 Participants	18 Participants n=107 Participants	45 Participants n=206 Participants
Age, Categorical >=65 years	36 Participants n=99 Participants	42 Participants n=107 Participants	78 Participants n=206 Participants
Age, Continuous	66.6 years STANDARD_DEVIATION 8.2 • n=99 Participants	68.1 years STANDARD_DEVIATION 9.1 • n=107 Participants	67.3 years STANDARD_DEVIATION 8.6 • n=206 Participants
Sex: Female, Male Female	25 Participants n=99 Participants	21 Participants n=107 Participants	46 Participants n=206 Participants
Sex: Female, Male Male	38 Participants n=99 Participants	39 Participants n=107 Participants	77 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Asian	4 Participants n=99 Participants	0 Participants n=107 Participants	4 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) White	56 Participants n=99 Participants	56 Participants n=107 Participants	112 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	3 Participants n=107 Participants	3 Participants n=206 Participants
Region of Enrollment Canada	6 participants n=99 Participants	5 participants n=107 Participants	11 participants n=206 Participants
Region of Enrollment United States	25 participants n=99 Participants	23 participants n=107 Participants	48 participants n=206 Participants
Region of Enrollment United Kingdom	27 participants n=99 Participants	27 participants n=107 Participants	54 participants n=206 Participants
Region of Enrollment Australia	5 participants n=99 Participants	5 participants n=107 Participants	10 participants n=206 Participants

PRIMARY outcome

Timeframe: 52 weeks

Number of participants who developed any element of the composite endpoint of decline in percent predicted FVC of 10% or greater or death.

Outcome measures

Outcome measures
Measure	Pirfenidone n=63 Participants Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 Participants Placebo for 52 weeks
Number of Participants Who Developed Any Element of the Composite Endpoint	7 Participants	9 Participants

SECONDARY outcome

Timeframe: 52 weeks

Number of participants with decline from baseline in percent predicted FVC of 10% or greater during the study period.

Outcome measures

Outcome measures
Measure	Pirfenidone n=63 Participants Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 Participants Placebo for 52 weeks
Number of Participants With FVC Decline From Baseline of 10% or Greater	5 Participants	7 Participants

SECONDARY outcome

Timeframe: 52 weeks

Number of participants with progressive disease as defined by OMERACT: FVC% relative decline of \>=10% or FVC% change in \>=5\< 10% and \>=15% diffusing capacity (DLCO)

Outcome measures

Outcome measures
Measure	Pirfenidone n=63 Participants Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 Participants Placebo for 52 weeks
Number of Participants With Progressive Disease	16 Participants	19 Participants

SECONDARY outcome

Timeframe: 52 weeks

Change from baseline to end of study in absolute value of FVC over the 52 week study period

Outcome measures

Outcome measures
Measure	Pirfenidone n=63 Participants Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 Participants Placebo for 52 weeks
Change in Absolute Value FVC Over the 52 Week Study Period	-66 ml Standard Deviation 20	-146 ml Standard Deviation 20

SECONDARY outcome

Timeframe: 52 weeks

Change from baseline to end of study of percent predicted FVC over the 52 week study period

Outcome measures

Outcome measures
Measure	Pirfenidone n=63 Participants Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 Participants Placebo for 52 weeks
Change in % Predicted FVC From Baseline to End of Study Over the 52 Week Study Period	-1.02 % predicted Standard Deviation 0.51	-3.21 % predicted Standard Deviation 0.52

SECONDARY outcome

Timeframe: 52 weeks

Time to decline of 10% or greater in percent predicted FVC or death while on study

Outcome measures

Outcome measures
Measure	Pirfenidone n=63 Participants Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 Participants Placebo for 52 weeks
Time to Composite of Decline in FVC or Death	349.5 days Standard Error 7.2	339.9 days Standard Error 10.2

SECONDARY outcome

Timeframe: 52 weeks

Change from Baseline to end of study in dyspnea, as measured by the Dyspnea 12 questionnaire - Total scores range from 0 to 36, with higher scores corresponding to greater severity.

Outcome measures

Outcome measures
Measure	Pirfenidone n=63 Participants Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 Participants Placebo for 52 weeks
Change in PRO of Dyspnea	0.45 score Standard Deviation 0.71	1.37 score Standard Deviation 0.72

SECONDARY outcome

Timeframe: 52 weeks

Number of participants experiencing mortality due to all causes

Outcome measures

Outcome measures
Measure	Pirfenidone n=63 Participants Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 Participants Placebo for 52 weeks
All-cause Mortality	2 Participants	3 Participants

SECONDARY outcome

Timeframe: 52 weeks

Number of participants requiring hospitalization for any cause

Outcome measures

Outcome measures
Measure	Pirfenidone n=63 Participants Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 Participants Placebo for 52 weeks
All Cause Hospitalization	7 Participants	7 Participants

SECONDARY outcome

Timeframe: 52 weeks

Number of participants requiring hospitalization for respiratory cause

Outcome measures

Outcome measures
Measure	Pirfenidone n=63 Participants Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 Participants Placebo for 52 weeks
Hospitalization for Respiratory Cause	2 Participants	5 Participants

SECONDARY outcome

Timeframe: 52 weeks

Number of participants experiencing acute exacerbation requiring hospitalization

Outcome measures

Outcome measures
Measure	Pirfenidone n=63 Participants Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 Participants Placebo for 52 weeks
Acute Exacerbations Requiring Hospitalization	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 52 weeks

Number of participants with treatment-emergent adverse events (AEs)

Outcome measures

Outcome measures
Measure	Pirfenidone n=62 Participants Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 Participants Placebo for 52 weeks
Treatment-emergent Adverse Events (AEs)	62 Participants	56 Participants

SECONDARY outcome

Timeframe: 52 weeks

Number of participants with treatment-emergent serious adverse events (SAEs) in the as treated population

Outcome measures

Outcome measures
Measure	Pirfenidone n=62 Participants Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 Participants Placebo for 52 weeks
Treatment-emergent Serious Adverse Events (SAEs)	9 Participants	8 Participants

SECONDARY outcome

Timeframe: 52 weeks

Number of participants with treatment-emergent/treatment-related AEs

Outcome measures

Outcome measures
Measure	Pirfenidone n=62 Participants Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 Participants Placebo for 52 weeks
Treatment-emergent/Treatment-related AEs	27 Participants	18 Participants

SECONDARY outcome

Timeframe: 52 weeks

Number of participants with treatment-emergent/treatment-related SAEs

Outcome measures

Outcome measures
Measure	Pirfenidone n=62 Participants Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 Participants Placebo for 52 weeks
Treatment-emergent/Treatment-related SAEs	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 52 weeks

Number of participants with AEs leading to early discontinuation of study treatment

Outcome measures

Outcome measures
Measure	Pirfenidone n=62 Participants Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 Participants Placebo for 52 weeks
AEs Leading to Early Discontinuation of Study Treatment	15 Participants	6 Participants

SECONDARY outcome

Timeframe: 52 weeks

Number of participants who experienced treatment-emergent death or transplant

Outcome measures

Outcome measures
Measure	Pirfenidone n=62 Participants Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 Participants Placebo for 52 weeks
Treatment-emergent Death or Transplant	2 Participants	4 Participants

SECONDARY outcome

Timeframe: 52 weeks

Number of participants who experienced treatment-emergent RA-ILD-related mortality

Outcome measures

Outcome measures
Measure	Pirfenidone n=62 Participants Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 Participants Placebo for 52 weeks
Treatment-emergent RA-ILD-related Mortality	1 Participants	0 Participants

Adverse Events

Pirfenidone

Serious events: 10 serious events

Other events: 62 other events

Deaths: 2 deaths

Placebo

Serious events: 11 serious events

Other events: 56 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Pirfenidone n=62 participants at risk Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 participants at risk Placebo for 52 weeks
Cardiac disorders Cardiac	4.8% 3/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	0.00% 0/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Gastrointestinal disorders Gastrointestinal	1.6% 1/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	1.7% 1/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Immune system disorders Immune System	1.6% 1/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	0.00% 0/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Infections and infestations Infections and Infestations	4.8% 3/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	5.0% 3/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Musculoskeletal and connective tissue disorders Musculoskeletal and Connective Tissue	0.00% 0/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	3.3% 2/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Nervous system disorders Nervous System	0.00% 0/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	3.3% 2/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Respiratory, thoracic and mediastinal disorders Respiratory, Thoracic and Mediastinal	3.2% 2/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	5.0% 3/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.

Other adverse events

Additional Information

Ivan O. Rosas, MD

Baylor College of Medicine

Phone: 617-510-9910

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Pirfenidone n=62 participants at risk Pirfenidone 2403 mg/d for 52 weeks	Placebo n=60 participants at risk Placebo for 52 weeks
Blood and lymphatic system disorders Blood and Lymphatic System	11.3% 7/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	10.0% 6/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Cardiac disorders Cardiac	19.4% 12/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	15.0% 9/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Ear and labyrinth disorders Ear and Labyrinth	8.1% 5/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	3.3% 2/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Endocrine disorders Endocrine	1.6% 1/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	1.7% 1/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Eye disorders Eye	12.9% 8/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	6.7% 4/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Gastrointestinal disorders Gastrointestinal	80.6% 50/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	60.0% 36/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
General disorders General	59.7% 37/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	46.7% 28/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Hepatobiliary disorders Hepatobiliary	8.1% 5/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	3.3% 2/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Immune system disorders Immune System	6.5% 4/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	5.0% 3/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Infections and infestations Infections and Infestations	37.1% 23/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	36.7% 22/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Injury, poisoning and procedural complications Injury, Poisoning and Procedural	1.6% 1/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	6.7% 4/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Investigations Investigations	0.00% 0/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	1.7% 1/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Metabolism and nutrition disorders Metabolism and Nutrition	9.7% 6/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	6.7% 4/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Musculoskeletal and connective tissue disorders Musculoskeletal and Connective Tissue	48.4% 30/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	38.3% 23/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Nervous system disorders Nervous System	9.7% 6/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	11.7% 7/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Psychiatric disorders Psychiatric	8.1% 5/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	3.3% 2/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Renal and urinary disorders Renal and Urinary	3.2% 2/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	8.3% 5/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Reproductive system and breast disorders Reproductive System and Breast	1.6% 1/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	1.7% 1/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Respiratory, thoracic and mediastinal disorders Respiratory, Thoracic and Mediastinal	54.8% 34/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	53.3% 32/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Skin and subcutaneous tissue disorders Skin and Subcutaneous Tissue	32.3% 20/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	25.0% 15/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.
Surgical and medical procedures Surgical and Medical Procedures	4.8% 3/62 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.	1.7% 1/60 • Each participant was assessed for development of AE's from time of first dose of study drug through last study visit (56 weeks) or until withdrawal from study. Mean time period of AE monitoring per study subject was 51.5 weeks (SD 12.86). Adverse Events were monitored/assessed according to system/class without regard to the specific Adverse Event Term. Adverse events were measured in the as treated population.