Trial Outcomes & Findings for Macitentan for the Treatment of Digital Ulcers in Systemic Sclerosis Patients (NCT NCT01474122)

Last Updated: 2025-02-04

Results Overview

DUs were assessed at each visit starting with the screening visit. Only DUs from the proximal interphalangeal joint (PIP) distally (both on the dorsal and volar surface of the hand, including the digital tip) were recorded. The location of each DU was noted. At each subsequent visit the location of each new DU was noted. DUs that occurred and healed between visits and were reported by patients were not recorded as new DUs. The evaluation was performed by an experienced physician or a trained rater with expertise in the assessment of DUs in systemic sclerosis (SSc). For a given patient, DUs were assessed by the same rater at each visit, whenever possible. Any DU that developed over a previously healed ulcer was recorded as a new DU. Incidence rate is adjusted for 16 weeks of observation, hence is calculated as the number of new DUs/total number of observation days.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

265 participants

Primary outcome timeframe

Baseline to Week 16

Results posted on

2025-02-04

Participant Flow

Conducted at 73 centers in 20 countries.The first patient randomized was 9 Feb 2012 and last patient, last visit was 6 Feb 2014.

A screening visit was performed between Day -14 and Day -1 of the study. Of the 324 patients screened for the study, 59 were screen failures.

Participant milestones

Participant milestones
Measure	Macitentan 3mg Patients received macitentan once daily at a dose of 3 mg.	Macitentan 10mg Patients received macitentan once daily at a dose of 10 mg.	Placebo Patients received placebo once daily.
Period 1: Baseline to Week 16 STARTED	88	88	89
Period 1: Baseline to Week 16 COMPLETED	87	86	88
Period 1: Baseline to Week 16 NOT COMPLETED	1	2	1
Period 2: Week 16 to End of Study STARTED	87	86	88
Period 2: Week 16 to End of Study COMPLETED	70	73	73
Period 2: Week 16 to End of Study NOT COMPLETED	17	13	15

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Macitentan for the Treatment of Digital Ulcers in Systemic Sclerosis Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Macitentan 3mg n=88 Participants Patients received macitentan once daily at a dose of 3 mg.	Macitentan 10mg n=88 Participants Patients received macitentan once daily at a dose of 10 mg.	Placebo n=89 Participants Patients received placebo once daily.	Total n=265 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	76 Participants n=5 Participants	83 Participants n=7 Participants	75 Participants n=5 Participants	234 Participants n=4 Participants
Age, Categorical >=65 years	12 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants	31 Participants n=4 Participants
Age, Continuous	50.6 years STANDARD_DEVIATION 13.20 • n=5 Participants	47.4 years STANDARD_DEVIATION 13.02 • n=7 Participants	50.6 years STANDARD_DEVIATION 12.88 • n=5 Participants	49.6 years STANDARD_DEVIATION 13.06 • n=4 Participants
Sex: Female, Male Female	75 Participants n=5 Participants	71 Participants n=7 Participants	71 Participants n=5 Participants	217 Participants n=4 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	17 Participants n=7 Participants	18 Participants n=5 Participants	48 Participants n=4 Participants
Race/Ethnicity, Customized White	62 participants n=5 Participants	63 participants n=7 Participants	68 participants n=5 Participants	193 participants n=4 Participants
Race/Ethnicity, Customized Black or African American	2 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
Race/Ethnicity, Customized Asian	6 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants	16 participants n=4 Participants
Race/Ethnicity, Customized Hispanic	12 participants n=5 Participants	14 participants n=7 Participants	9 participants n=5 Participants	35 participants n=4 Participants
Race/Ethnicity, Customized Other	6 participants n=5 Participants	7 participants n=7 Participants	6 participants n=5 Participants	19 participants n=4 Participants
Region of Enrollment Argentina	12 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	18 participants n=4 Participants
Region of Enrollment Belgium	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Region of Enrollment China	3 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants	11 participants n=4 Participants
Region of Enrollment Colombia	3 participants n=5 Participants	5 participants n=7 Participants	6 participants n=5 Participants	14 participants n=4 Participants
Region of Enrollment Germany	2 participants n=5 Participants	3 participants n=7 Participants	2 participants n=5 Participants	7 participants n=4 Participants
Region of Enrollment Greece	2 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants	11 participants n=4 Participants
Region of Enrollment Ireland	1 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	4 participants n=4 Participants
Region of Enrollment Israel	5 participants n=5 Participants	7 participants n=7 Participants	12 participants n=5 Participants	24 participants n=4 Participants
Region of Enrollment Mexico	6 participants n=5 Participants	9 participants n=7 Participants	6 participants n=5 Participants	21 participants n=4 Participants
Region of Enrollment Netherlands	3 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	6 participants n=4 Participants
Region of Enrollment New Zealand	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants	6 participants n=4 Participants
Region of Enrollment Poland	7 participants n=5 Participants	11 participants n=7 Participants	5 participants n=5 Participants	23 participants n=4 Participants
Region of Enrollment Portugal	1 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants	7 participants n=4 Participants
Region of Enrollment Puerto Rico	1 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
Region of Enrollment Russian Federation	5 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants	16 participants n=4 Participants
Region of Enrollment South Africa	3 participants n=5 Participants	4 participants n=7 Participants	2 participants n=5 Participants	9 participants n=4 Participants
Region of Enrollment Turkey	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Region of Enrollment Ukraine	9 participants n=5 Participants	7 participants n=7 Participants	4 participants n=5 Participants	20 participants n=4 Participants
Region of Enrollment United Kingdom	7 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants	16 participants n=4 Participants
Region of Enrollment United States	16 participants n=5 Participants	16 participants n=7 Participants	16 participants n=5 Participants	48 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline to Week 16

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Macitentan 3mg n=88 Participants Patients received macitentan once daily at a dose of 3 mg.	Macitentan 10mg n=88 Participants Patients received macitentan once daily at a dose of 10 mg.	Placebo n=89 Participants Patients received placebo once daily.
Incidence Rate of New Digital Ulcers (DUs) up to Week 16	1.4413 new DUs/16 weeks	1.3636 new DUs/16 weeks	1.1049 new DUs/16 weeks

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Modified intention to treat set. Ten patients were excluded from the modified intent to treat set due to protocol violations.

DUs were assessed at each visit starting with the screening visit. Only DUs from the proximal interphalangeal joint (PIP) distally (both on the dorsal and volar surface of the hand, including the digital tip) were recorded. The location of each DU was noted. At each subsequent visit the location of each new DU was noted. DUs that occurred and healed between visits and were reported by patients were not recorded as new DUs. The evaluation was performed by an experienced physician or a trained rater with expertise in the assessment of DUs in systemic sclerosis (SSc). For a given patient, DUs were assessed by the same rater at each visit, whenever possible. Any DU that developed over a previously healed ulcer was recorded as a new DU. Numbers of patients with no new DU at Week 16 are imputed using the last observation carried forward method.

Outcome measures

Outcome measures
Measure	Macitentan 3mg n=84 Participants Patients received macitentan once daily at a dose of 3 mg.	Macitentan 10mg n=84 Participants Patients received macitentan once daily at a dose of 10 mg.	Placebo n=87 Participants Patients received placebo once daily.
Percentage of Participants Without a New DU up to Week 16	56.0 Percentage of participants	54.8 Percentage of participants	59.8 Percentage of participants

SECONDARY outcome

Timeframe: Up to 95 weeks

Population: Modified intention to treat set. Ten patients were excluded from the modified intent to treat set due to protocol violations.

DU complications were defined as any one of the following: resulting from DU worsening: critical ischemic crisis necessitating hospitalization; gangrene, (auto)amputation; failure of conservative management; surgical and chemical sympathectomy, vascular reconstructions, or any unplanned surgery in the management of hand SSc manifestations; use of parenteral prostanoids; use of endothelin-receptor antagonists; class II, III, or IV narcotics or a \> 50% increase in the existing dose compared with baseline; initiation of systemic antibiotics for the treatment of infection attributed to DUs.

Outcome measures

Outcome measures
Measure	Macitentan 3mg n=84 Participants Patients received macitentan once daily at a dose of 3 mg.	Macitentan 10mg n=84 Participants Patients received macitentan once daily at a dose of 10 mg.	Placebo n=87 Participants Patients received placebo once daily.
Percentage of Participants With at Least One DU Complication	21.4 Percentage of participants	19.0 Percentage of participants	18.4 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Modified intention to treat set. Ten patients were excluded from the modified intent to treat set due to protocol violations.

HAQ-DI assesses functional ability regarding fine movements of the upper extremities, locomotor activities in the lower extremities, and movements of the upper and lower limbs. Responses were extracted from the Scleroderma Health Assessment Questionnaire covering 8 domains of functional disability (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other daily activities). A mean score ranging from 0-3 was calculated for each domain, and a composite score by dividing the summed domain scores by the number of domains. The composite score was interpreted as 0 (no impairment in function) to 3 (maximal impairment of function). Hand functionality was assessed using a composite of 4 domains (dressing and grooming, grip, hygiene, and eating).

Outcome measures

Outcome measures
Measure	Macitentan 3mg n=84 Participants Patients received macitentan once daily at a dose of 3 mg.	Macitentan 10mg n=84 Participants Patients received macitentan once daily at a dose of 10 mg.	Placebo n=87 Participants Patients received placebo once daily.
Change in Hand Functionality Health Assessment Questionnaire - Disability Index (HAQ-DI) Hand Component From Baseline to Week 16 Week 16	1.2 Units on a scale Standard Deviation 0.75	1.1 Units on a scale Standard Deviation 0.76	1.3 Units on a scale Standard Deviation 0.77
Change in Hand Functionality Health Assessment Questionnaire - Disability Index (HAQ-DI) Hand Component From Baseline to Week 16 Baseline	1.4 Units on a scale Standard Deviation 0.73	1.3 Units on a scale Standard Deviation 0.70	1.4 Units on a scale Standard Deviation 0.72

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Modified intention to treat set. Ten patients were excluded from the modified intent to treat set due to protocol violations.

Outcome measures

Outcome measures
Measure	Macitentan 3mg n=84 Participants Patients received macitentan once daily at a dose of 3 mg.	Macitentan 10mg n=84 Participants Patients received macitentan once daily at a dose of 10 mg.	Placebo n=87 Participants Patients received placebo once daily.
Health Assessment Questionnaire - Disability Index (HAQ-DI) Overall Score From Baseline to Week 16 Baseline	1.2 Units on a scale Standard Deviation 0.67	1.1 Units on a scale Standard Deviation 0.65	1.2 Units on a scale Standard Deviation 0.66
Health Assessment Questionnaire - Disability Index (HAQ-DI) Overall Score From Baseline to Week 16 Week 16	1.1 Units on a scale Standard Deviation 0.70	1.0 Units on a scale Standard Deviation 0.71	1.2 Units on a scale Standard Deviation 0.68

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Modified intention to treat set. Ten patients were excluded from the modified intent to treat set due to protocol violations.

Patients were asked to answer 24 questions on the use of the hand(s) affected by DUs over the past 7 days on a 6-point scale from 0 (yes without difficulty) to 5 (impossible). The HDISS-DU score is the arithmetic mean of the valid non-missing items. The scores are interpreted as 1 (better ability in completing activities) to 6 (worst ability in completing activities)

Outcome measures

Outcome measures
Measure	Macitentan 3mg n=84 Participants Patients received macitentan once daily at a dose of 3 mg.	Macitentan 10mg n=84 Participants Patients received macitentan once daily at a dose of 10 mg.	Placebo n=87 Participants Patients received placebo once daily.
Change in Hand Functionality - Hand Disability in Systemic Sclerosis - Digital Ulcers (HDISS-DU) Score From Baseline to Week 16 Baseline	3.0 Units on a scale Standard Deviation 1.08	2.9 Units on a scale Standard Deviation 1.05	2.9 Units on a scale Standard Deviation 1.14
Change in Hand Functionality - Hand Disability in Systemic Sclerosis - Digital Ulcers (HDISS-DU) Score From Baseline to Week 16 Week 16	2.8 Units on a scale Standard Deviation 1.17	2.7 Units on a scale Standard Deviation 1.11	2.9 Units on a scale Standard Deviation 1.12

Adverse Events

Macitentan 3mg

Serious events: 10 serious events

Other events: 73 other events

Deaths: 0 deaths

Macitentan 10mg

Serious events: 21 serious events

Other events: 73 other events

Deaths: 0 deaths

Placebo

Serious events: 13 serious events

Other events: 70 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Angelina Marr

Actelion Pharmaceuticals Ltd

Phone: +41 61 565 63 69

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Macitentan 3mg n=88 participants at risk Patients received macitentan once daily at a dose of 3 mg.	Macitentan 10mg n=87 participants at risk Patients received macitentan once daily at a dose of 10 mg.	Placebo n=89 participants at risk Patients received placebo once daily.
Nervous system disorders HEADACHE	19.3% 17/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	17.2% 15/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	21.3% 19/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
General disorders OEDEMA PERIPHERAL	11.4% 10/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	16.1% 14/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	4.5% 4/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Gastrointestinal disorders DIARRHOEA	11.4% 10/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	11.5% 10/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	6.7% 6/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Infections and infestations NASOPHARYNGITIS	8.0% 7/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	11.5% 10/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	5.6% 5/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Blood and lymphatic system disorders ANAEMIA	6.8% 6/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	11.5% 10/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	5.6% 5/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Infections and infestations INFECTED SKIN ULCER	17.0% 15/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	10.3% 9/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	14.6% 13/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	9.1% 8/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	10.3% 9/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	14.6% 13/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Skin and subcutaneous tissue disorders SKIN ULCER	15.9% 14/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	9.2% 8/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	10.1% 9/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	12.5% 11/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	9.2% 8/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	6.7% 6/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Nervous system disorders DIZZINESS	5.7% 5/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	8.0% 7/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	3.4% 3/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
General disorders FATIGUE	2.3% 2/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	8.0% 7/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	4.5% 4/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Gastrointestinal disorders NAUSEA	4.5% 4/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	5.7% 5/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	2.2% 2/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Infections and infestations INFLUENZA	2.3% 2/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	5.7% 5/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	3.4% 3/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Musculoskeletal and connective tissue disorders MYALGIA	5.7% 5/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	4.6% 4/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	3.4% 3/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Musculoskeletal and connective tissue disorders ARTHRALGIA	8.0% 7/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	3.4% 3/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	4.5% 4/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Investigations ALANINE AMINOTRANSFERASE INCREASED	5.7% 5/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	3.4% 3/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	2.2% 2/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Gastrointestinal disorders DYSPEPSIA	1.1% 1/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	3.4% 3/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	6.7% 6/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Musculoskeletal and connective tissue disorders BACK PAIN	9.1% 8/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	2.3% 2/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	6.7% 6/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Gastrointestinal disorders CONSTIPATION	8.0% 7/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	2.3% 2/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	3.4% 3/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	5.7% 5/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	2.3% 2/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	1.1% 1/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Skin and subcutaneous tissue disorders DERMATITIS	5.7% 5/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	2.3% 2/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	1.1% 1/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Musculoskeletal and connective tissue disorders BURSITIS	2.3% 2/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	2.3% 2/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	5.6% 5/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	3.4% 3/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	1.1% 1/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	6.7% 6/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients
Infections and infestations PHARYNGITIS	5.7% 5/88 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	0.00% 0/87 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients	0.00% 0/89 • Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation Safety set - all treated patients