Clinical trial NCT00319696: Bosentan in Digital Ulcers
Official title: Long-term Bosentan Open Label Extension of the AC-052-331 Study in Systemic Sclerosis Patients With Ischemic Digital Ulcers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Digital Ulcers
Keywords: digital ulcers
systemic sclerosis
finger ulcers
bosentan
open label
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2006-04-27
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of the study is to collect long-term efficacy, tolerability and safety data of bosentan in Systemic Sclerosis (SSc) patients suffering from ischemic digital ulcers (DUs).


Eligibility criteria: Inclusion Criteria:

1. Patients with SSc according to the classification criteria of the American College of Rheumatology
2. SSc patients with at least one DU at baseline qualifying as a CU (see definition section 3.2.2)
3. CU occurred \< 3 months and \> 1 week prior to randomization. The subset of patients with SSc felt to be at high risk for DUs will be identified in the screening period but will not be eligible for enrollment until a CU has developed
4. Male or female patients \>/= 18 years of age
5. Women of childbearing potential must have a negative pre-treatment pregnancy test and use a reliable method of contraception during study treatment and for at least 3 months after study treatment termination
6. Women not of childbearing potential are defined as postmenopausal (i.e., amenorrhea for at least 1 year), or surgically or naturally sterile
7. Signed informed consent.

Exclusion Criteria:

1. DUs due to condition other than SSc
2. Severe PAH (WHO class III and IV)
3. Systolic blood pressure \< 85 mmHg
4. Hemoglobin concentration \< 75% of the lower limit of the normal range
5. AST and/or ALT values greater than 3 times the upper limit of normal
6. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C
7. Severe malabsorption or any severe organ failure (e.g., lung, kidney) or any life-threatening condition
8. Pregnancy or breast-feeding
9. Previous treatment with bosentan
10. Treatment with any of the following: glibenclamide (glyburide), fluconazole, cyclosporine A, tacrolimus and any other calcineurin inhibitor 1 week prior to randomization
11. Local injection of botulinum toxin in an affected finger 1 month prior to randomization
12. Treatment with parenteral prostanoids (prostaglandin E, epoprostenol, treprostinil sodium or other prostacyclin analogs) 3 months prior to randomization
13. Treatment with inhaled or oral prostanoids one month prior to randomization
14. Systemic antibiotics to treat infection of DUs 2 weeks prior to randomization
15. Treatment with phosphodiesterase inhibitors such as sildenafil, except for intermittent treatment of male erectile dysfunction
16. Body weight \< 40 kg
17. Patient with conditions that prevent compliance with the protocol or adhering to therapy
18. Patient who received an investigational product within 1 month preceding screening
19. Known hypersensitivity to bosentan or any of the excipients.

Primary outcomes:
measure: Time to Complete Healing of Each Baseline DU
timeFrame: Baseline to healing
measure: Time to Complete Healing of Each New DU
timeFrame: New DU occurence to healing
measure: Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Dressing
timeFrame: 80 weeks
measure: Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Arising
timeFrame: 80 weeks
measure: Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Eating
timeFrame: 80 weeks
measure: Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Walking
timeFrame: 80 weeks
measure: Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Hygiene
timeFrame: 80 weeks
measure: Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Reach
timeFrame: 80 weeks
measure: Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Grip
timeFrame: 80 weeks
measure: Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Activity
timeFrame: 80 weeks
measure: Mean Changes From Baseline at Each 16 Week Interval up to Week 80 in Overall Hand Pain Related to Finger Ulcers
timeFrame: 80 weeks
measure: Mean Change From Baseline at Each 16 Week Interval up to Week 80 in the UK Systemic Sclerosis Functional Score (UKFS)
timeFrame: 80 weeks
measure: Total Number of New Digital Ulcers (DUs) Per Patient Observed by the Investigator at Planned Visits
timeFrame: At planned visits up to week 80
Secondary outcomes:
measure: Adverse Events up to 24 Hours After Last Study Medication
timeFrame: 80 weeks
measure: Adverse Events Leading to Permanent Discontinuation of the Study Medication
timeFrame: 80 weeks
measure: Serious Adverse Events up to 28 Days After Last Study Medication
timeFrame: 80 weeks
Other outcomes:
Locations:
Study officials:
References: