Bosentan in Digital Ulcers

Digital Ulcers Clinical Trial

— RAPIDS 2 OL  

Official title:

Long-term Bosentan Open Label Extension of the AC-052-331 Study in Systemic Sclerosis Patients With Ischemic Digital Ulcers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00319696
• Other study ID #: AC-052-333
• Status: Completed
• Phase: Phase 3
• Start date: July 8, 2004
• Est. completion date: January 22, 2009

Study information

• Verified date: December 2018
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: January 22, 2009
• Est. primary completion date: January 22, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Digital Ulcers
• Skin Ulcer
• Ulcer

Intervention

Drug:
• Bosentan 62.5 mg
Bosentan 62.5-mg oral tablets twice daily (b.i.d.) for 4 weeks (initial dose)
• Bosentan 125 mg
Bosentan 125-mg oral tablets administered b.i.d. (target dose)

Locations

Country	Name	City	State
Austria	Universitatsklinik	Innsbruck
Austria	AKH Universitatsklinik	Wien
Canada	Janet Pope, MD	London	Ontario
Canada	Eric Rich, MD	Montreal	Quebec
Canada	Murray Baron, MD	Montreal	Quebec
Canada	Peter Lee, MD	Toronto	Ontario
France	Centre Hospitalier Universitaire	Grenoble
France	CHRU Claude Huriez	Lille
Germany	Universitatsklinikum	Dresden
Germany	Universitatsklinikum	Erlangen
Germany	Universitatsklinik	Freiburg
Germany	Universitatsklinik	Koln
Italy	Instituto di Clinica, Villa Monna Tessa	Firenze
Italy	Ospedale Maggiore	Milano
Italy	Policlinico Umberto 1	Roma
Switzerland	Inselspital, Universitatspital Bern	Bern
United Kingdom	Selly Oak Hospital	Birmingham
United Kingdom	Royal Free Hospital	London
United Kingdom	Freeman Hospital	Newcastle
United States	David Collier, MD	Aurora	Colorado
United States	Frederick Wigley, MD	Baltimore	Maryland
United States	Barri Fessler, MD	Birmingham	Alabama
United States	Peter Merkel, MD	Boston	Massachusetts
United States	Edwin Smith, MD	Charleston	South Carolina
United States	Medical Universtiy of South Carolina	Charleston	South Carolina
United States	Nadera Sweiss, MD	Chicago	Illinois
United States	Naomi Rothfield, MD	Farmington	Connecticut
United States	Maureen Mayes, MD	Houston	Texas
United States	Daniel Furst, MD	Los Angeles	California
United States	Avram Goldberg, MD	Manhasset	New York
United States	Mary Ellen Csuka, MD	Milwaukee	Wisconsin
United States	Vivien Hsu, MD - UMDNJ	New Brunswick	New Jersey
United States	Mittie Doyle, MD	New Orleans	Louisiana
United States	Thomas Medsger, MD	Pittsburgh	Pennsylvania
United States	Thomas Osborn, MD	Rochester	Minnesota
United States	Jerry Molitor, MD	Seattle	Washington
United States	Howard Kenney, MD	Spokane	Washington
United States	Bashar Kahaleh, MD	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

United States,  Austria,  Canada,  France,  Germany,  Italy,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Complete Healing of Each Baseline DU		Baseline to healing
Primary	Time to Complete Healing of Each New DU		New DU occurence to healing
Primary	Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Dressing	SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.	80 weeks
Primary	Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Arising	SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.	80 weeks
Primary	Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Eating	SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.	80 weeks
Primary	Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Walking	SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.	80 weeks
Primary	Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Hygiene	SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.	80 weeks
Primary	Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Reach	SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.	80 weeks
Primary	Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Grip	SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.	80 weeks
Primary	Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Activity	SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.	80 weeks
Primary	Mean Changes From Baseline at Each 16 Week Interval up to Week 80 in Overall Hand Pain Related to Finger Ulcers	Overall hand pain related to finger ulcers was assessed by the patient using a Visual Analogue Scale. Patients were instructed to score their pain by marking on the continuous 10-cm scale, where 0 (left) was no pain and 100 (right) very severe pain, in response to the question, "How much pain have you had because of your finger ulcers in the past week?" The investigator measured the distance in millimeters between 0 and the patient mark with the ruler provided and recorded the distance.	80 weeks
Primary	Mean Change From Baseline at Each 16 Week Interval up to Week 80 in the UK Systemic Sclerosis Functional Score (UKFS)	UKFS relates to upper and lower extremity function and muscle weakness. For each item, the patient indicated the responses that best described their current ability: "able to perform in a normal manner," "able to perform with alteration in style," "can only manage with difficulty," and "impossible to achieve." Each response was given an integer from 0 (able to perform in a normal manner) to 3 (impossible to achieve), and the sum of individual responses provided an overall score of 0 to 33. Missing values were replaced with the worst value the patient reported on the other items at that visit.	80 weeks
Primary	Total Number of New Digital Ulcers (DUs) Per Patient Observed by the Investigator at Planned Visits	The total number of new DUs per patient observed by the investigator at planned visits and new transient DUs recorded in the patient diary (a patient diary was used to record DUs that might appear and disappear between two planned visits) were assessed at each clinic visit	At planned visits up to week 80
Secondary	Adverse Events up to 24 Hours After Last Study Medication	Number of patients with at least one treatment-emergent adverse event. All adverse events that occurred after study drug initiation and up to 24 hours after study drug discontinuation were to be recorded.	80 weeks
Secondary	Adverse Events Leading to Permanent Discontinuation of the Study Medication	Number of patients with an adverse event leading to permanent discontinuation of the study treatment	80 weeks
Secondary	Serious Adverse Events up to 28 Days After Last Study Medication	Number of patients with at least one treatment-emergent serious adverse event (TESAE) were reported. TESAEs are serious AEs that occurred after study drug initiation and up to 28 days after study drug discontinuation. More details on the SAEs are provided in the specific Adverse Events Section	80 weeks