Bosentan in Digital Ulcers - Full Text View

Purpose

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).

Condition	Intervention	Phase
Systemic Sclerosis Digital Ulcers	Drug: bosentan	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Long-term Bosentan Open Label Extension of the AC-052-331 Study in Systemic Sclerosis Patients With Ischemic Digital Ulcers

Resource links provided by NLM:

Genetics Home Reference related topics: systemic scleroderma

MedlinePlus related topics: Scleroderma

Drug Information available for: Bosentan

U.S. FDA Resources

Further study details as provided by Actelion:

Primary Outcome Measures:

Total Number of New Digital Ulcers (DUs) Per Patient Observed by the Investigator at Planned Visits [ Time Frame: At planned visits up to week 80 ] [ Designated as safety issue: No ]
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
Time to Complete Healing of Each Baseline DU [ Time Frame: Baseline to healing ] [ Designated as safety issue: No ]
Time to Complete Healing of Each New DU [ Time Frame: New DU occurence to healing ] [ Designated as safety issue: No ]
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Dressing [ Time Frame: 80 weeks ] [ Designated as safety issue: No ]
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.
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Arising [ Time Frame: 80 weeks ] [ Designated as safety issue: No ]
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.
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Eating [ Time Frame: 80 weeks ] [ Designated as safety issue: No ]
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.
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Walking [ Time Frame: 80 weeks ] [ Designated as safety issue: No ]
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.
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Hygiene [ Time Frame: 80 weeks ] [ Designated as safety issue: No ]
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.
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Reach [ Time Frame: 80 weeks ] [ Designated as safety issue: No ]
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.
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Grip [ Time Frame: 80 weeks ] [ Designated as safety issue: No ]
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.
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Activity [ Time Frame: 80 weeks ] [ Designated as safety issue: No ]
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.
Mean Changes From Baseline at Each 16 Week Interval up to Week 80 in Overall Hand Pain Related to Finger Ulcers [ Time Frame: 80 weeks ] [ Designated as safety issue: No ]
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.
Mean Change From Baseline at Each 16 Week Interval up to Week 80 in the UK Systemic Sclerosis Functional Score (UKFS) [ Time Frame: 80 weeks ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Adverse Events up to 24 Hours After Last Study Medication [ Time Frame: 80 weeks ] [ Designated as safety issue: Yes ]
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.
Serious Adverse Events up to 28 Days After Last Study Medication [ Time Frame: 80 weeks ] [ Designated as safety issue: Yes ]
Number of patients with at least one treatment-emergent serious adverse event. Adverse events that occurred after study drug initiation and up to 28 days after study drug discontinuation.
Adverse Events Leading to Permanent Discontinuation of the Study Medication [ Time Frame: 80 weeks ] [ Designated as safety issue: Yes ]
Number of patients with an adverse event leading to permanent discontinuation of the study treatment

Enrollment:	116
Study Start Date:	July 2004
Study Completion Date:	October 2008
Primary Completion Date:	October 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Drug: bosentan Initial dose: bosentan 62.5 mg tablets b.i.d. for 4 weeks Maintenance dose: bosentan 125 mg tablets b.i.d.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

· Patients with SSc according to the classification criteria of the American College of Rheumatology
- SSc patients with at least one DU at baseline qualifying as a CU (see definition section 3.2.2)
- 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.
- Male or female patients >/= 18 years of age
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.
Women not of childbearing potential are defined as postmenopausal (i.e., amenorrhea for at least 1 year), or surgically or naturally sterile.
- Signed informed consent

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00319696

Show 38 Study Locations

Sponsors and Collaborators

Actelion

More Information

No publications provided

Responsible Party:	Actelion
ClinicalTrials.gov Identifier:	NCT00319696 History of Changes
Other Study ID Numbers:	AC-052-333, RAPIDS-2 OL
Study First Received:	April 27, 2006
Results First Received:	June 29, 2012
Last Updated:	September 27, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Actelion:

systemic sclerosis
digital ulcers
bosentan
open label
finger ulcers

Additional relevant MeSH terms:

Scleroderma, Systemic
Scleroderma, Diffuse
Sclerosis
Ulcer
Connective Tissue Diseases
Skin Diseases

Pathologic Processes
Bosentan
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013

Bosentan in Digital Ulcers (RAPIDS 2 OL)