Pulmonary Arterial Hypertension
Conditions
Keywords
bosentan, PAH related to Eisenmenger physiology, Tracleer
Brief summary
This 6-month open label study will evaluate the long term safety of bosentan (via oxygen saturation) and efficacy (exercise capacity) in patients who have completed the BREATHE-5 study (PAH related to Eisenmenger physiology). Treatment duration is 6 months.
Detailed description
This is a multicenter, open-label, single -arm study with bosentan, initial dose of 62.5 mg b.i.d., with a target dose of 125 mg b.i.d. All patients will be assessed for eligibility during the baseline visit (same as Week 16, end of study BREATHE-5 visit), and will have the option to enter into the open-label extension study at a starting dose of 62.5 mg b.i.d., for safety reasons. Visit 2 is required as a safety visit to assess oxygen saturation (SpO2) after 1 week of bosentan treatment. Patients will return for Visit 4 after 4 weeks of treatment, and the dose will be up-titrated to 125 mg b.i.d. or maintained at 62.5 mg b.i.d. at the judgement of the investigator. Data will be collected for a total of 24 weeks or until the sponsor decides to stop the study. If the results from Study AC-052-403 or AC-052-405 demonstrate significant safety issues, this extension study may be terminated at the sponsor's request.
Interventions
DRUGTracleer®
Patients will receive up to 125 mg b.i.d. of Tracleer.
Sponsors
Actelion
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients stable with PAH upon completion of the BREATHE-5 randomized, double-blind, placebo- controlled 16-week study. 2. For female patients, only non-pregnant women who are surgically sterile, postmenopausal or have documented infertility (over 50 years of age and amenorrheic for at least 1 year), or those of childbearing potential using one of the following methods of contraception: Barrier-type devices (e.g., condom, diaphragm) used ONLY in combination with a spermicide. A double-barrier method is recommended; intrauterine devices (IUDs); oral or implanted contraceptives, if used in combination with a barrier method. 3. Patients providing written informed consent.
Exclusion criteria
1. Patients who withdrew prematurely from BREATHE-5, AC-052-405. 2. Patients who are pregnant or nursing. 3. Patients who are receiving epoprostenol or prostacyclin analogues, or are expected to receive any of these drugs during the study. 4. Patients with AST and/or ALT values greater than 3 times the upper limit of normal. 5. Patients with hemoglobin or hematocrit that is more than 30% below the normal range (patients with secondary polycythemia are permitted in the study). 6. Patients with systolic blood pressure \< 85 mm Hg. 7. Patients taking phosphodiesterase inhibitors, other endothelin receptor antagonists or are receiving another investigational product. 8. Patients active on organ transplant list. 9. Patients who are receiving or expected to receive glyburide, cyclosporin A or tacrolimus. 10. Patients not able to comply with the protocol or adhere to therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 6-minute Walk Distance | from baseline to week 24 | — |
| Change in Borg Dyspnea Index | from baseline to week 24 | Borg scale a numerical scale for assessing dyspnea, from 0 representing no dyspnea to 10 as maximal dyspnea. |
| Number of Participants With a Change in WHO Functional Class | from baseline to week 24 | Number of participants with a change in WHO functional class from baseline to week 24. A change from a higher to a lower functional class (i.e. III to II, III to I or II to I) is considered as an improvement. |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Participant flow
Recruitment details
Eight centers in six countries: Germany (1), Italy (2), the Netherlands (1), Spain (1), U.K. (2), U.S.A. (1) Patients with stable PAH upon completion of the BREATHE-5 randomized, double-blind, placebocontrolled 16-week study were given option to enter into the open-label extension study.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Arm | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Overall Study Arm |
|---|---|
| Age, Continuous | 39.8 Years STANDARD_DEVIATION 11.8 |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 25 / 37 |
| serious Total, serious adverse events | 7 / 37 |
Outcome results
Primary
Change in 6-minute Walk Distance
Time frame: from baseline to week 24
Population: The analysis was done in the safety set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Study Arm | Change in 6-minute Walk Distance | 13.5 m | Standard Deviation 57.2 |
Primary
Change in Borg Dyspnea Index
Borg scale a numerical scale for assessing dyspnea, from 0 representing no dyspnea to 10 as maximal dyspnea.
Time frame: from baseline to week 24
Population: The analysis was done in the safety set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Study Arm | Change in Borg Dyspnea Index | 0.1 units on a scale | Standard Deviation 1.4 |
Primary
Number of Participants With a Change in WHO Functional Class
Number of participants with a change in WHO functional class from baseline to week 24. A change from a higher to a lower functional class (i.e. III to II, III to I or II to I) is considered as an improvement.
Time frame: from baseline to week 24
Population: The analysis was done in the safety set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Overall Study Arm | Number of Participants With a Change in WHO Functional Class | 13 participants |