Long-Term, Open-Label, Multicenter, Extension Study of Bosentan in Patients With Pulmonary Hypertension Associated With Sickle Cell Disease Completing a Double-Blind ASSET Study (AC-052-368 or AC 052-369)
Long-Term, Open-Label, Multicenter, Extension Study of Bosentan in Patients With Pulmonary Hypertension Associated With Sickle Cell Disease Completing a Double-Blind ASSET Study (AC-052-368 or AC 052-369)
This study will assess the safety and efficacy of bosentan therapy (in a study known as ASSET) for patients who have high blood pressure in the lungs associated with sickle cell disease. That form of hypertension places people at risk for complications, including shortness of breath, pain, pneumonia, and death. Previous studies have shown that bosentan can be helpful in reducing pulmonary hypertension.
Patients ages 16 and older who have completed the 16-week treatment in the ASSET 1 or ASSET 2 study and who are not pregnant or breastfeeding may be eligible for this study. The research will be conducted in about 25 hospitals in the United States and Europe. Up to 30 participants will be enrolled. The screening visit will involve a physical examination, blood sample of about 3 teaspoons for laboratory tests, and a pregnancy test. Patients' doctors will give them bosentan tablets (62.5 mg each), to take one in the morning and one in the evening. After 1 month, patients will be told whether the dose should be increased to 125 mg tablets to take twice a day. Two weeks after the increase in dose, a blood test will be done to analyze the drug's effects on the liver. After the start of treatment, patients will return for visits every 6 months, when there will be a 6-minute walking test to measure exercise capacity and evaluate shortness of breath. There will be follow-up for patients up to the end of the study and for 28 days after the last dose of bosentan is taken, to collect information about side effects.
Some patients on bosentan have had changes in liver function and red blood cell count. Side effects commonly reported are headache, flushed appearance, inflammation of the throat and nasal passages, and gastrointestinal symptoms. If patients have sudden worsening in breathing in the first few weeks after taking bosentan, they should immediately tell their doctors, because it may be necessary to change the treatment.
The object of this study is to assess long-term safety, tolerability and efficacy of bosentan in patients with pulmonary hypertension (PH) associated with sickle cell disease (SCD). The study population will include male and female patients with sickle cell disease (SS,S-beta-Thalassemia) who have previously completed the 16-week treatment period of the double-blind study of bosentan (ASSET 1 or ASSET 2). Patients who meet all the inclusion criteria and none of the exclusion criteria will be started on 62.5 mg bid for 4 weeks and then start the maintenance dose of 125 mg bid (or stay on 62.5 mg if their weight is less than 40kg/90lbs). Patients will be divided into two groups. Group A will consist of patients who begin this study within 4 weeks of completing ASSET 1 or ASSET2. Group B will consist of patients who begin this study longer than 4 weeks after completing ASSET I or ASSET 2. Patients will remain on drug until the FDA approves the drug for use in patients with pulmonary hypertension or until the sponsor decides to stop the study.
Reliable methods of contraception are:
Hormone-based contraceptives alone, regardless of the route of administration, are not considered to be reliable methods of contraception.
Abstention, rhythm method, and contraception by the partner alone are not acceptable methods of contraception.
Women not of childbearing potential are defined as prepubescent, postmenopausal (i.e., amenorrhea for at least 1 year), or surgically or naturally sterile.
Signed written informed consent is obtained from the patient or patient's parent/ legal representative prior to initiation of any study-related procedure.
EXCLUSION CRITERIA
All patients (Groups A and B):
Any major protocol violation in the preceding double-blind ASSET study*.
Hemoglobin concentration less than 6.0 g/dL.
Pregnancy or breast-feeding.
* Protocol violations will be reviewed by the monitor during site visits and discussed with the study staff on an ongoing basis and at the patient's completion of the double-blind study.
Group B only:
Acute liver disease.
Newly diagnosed cirrhosis or portal hypertension.
ALT greater than or equal to 3 times ULN and/or albumin greater than 20% below LLN.
Newly diagnosed psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements.