A PHASE 3, MULTI-CENTER, OPEN LABEL STUDY TO EVALUATE THE LONG-TERM SAFETY OF MONOTHERAPY SITAXSENTAN SODIUM AND COMBINATION THERAPY WITH SITAXSENTAN SODIUM AND SILDENAFIL CITRATE IN SUBJECTS WITH PULMONARY ARTERIAL HYPERTENSION

• Register: EUCTR
• Last refreshed on: 12 December 2016
• Main ID: EUCTR2008-005886-78-CZ
• Date of registration: 10/12/2008
• Prospective Registration: Yes
• Primary sponsor: Pfizer Ltd.
• Public title: A PHASE 3, MULTI-CENTER, OPEN LABEL STUDY TO EVALUATE THE LONG-TERM SAFETY OF MONOTHERAPY SITAXSENTAN SODIUM AND COMBINATION THERAPY WITH SITAXSENTAN SODIUM AND SILDENAFIL CITRATE IN SUBJECTS WITH PULMONARY ARTERIAL HYPERTENSION
• Scientific title: A PHASE 3, MULTI-CENTER, OPEN LABEL STUDY TO EVALUATE THE LONG-TERM SAFETY OF MONOTHERAPY SITAXSENTAN SODIUM AND COMBINATION THERAPY WITH SITAXSENTAN SODIUM AND SILDENAFIL CITRATE IN SUBJECTS WITH PULMONARY ARTERIAL HYPERTENSION
• Date of first enrolment: 12/01/2010
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-005886-78
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Czech Republic

Key inclusion & exclusion criteria

Inclusion criteria:
1.One of the following scenarios must be applicable:
•Previously enrolled in B1321001 for at least 4 weeks, was discontinued from the study after the Adjudication Committee granted discontinuation based on early escape or the need to add or increase the dose of a chronic medication for worsening PAH, or
•Previously enrolled in B1321003, discontinued from the study after the Adjudication Committee granted Early Discontinuation due to the need to add or increase the dose of a chronic medication for worsening PAH, or
•Completed B1321001 but unable to enroll in B1321003 or completed B1321003 study as planned
2.Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
3.Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
4.If on any medication belonging to the statin drug class (eg, lovastatin, atorvastatin), was receiving a stable dose for at least 3 months prior to the time of the first Screening day for B1321001 and was maintained throughout the study.
5.Women of childbearing potential must be using 2 forms of medically acceptable contraception (at least 1 barrier method), have a negative pregnancy test at Baseline/Day 1 and agree to use reliable methods of contraception for at least 1 month after the final study visit. Women who are surgically sterile or those who are post-menopausal for at least 2 years are not considered to be of childbearing potential.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.Treated with an investigational drug (other than sitaxsentan or sildenafil in either B1321001 or B1321003) or device that has not received regulatory approval within the 30 days prior to Baseline/Day 1 or during the study.
2.Is taking, or has an anticipated need for systemic administration (oral, intravenous (IV)) of cyclosporine A for the duration of the study.
3.Is using chronic arginine supplementation including HeartBar®. This must have been stopped for at least 30 days prior to the first Screening day for B1321001.
4.Has uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure >160 mm Hg or sitting diastolic blood pressure >100 mm Hg at Baseline/Day 1.
5.Has hypotension defined as systolic arterial pressure <90 mm Hg after sitting for 5 minutes at Baseline/Day 1.
6.Has a history of portal hypertension or chronic liver disease, including hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication) defined as mild to severe hepatic impairment (Child-Pugh Class A-C).
7.Has hepatic dysfunction, defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ?1.5 times the upper limit of the normal (ULN) range or bilirubin >2 times the ULN range at Baseline/Day 1.
8.Was discontinued from B1321003 due to AST or ALT >3 times upper limit of normal and a direct bilirubin >2 times the upper limit of normal; or AST or ALT >5 times the upper limit of normal.
9.Has chronic renal insufficiency as defined by serum creatinine >2.5 mg/dL at first screening day for B1321001 or requires dialytic support.
10.Has a hemoglobin concentration <10 g/dL at Baseline/Day 1.
11.History of obstructive sleep apnea (treated or untreated).
12.History of atrial septostomy.
13.Has known hereditary degenerative retinal disorders (such as retinitis pigmentosa) or history of non-arteritic anterior ischaemic optic neuropathy.
14.Has untreated proliferative diabetic retinopathy.
15.Other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
16.Has a psychiatric, addictive or other disorder that compromises the ability to give informed consent for participating in this study. This includes subjects with a recent history of abusing alcohol or illicit drugs 30 days prior to the time of the first screening day for B1321001 and for the duration of the study.
17.Is currently pregnant or breastfeeding or intends to become pregnant during the duration of the study.
18.Investigators, study staff or their immediate families.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

PULMONARY ARTERIAL HYPERTENSION
MedDRA version: 9.1 Level: HLT Classification code 10037401 Term: Pulmonary hypertensions

Intervention(s)

Trade Name: Thelin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Sitaxsentan Sodium
CAS Number: 210421-64-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Revatio
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Sildenafil citrate
CAS Number: 139755-83-2
Current Sponsor code: UK-92,480
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Main Objective: The primary objective of this study is to evaluate the long-term safety of sitaxsentan and sitaxsentan plus sildenafil in subjects with PAH who are eligible for this study if B1321003 (combination therapy study) was completed or if early escape was met in B1321001 (placebo controlled study) or early discontinuation in B1321003.

Secondary Objective: The secondary objective of this study is to evaluate the efficacy of sitaxsentan and sitaxsentan plus sildenafil in subjects with PAH who are eligible for this study if B1321003 was completed or if early escape was met in B1321001 or early discontinuation in B1321003 by determining change from Baseline/Day 1 to Weeks 12 and 24 in 6-minute walk distance (6MWD).

Primary end point(s): No endpoints.

Secondary ID(s)

B1321002