Clazosentan in Preventing the Occurrence of Cerebral Vasospasm Following an Aneurysmal Subarachnoid Hemorrhage (aSAH)

Inclusion criteria:

1. Male or female patients aged 18 to 70 years (inclusive) or male patients aged 45 to 70
(inclusive) or males aged 18 to 44 (inclusive) who are surgically or naturally sterile
or can personally sign the core Informed Consent

2. Patients with a ruptured saccular aneurysm that has been confirmed by digital
subtraction angiography (DSA) and for which clipping or coiling (endovascular
obliteration) is possible.

3. Patients with a diffuse or localized thick subarachnoid clot on baseline CT scan.
Measurements defining clot thickness and extension are as follows: Diffuse: Clot with
long axis >= 20 mm, or any clot if present in both hemispheres Localized: Clot with
long axis < 20 mm Thick: Clot with short axis >= 4 mm Thin: Clot with short axis < 4
mm

4. Start of screening within 48 hours post onset of aSAH clinical symptoms

5. World Federation of Neurological Surgeons (WFNS) Grades I-IV, and those Grade V
patients who improve to Grade IV or less after ventriculostomy

6. In the case of multiple aneurysms, the aneurysm that has ruptured is identified with a
high likelihood during the screening period

7. Women of childbearing potential with pre-treatment negative serum pregnancy test

8. Patient is able to start the study drug infusion within 56 hours after the rupture of
the aneurysm, and the procedure option (clipping or coiling) must either be started
within a maximum of 12 hours after the start of study drug infusion or should have
been already performed

9. Written informed consent to participate in the study must be obtained from the patient
or a legal representative prior to initiation of any study-related procedure and
enrollment

Exclusion criteria:

1. Patients with SAH due to other causes (e.g., trauma or rupture of fusiform or mycotic
aneurysms)

2. Patients with intraventricular or intracerebral blood, in the absence of subarachnoid
blood

3. No visualized clot or presence of only localized thin clot on CT (< 20 mm x 4 mm)

4. Presence of any degree of cerebral vasospasm on screening angiogram

5. Patients with hypotension (systolic blood pressure (SBP) <=90 mmHg) refractory to
fluid therapy

6. Patients with neurogenic pulmonary edema or severe cardiac failure requiring inotropic
support

7. Any severe or unstable concomitant condition or disease (e.g., known significant
neurological deficit, cancer, hematological, or coronary disease), or chronic
condition (e.g., psychiatric disorder) which, in the opinion of the Investigator,
would affect the assessment of the safety or efficacy of the study drug

8. Advanced kidney and/or liver disease, as defined by plasma creatinine >=2 mg/dl (177
micromol/l) and/or total bilirubin > 3 mg/dl (51.3 micromol/l)

9. Any known or CT evidence of previous major cerebral damage (e.g., stroke [> 2 cm],
traumatic brain injury [> 2 cm], previously treated cerebral aneurysm, arterial venous
malformation [AVM]), or other preexisting cerebrovascular disorders, which may affect
accurate diagnosis and evaluation of SAH

10. Patients receiving prophylactic i.v. nimodipine or i.v. nicardipine. If present, these
must be stopped at least 4 hours prior to initiation of the study treatment

11. Patients who have received thrombolytics, including intracisternal administration,
intrathecal treatments and therapeutic hypothermia for treatment of the SAH

12. Patients who have received an investigational product within 28 days prior to
randomization

13. Patients with current alcohol or drug abuse or dependence