Clinical Research Study With Clazosentan to Evaluate Its Effects on Preventing Complications Due to the Narrowing of the Blood Vessels (Vasospasm) in the Brain, Caused by Bleeding Onto the Surface of the Brain

Inclusion Criteria:

1. Written informed consent to participate in the study must be obtained from the subject
or proxy/legal representative at any time from hospital admission to prior to
initiation of any study-mandated procedure,

2. Males and females aged 18 to 70 years (inclusive, at hospital admission),

3. Subjects with a ruptured saccular aneurysm, angiographically confirmed by DSA or CTA,
which has been successfully secured within 72 hours of rupture, by surgical clipping
or endovascular coiling,

4. WFNS (World Federation of Neurosurgical Societies) grades 1-4 (based on Glasgow Coma
Scale [GCS]) assessed after recovery from the aneurysm-securing procedure and after
external ventricular drainage for hydrocephalus, if required,

5. Subjects must meet one of the two following inclusion criteria:

A) High-risk prevention: Subjects with a "thick and diffuse clot" (thick and diffuse
is defined as a thick confluent clot, more than 4 mm in thickness, involving 3 or more
basal cisterns) on the hospital admission CT scan, absence of cerebral vasospasm at
the time of randomization, and possibility to start study drug in the ICU (or
equivalent environment where all protocol assessments can be performed and the Patient
Management Guidelines followed), within 96 hours after the time of the aneurysm
rupture,

OR

B) Early treatment: Subjects without a thick and diffuse clot on the hospital
admission CT scan who develop asymptomatic or minimally symptomatic moderate to severe
angiographic vasospasm, within the 14-day period post-aneurysm rupture, and for whom
it is possible to start study drug in the ICU (or equivalent environment where all
protocol assessments can be performed and the Patient Management Guidelines followed),
within 24 hours of this angiographic diagnosis,

6. Presence of a cerebral CT scan, performed at least 8 hours postaneurysm-securing
procedure and within 24 hours prior to randomization, which rules out a significant
(e.g., symptomatic) new or worsened cerebral infarct or re-bleeding of the repaired
aneurysm,

7. A woman of childbearing potential is eligible only if the pregnancy test performed
during the screening period is negative.

Exclusion Criteria:

aSAH, aneurysm-securing procedure, vasospasm:

1. Subjects with SAH due to causes other than a saccular aneurysm (e.g., trauma or
rupture of fusiform or mycotic aneurysms, SAH associated with arterio-venous
malformation, vertebral dissections),

2. Significant bleeding post aneurysm-securing procedure (e.g., due to intra-ventricular
drain, intra-cerebral hemorrhage, epidural hematoma, vessel dissection or rupture,
re-bleeding of the repaired aneurysm), based on investigator judgment,

3. Intra-or peri-aneurysm securing procedure complication requiring non-routine medical
or interventional treatment such as administration of an antithrombotic or
anti-platelet agent (e.g., abciximab), which is not completely resolved prior to
randomization,

4. Intraventricular hemorrhage on the hospital admission CT scan, filling more than 50%
of both lateral ventricles and with involvement of the 3rd and 4th ventricles.

5. Intracerebral hemorrhage on the hospital admission CT scan, with an approximate volume
of > 50 mL,

6. Presence of cerebral vasospasm at hospital admission (initial admission or transfer
from another hospital) believed to be associated with a prior bleed (i.e., occurring
before the bleed for which the subject is currently hospitalized). Vasospasm occurring
during the aneurysm securing procedure is not an exclusion criterion,

Neurological and functional status:

7. Subjects with a new major neurological deficit occurring post aneurysm-securing
procedure which is attributable to the procedure and does not improve to pre-procedure
status before randomization,

8. Subjects with a GCS score of ≤ 9 at the time of randomization and without intracranial
pressure (ICP) monitoring,

9. Modified Rankin Score of 3 or higher, prior to the aSAH (i.e., due to a chronic
condition),

Other clinical considerations:

10. Subjects with total bilirubin > 2 times the upper limit of normal, and/or a known
diagnosis or clinical suspicion of liver cirrhosis or moderate to severe hepatic
impairment,

11. Hypotension (systolic blood pressure [SBP] ≤ 90 mmHg) at time of randomization that is
refractory to treatment,

12. Unresolved pulmonary edema or significant pneumonia still present at the time of
randomization, or severe hypoxia at the time of randomization in intubated subjects,
defined as PaO2/FiO2 ≤ 200,

13. High sustained ICP (> 25 mmHg lasting > 20 minutes) at time of randomization, despite
optimal treatment, in subjects with ICP monitoring,

14. Severe cardiac failure requiring inotropic support at the time of randomization.