Clinical trial NCT00728182 (phase 2, status: completed)
Conditions: stroke
ICD codes: G46.4, G46.3, Z82.3
Drugs: na-1, placebo
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria

          -  A diagnosis of a ruptured or unruptured brain aneurysm deemed suitable for repair by
             neuroendovascular techniques involving intraluminal occlusion by detachable platinum
             coils, stent-assisted coiling, pipeline stent, balloon-assisted coiling, covered stent
             only, neck-bridge device, re-coiling, or re-treatment of a previously coiled/treated
             aneurysm. There are no restrictions on adjunctive devices. For patients with a
             ruptured aneurysm, endovascular repair must take place within 72 hours of the ictal
             haemorrhage.

          -  If the aneurysm has ruptured, patient should be Grade I-III on the World Federation of
             Neurological Surgeons (WFNS) grading scale for subarachnoid hemorrhage. If the patient
             is intubated but alert and able to follow commands (at least a 2-step command), and is
             not kept intubated for neurological status (i.e., WFNS Grade IV or V), the patient is
             considered WFNS Grade III and is eligible for the trial.

          -  Absence of ongoing ischemic symptoms such as transient ischemic attacks, minor
             strokes, stroke-in-evolution, or clinical evidence of cerebral vasospasm within 2
             weeks prior to randomization. (If a CT scan, cerebral angiogram, or other imaging
             performed during the 2 weeks prior to randomization shows radiological vasospasm
             deemed by the treating physician to be potentially clinically significant, the subject
             is excluded.)

          -  Brain MRI imaging (DWI and FLAIR sequences) within 2 weeks prior to the endovascular
             aneurysm repair procedure as detailed in Section 8.2. Imaging must not demonstrate any
             focal ischemic stroke defined as a new region of restricted diffusion and/or a focal
             area of reduced perfusion on a relative mean transit time (rMTT) or relative time to
             peak (rTTP) map

          -  Male or female with a minimum age of 18 years on the day of enrolment.

          -  Female subjects of childbearing potential: Negative pregnancy test. After enrolment,
             blood will be drawn from women of childbearing potential for a confirmatory test of
             pregnancy as evaluated by a serum B-hCG test. The definition of non-childbearing
             potential includes the following:

               -  Surgically sterile (e.g., hysterectomy with or without oophorectomy; fallopian
                  tube ligation; endometrial ablation), at least 30 days prior to signature of the
                  Informed Consent form

               -  At least 5 years post-menopause (i.e., 6 years post last menstrual period), or
                  menopause confirmed by follicle-stimulating hormone (FSH) testing. Non-surgically
                  sterile females or females with undocumented post-menopausal status must be
                  willing to use a medically approved method of birth control for 3 months after
                  completion of dosing.

          -  Non-surgically sterile males or males with partners of childbearing potential must be
             willing to use condoms with spermicide for 3 months after completion of dosing.

          -  Body weight less than or equal to 180 kg.

          -  Normal or abnormal but not clinically significant findings in the

               -  non-neurological physical examination

               -  12-lead ECG

               -  PQ or PR interval less than or equal to 210 msec;

               -  In unruptured aneurysm cases, QTc interval less than 450 msec for males or 470
                  msec for females. For ruptured aneurysm cases, QTc interval is not restricted.

               -  vital signs

               -  blood pressure between 80-180/50-100 mm Hg,

               -  body temperature less than or equal to 38.5oC

          -  Informed consent and availability of the subject for the entire study period and
             willingness of the subject to adhere to protocol requirements, as evidenced by a
             signed Informed Consent Form.

        Exclusion Criteria

          -  Dissecting or mycotic brain aneurysm. Fusiform or atherosclerotic intracerebral
             aneurysms may be eligible for the trial if endovascular treatment is planned with a
             goal of exclusion of the aneurysm from the circulation.

          -  Planned endovascular vessel sacrifice as the primary modality for aneurysm treatment.

          -  Known history of life-threatening allergic reaction to any medication.

          -  Chronic renal disease defined as a baseline serum creatinine > 150 umol/L.

          -  Women who are pregnant, or have a positive urine or blood (β-hCG) pregnancy test.

          -  Women who are breastfeeding.

          -  Any clinically significant psychiatric or psychological disease, which would preclude
             the patient from completing the protocol.

          -  Pre-morbid (estimated) modified Rankin scale score of greater than 2.

          -  Previous serious traumatic brain injury that would preclude the patient from
             completing the protocol or preclude MRI analysis of small strokes.

          -  Patients with known HIV infection.

          -  Patients who are unable to have an MRI scan for any reason.

          -  Participation in a clinical trial with an investigational drug within 30 days
             preceding this study. Previous participation in the ENACT trial (e.g,, to treat a
             prior aneurysm), participation in another trial involving NA-1 or prior receipt of
             NA-1.

          -  Any other medical condition that the site investigator deems would put the patient at
             excessive risk of participation in the study or an expected life expectancy less than
             1 year or that would result in inability to collect clinical outcomes at 30 days.