This is a Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of SFX-01 in Subarachnoid Haemorrhage, with exploratory evaluations of efficacy.
The study is a randomised, double-blind, parallel-group design comparing SFX-01 (300 mg) taken orally as capsules or as a suspension via a nasogastric tube (NG) twice-daily for up to 28 days versus placebo in 90 patients who have had SAH and present within 48 hours of ictus. Subjects will receive SFX-01/Placebo in order to review potential outcomes investigating the long-term complications of SAH such as Delayed Cerebral Ischaemia, as reflected by Trans-Cranial Doppler (TCD) readings. The objective is to demonstrate safety and search for signals of efficacy in patients that have had SAH. A sub-study will be conducted in up to 12 patients where an External Ventricular Drain (EVD) fitted; serial CSF samples will be taken pre- \& post-dose on two occasions to determine pharmacokinetics of Sulforaphane in CSF in comparison with plasma pharmacokinetics. Sub-study patients will undergo all other procedures (with the exception of lumbar puncture). Treatment duration is up to 28 days; follow up duration is 28 days, three and six months. The planned trial period is 24 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
90
Southampton General Hospital
Southampton, Hampshire, United Kingdom
Western General Hospital
Edinburgh, United Kingdom
The Royal London Hospital
London, United Kingdom
Number of participants with treatment-related adverse events as assessed by Common Toxicity Criteria
To evaluate the safety of up to 28 days of SFX-01 dosed at up to 96 mg Sulforaphane (SFN) per day
Time frame: up to 28 days
Maximum CSF Concentration [Cmax],
To detect the presence of SFN in Cerebrospinal Fluid (CSF)
Time frame: up to 28 days
Number of participants with treatment related reduction in middle cerebral artery (MCA) peak flow velocity following Subarachnoid Haemorrhage (SAH) measured by trans cranial doppler ultrasound
To determine if a minimum of 7 days treatment with SFX-01 reduces Middle Cerebral Artery (MCA) peak flow velocity following Subarachnoid Haemorrhage (SAH).
Time frame: up to 28 days
modified Rankin Scale
To determine if a minimum of 7 days treatment with SFX-01 improves clinical outcome following SAH as measured using the modified Rankin Scale assessed at 7 , 28, 90 and 180 days post ictus.
Time frame: up to 180 days post ictus
Plasma PK
To determine plasma SFN levels (and its metabolites) with treatment with SFX-01 (300mg bid).
Time frame: up to 28 days
CSF drug levels
To determine CSF drug levels following treatment with SFX-01 (300mg bid).
Time frame: up to 14 days
Serum Haptoglobin levels
To determine if up to 28 days treatment with SFX-01 increases serum haptoglobin (HP) levels following SAH
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Time frame: Up to 28 days
Delayed Cerebral Ischaemia
To determine if up to 28 days treatment with SFX-01 can reduce the incidence of Delayed Cerebral Ischaemia (DCI) following SAH.
Time frame: Up to 28 days