Safety and Effectiveness of 11b-Hydroxysteroid Dehydrogenase Type 1 Inhibitor (AZD4017) to Treat Idiopathic Intracranial Hypertension.

Inclusion criteria

• Provision of informed consent prior to any study specific procedures.
• Female patients between 18 and 55 years
• Diagnosis of IIH by the Modified Dandy criteria1 with:

• acute (<6 months),
• active disease (papilloedema (Frisen grade greater than or equal to 1),
• significantly raised ICP > 25cmH2O)
• normal brain imaging during previous routine diagnostic work up (evaluated by either magnetic resonance venography or computerised tomography with venography).
• Patients must be willing to use one form of highly effective non-hormonal contraception. This would include:

• a vasectomised partner (sole partner) or tubal occlusion or
• copper containing IUD - all of which should be used in addition to a diaphragm or cervical/vault caps with barrier contraceptive (condom or spermicidal foam/gel/film/suppository)
• true abstinence (when this is in line with the preferred and usual lifestyle of the subject. Women should have been stable on their chosen method of birth control for a minimum of 2 months before entering the trial. Patients must agree to undergo a β-hCG pregnancy test and urine dipstick test at screening and urine dipstick testing at all trial visits (including the final follow up visit 4 weeks after discontinuation of study treatment). Note: the use of contraception and pregnancy testing would not be required if the screening LH/FSH levels demonstrate the patient is post-menopausal.
• Participants are able to continue other medications to treat their IIH e.g. acetazolamide, diuretics but this dose must remain fixed throughout the study.
• Patients who take aspirin therapy will be asked to discontinue aspirin 3 days prior to fat and skin biopsy if clinically safe to do so.
• Placebo treatment for the duration of the study must not be considered detrimental to the patient.
• Must be able to understand the consent form and comply with study requirements.

Exclusion criteria

• Optic nerve sheath fenestration.
• Patients who undergo CSF shunt insertion (which is not elective or pre- planned) during the study, as a result of deterioration will be withdrawn from the study.
• Abnormal neurological examination (aside from papilloedema and consequent visual loss or VI nerve palsy).
• Subjects with a secondary cause of raised intracranial pressure will be excluded (venous thrombosis, anaemia, drug causes (lithium, vitamin A, tetracycline or others deems responsible for the condition).
• Abnormal CSF contents (except for that compatible with a traumatic LP).
• Unable to perform a visual field reliably.

General Exclusion Criteria:

• Positive hCG or urine dipstick pregnancy test or planning to conceive in the 4 study months.
• Have eGFR calculated by MDRD equation of <60ml/min/1.73m2.
• Have any endocrine disorder, e.g. thyroid dysfunction. This excludes PCOS where there is a known association to IIH.
• Suspicion of or known Gilbert's disease.
• CK >2 x ULN on 2 consecutive measurements.
• ALT and/or AST >2 x ULN.
• ALP > ULN.
• Bilirubin (total) > 2 x ULN.
• Must not have donated blood within 2 months of screening and avoid further donations for 4 months following the study.
• Patient is, at the time of signing the informed consent, a user of recreational or illicit drugs (including marijuana) or has had a recent history (within the last year) of drug or alcohol abuse or dependence.
• Pregnant or breastfeeding mothers, unless willing to discontinue breastfeeding by the baseline visit.
• Have uncontrolled systemic hypertension (BP >160/90), on 3 successive measurements on the morning of the screening visit.
• Are receiving systemic (including vaginal/rectal) glucocorticoid treatment at the time of the screening visit. Note: Topical and inhaled are acceptable
• Are taking any hormone-based medication, including hormone contraceptives, at the time of screening.
• Are taking probenecid at the time of the screening visit.
• Have any screening laboratory abnormality that, in the investigator's judgement, is considered to be clinically significant or any screening laboratory value which is outside the Sponsor specified ranges at screening; testing may be repeated but must be resolved prior to the baseline visit.
• History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation or will influence the results .
• History or presence of significant gastrointestinal, hepatic , or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IP as judged by the investigator.
• Have been involved in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• Have participated in any other interventional study within 1 month prior to the screening visit. Participation in the IIH National database or other observational studies will not prevent enrolment to this study.
• Previous randomisation for treatment in the present study