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

• Sponsor: University of Birmingham (Other)
• Overall Status: Completed
• CT.gov ID: NCT02017444
• Collaborator: (none)
• Enrollment: 31
• Location: 1
• Arms: 2
• Actual Duration (Months): 31.8
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

Assessing the safety and effectiveness of a 11-βhydroxysteroid dehydrogenase type 1 inhibitor (AZD4017), in a placebo controlled trial, in acute idiopathic intracranial hypertension (IIH) IIH is a condition of young, overweight women with characteristic raised intracranial pressure (pressure around the brain) leading to papilloedema (swelling of the nerve supplying the eye), visual loss and headaches. Medical literature (Cochrane review) demonstrates there is little evidence for the treatments used for IIH. Weight control appears the most effective method of improving symptoms but weight loss is difficult to maintain. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme which regulates local steroid levels and our previous research suggests it may influence the production of brain fluid(cerebrospinal fluid or CSF). 11β-HSD1 levels fall with weight loss and this is associated with with decreased intracranial pressure.

Our primary outcome is to determine whether AZD4017, an inhibitor of 11β-HSD1, will reduce the pressure in the brain and as a consequence improve IIH. Patients are eligible to enter the study if they are between 18-55 years old with acute (<6 months) IIH, signs of active disease (papilloedema and raised CSF pressure (>25 cmH20)), no other major illnesses and have no plans for pregnancy during the study period.

This is an MRC funded single centre, phase II, double-blinded, randomised control drug trial. It will be conducted at the University Hospital Birmingham and the University of Birmingham will act as Sponsor. Eligible participants will be randomly assigned to AZD4017 or a placebo ('dummy' with no active drug) for 3 months with a follow up a month later. Investigations during the study will include bloods, urine samples, pregnancy tests, lumbar punctures, DXA scans and small fat/skin biopsies. Participants will benefit from increased monitoring and a potential improvement in their condition.

We hypothesise that specific inhibition of 11β-HSD1 will decrease intracranial pressure and consequently treat patients with IIH, thus opening a new and entirely novel therapeutic avenue.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Intracranial Hypertension	Drug: AZD4017; Other: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Lowering Intracranial Pressure in Idiopathic Intracranial Hypertension: Assessing the Therapeutic Efficacy and Safety of an 11β-hydroxysteroid Dehydrogenase Type 1 Inhibitor (AZD4017). Phase II Study.
• Actual Study Start Date: Apr 25, 2014
• Actual Primary Completion Date: Dec 19, 2016
• Actual Study Completion Date: Dec 19, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Matched placebo tablet B.D for 12 weeks	Other: Placebo; Matched placebo (matched to AZD4017 arm)
Active Comparator: AZD4017 (11b-HSD1 inhibitor) AZD4017 400mg tablet B.D. for 12 weeks	Drug: AZD4017; Other Names: 11b-Hydroxysteroid dehydrogenase type 1 inhibitor

Outcome Measures

Primary Outcome Measures

1. Intracranial Pressure [12 weeks]

   ICP measured by lumbar puncture in cmCSF as the change from week 0 and week 12 of treatment, measured at baseline and week 12

Secondary Outcome Measures

1. Tinnitus [12 weeks]

   The temporal change in IIH symptoms (presence or absence of tinnitus), measured at baseline and week 12

2. Anthropometric Measurements (BMI) [12 weeks]

   The temporal change in Body Mass Index (in kg/m^2) over 12 weeks of treatment, measured at baseline and week 12

3. Visual Loss [12 weeks]

   The temporal change in IIH symptoms (presence or absence of visual loss, measured at baseline and week 12

4. Diplopia [12 weeks]

   The temporal change in IIH symptoms (presence or absence of diplopia, measured at baseline and week 12

5. Visual Obscuration [12 weeks]

   The temporal change in IIH symptoms (presence or absence of visual obscuration, measured at baseline and week 12

6. Headache [12 weeks]

   The temporal change in IIH symptoms (presence or absence of headache, measured at baseline and week 12

7. Visual Acuity [12 weeks]

   The temporal change in IIH visual function in both eyes (measured by LogMAR (log of the minimum angle of resolution) chart to assess visual acuity, between the baseline to week 12, measured at baseline and week 12

8. Papilloedema [12 weeks]

   The temporal change in papilloedema (evaluated at the end of trial follow up using stereoscopic fundus photographs by masked neuro-ophthalmologists to grade the images according to Frisen classification) measured at baseline and week 12. There are 6 grades, 0-5, 5 being the worst. The modified Frisén scale for grading papilledema using fundus photography is as follows: Grade 1 - C-Shaped halo with a temporal gap Grade 2 - The halo becomes circumferential Grade 3 - Loss of major vessels as they leave the disc Grade 4 - Loss of major vessels on the disc Grade 5 - Criteria of Grade IV + partial or total obscuration of all vessels on the disc For further details see e.g. Scott, C.J., et al., Diagnosis and grading of papilledema in patients with raised intracranial pressure using optical coherence tomography vs clinical expert assessment using a clinical staging scale. Arch. Ophthalmol, 2010. 128(6): p. 705-711.

9. Headache-associated Disability [12 weeks]

   The change in headache associated disability through the headache impact test-6 score (HIT 6), measured at baseline and week 12. This is scored 11-66 with higher scores indicating worse headache.

10. Adverse Events [16 weeks]

    The safety and tolerability profile of AZD4017 in female patients with IIH through adverse event reporting and safety bloods.

11. Serious Adverse Events [16 weeks]

    The safety and tolerability profile of AZD4017 in female patients with IIH through adverse event reporting and safety bloods.

12. OCT Total Average Retinal Nerve Fibre Layer Thickness (μm) [12 weeks]

    The temporal change in OCT Total average retinal nerve fibre layer thickness (μm), measured at baseline and week 12

13. Visual Field Mean Deviation [12 weeks]

    The temporal change in IIH visual function in both eyes using automated perimetry (Humphrey 24-2 central threshold) to measure the visual field mean deviation between the baseline to week 12

14. Log Contrast Sensitivity [12 weeks]

    The temporal change in IIH visual function in both eyes using a Pelli-Robson chart to evaluate log contrast sensitivity between the baseline to week 12

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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:

1. acute (<6 months),

2. active disease (papilloedema (Frisen grade greater than or equal to 1),

3. significantly raised ICP > 25cmH2O)

4. 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:

1. a vasectomised partner (sole partner) or tubal occlusion or

2. 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)

3. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Birmingham (Queen Elizabeth Hospital)	Birmingham	West Midlands	United Kingdom	B15 2TH

Sponsors and Collaborators

• University of Birmingham

Investigators

• Principal Investigator: Alexandra Sinclair, MbChb PhD, University of Birmingham

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dr Alexandra Sinclair, Chief Investigator, University of Birmingham
• ClinicalTrials.gov Identifier: NCT02017444
• Other Study ID Numbers: RG_13-022; 2013-003643-31; MR/K015184/1
• First Posted: Dec 20, 2013
• Last Update Posted: Oct 27, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Dr Alexandra Sinclair, Chief Investigator, University of Birmingham: Pseudotumor Cerebri; Benign Intracranial Hypertension; Headaches; Tinnitus; Papilledema; Blindness; Optic Disk; Intracranial Hypertension; Clinical Trial, Phase 2; 11beta-Hydroxysteroid Dehydrogenase Type 1; Obesity
• Additional relevant MeSH terms: Intracranial Hypertension; Pseudotumor Cerebri; Hypertension

Study Results

Participant Flow

Arm/Group Title	Placebo	AZD4017 (11b-HSD1 Inhibitor)
Arm/Group Description	Matched placebo tablet B.D for 12 weeks Placebo: Matched placebo (matched to AZD4017 arm)	AZD4017 400mg tablet B.D. for 12 weeks AZD4017
Period Title: Overall Study
STARTED	14	17
COMPLETED	12	17
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Placebo	AZD4017 (11b-HSD1 Inhibitor)	Total
Arm/Group Description	Matched placebo tablet B.D for 12 weeks Placebo: Matched placebo (matched to AZD4017 arm)	AZD4017 400mg tablet B.D. for 12 weeks AZD4017	Total of all reporting groups
Overall Participants	14	17	31
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.4 (8)	30.1 (5.9)	31.2 (6.9)
Sex: Female, Male (Count of Participants)
Female	14 100%	17 100%	31 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White British	13 92.9%	16 94.1%	29 93.5%
Asian/Asian British - Pakistani	0 0%	1 5.9%	1 3.2%
Asian/Asian British - Other Asian	1 7.1%	0 0%	1 3.2%
Region of Enrollment (participants) [Number]
United Kingdom	14 100%	17 100%	31 100%
Taking acetazolamide (yes/no) (Count of Participants)
Yes	4 28.6%	6 35.3%	10 32.3%
No	10 71.4%	11 64.7%	21 67.7%
Opening LP pressure (cmCSF) (cmCSF) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cmCSF]	32.7 (4.8)	33.7 (6.3)	33.3 (5.6)
Weight (kg) (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	108 (42.3)	97.9 (21.3)	102.6 (32.3)
BMI (kg/m^2) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	41.2 (16.6)	37.3 (7.2)	39.2 (12.6)
Headache Impact Test 6 (HIT-6) Score (HIT-6 score (higher is worse)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [HIT-6 score (higher is worse)]	63.4 (8.1)	63.8 (8.2)	63.6 (8)
Frisen grading (Worst eye) (Count of Participants)
1	2 14.3%	4 23.5%	6 19.4%
2	5 35.7%	9 52.9%	14 45.2%
3	3 21.4%	0 0%	3 9.7%
4	1 7.1%	2 11.8%	3 9.7%
5	0 0%	1 5.9%	1 3.2%
missing	1 7.1%	0 0%	1 3.2%
Presence of Pulsatile Tinnitus (Count of Participants)
Presence	13 92.9%	12 70.6%	25 80.6%
Absence	1 7.1%	5 29.4%	6 19.4%
Presence of visual loss (Count of Participants)
Presence	8 57.1%	4 23.5%	12 38.7%
Absence	6 42.9%	13 76.5%	19 61.3%
Presence of diplopia (Count of Participants)
Presence	5 35.7%	7 41.2%	12 38.7%
Absence	9 64.3%	10 58.8%	19 61.3%
Presence of Visual obscuration (Count of Participants)
Presence	6 42.9%	6 35.3%	12 38.7%
Absence	8 57.1%	11 64.7%	19 61.3%
Presence of headache (Count of Participants)
Presence	14 100%	16 94.1%	30 96.8%
Absence	0 0%	1 5.9%	1 3.2%

Outcome Measures

1. Primary Outcome

Title	Intracranial Pressure
Description	ICP measured by lumbar puncture in cmCSF as the change from week 0 and week 12 of treatment, measured at baseline and week 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	AZD4017 (11b-HSD1 Inhibitor)
Arm/Group Description	Matched placebo tablet B.D for 12 weeks Placebo: Matched placebo (matched to AZD4017 arm)	AZD4017 400mg tablet B.D. for 12 weeks AZD4017
Measure Participants	12	16
Mean (Standard Deviation) [cmCSF]	-0.3 (5.9)	-4.3 (5.7)

2. Secondary Outcome

Title	Tinnitus
Description	The temporal change in IIH symptoms (presence or absence of tinnitus), measured at baseline and week 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	AZD4017 (11b-HSD1 Inhibitor)
Arm/Group Description	Matched placebo tablet B.D for 12 weeks Placebo: Matched placebo (matched to AZD4017 arm)	AZD4017 400mg tablet B.D. for 12 weeks AZD4017
Measure Participants	12	17
Presence	7 50%	9 52.9%
Absence	5 35.7%	8 47.1%

3. Secondary Outcome

Title	Anthropometric Measurements (BMI)
Description	The temporal change in Body Mass Index (in kg/m^2) over 12 weeks of treatment, measured at baseline and week 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	AZD4017 (11b-HSD1 Inhibitor)
Arm/Group Description	Matched placebo tablet B.D for 12 weeks Placebo: Matched placebo (matched to AZD4017 arm)	AZD4017 400mg tablet B.D. for 12 weeks AZD4017
Measure Participants	11	17
Mean (Standard Deviation) [kg/m^2]	37.4 (8.4)	37.5 (6.9)

4. Secondary Outcome

Title	Visual Loss
Description	The temporal change in IIH symptoms (presence or absence of visual loss, measured at baseline and week 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	AZD4017 (11b-HSD1 Inhibitor)
Arm/Group Description	Matched placebo tablet B.D for 12 weeks Placebo: Matched placebo (matched to AZD4017 arm)	AZD4017 400mg tablet B.D. for 12 weeks AZD4017
Measure Participants	11	17
Presence	7 50%	6 35.3%
Absence	4 28.6%	11 64.7%

5. Secondary Outcome

Title	Diplopia
Description	The temporal change in IIH symptoms (presence or absence of diplopia, measured at baseline and week 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	AZD4017 (11b-HSD1 Inhibitor)
Arm/Group Description	Matched placebo tablet B.D for 12 weeks Placebo: Matched placebo (matched to AZD4017 arm)	AZD4017 400mg tablet B.D. for 12 weeks AZD4017
Measure Participants	12	17
Presence	1 7.1%	2 11.8%
Absence	11 78.6%	15 88.2%

6. Secondary Outcome

Title	Visual Obscuration
Description	The temporal change in IIH symptoms (presence or absence of visual obscuration, measured at baseline and week 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	AZD4017 (11b-HSD1 Inhibitor)
Arm/Group Description	Matched placebo tablet B.D for 12 weeks Placebo: Matched placebo (matched to AZD4017 arm)	AZD4017 400mg tablet B.D. for 12 weeks AZD4017
Measure Participants	11	17
Presence	2 14.3%	2 11.8%
Absence	9 64.3%	15 88.2%

7. Secondary Outcome

Title	Headache
Description	The temporal change in IIH symptoms (presence or absence of headache, measured at baseline and week 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	AZD4017 (11b-HSD1 Inhibitor)
Arm/Group Description	Matched placebo tablet B.D for 12 weeks Placebo: Matched placebo (matched to AZD4017 arm)	AZD4017 400mg tablet B.D. for 12 weeks AZD4017
Measure Participants	12	17
Presence	10 71.4%	13 76.5%
Absence	2 14.3%	4 23.5%

8. Secondary Outcome

Title	Visual Acuity
Description	The temporal change in IIH visual function in both eyes (measured by LogMAR (log of the minimum angle of resolution) chart to assess visual acuity, between the baseline to week 12, measured at baseline and week 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	AZD4017 (11b-HSD1 Inhibitor)
Arm/Group Description	Matched placebo tablet B.D for 12 weeks Placebo: Matched placebo (matched to AZD4017 arm)	AZD4017 400mg tablet B.D. for 12 weeks AZD4017
Measure Participants	14	17
Baseline LVA worst eye	0.13 (0.22)	0.08 (0.23)
Week 12 LVA worst eye	0.09 (0.18)	0.06 (0.15)

9. Secondary Outcome

Title	Papilloedema
Description	The temporal change in papilloedema (evaluated at the end of trial follow up using stereoscopic fundus photographs by masked neuro-ophthalmologists to grade the images according to Frisen classification) measured at baseline and week 12. There are 6 grades, 0-5, 5 being the worst. The modified Frisén scale for grading papilledema using fundus photography is as follows: Grade 1 - C-Shaped halo with a temporal gap Grade 2 - The halo becomes circumferential Grade 3 - Loss of major vessels as they leave the disc Grade 4 - Loss of major vessels on the disc Grade 5 - Criteria of Grade IV + partial or total obscuration of all vessels on the disc For further details see e.g. Scott, C.J., et al., Diagnosis and grading of papilledema in patients with raised intracranial pressure using optical coherence tomography vs clinical expert assessment using a clinical staging scale. Arch. Ophthalmol, 2010. 128(6): p. 705-711.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

NB: assessment missed for one participant at baseline

Arm/Group Title	Placebo	AZD4017 (11b-HSD1 Inhibitor)
Arm/Group Description	Matched placebo tablet B.D for 12 weeks Placebo: Matched placebo (matched to AZD4017 arm)	AZD4017 400mg tablet B.D. for 12 weeks AZD4017
Measure Participants	12	16
Frisen grade 0 baseline	0 0%	0 0%
Frisen grade 0 week 12	0 0%	2 11.8%
Frisen grade 1 baseline	2 14.3%	4 23.5%
Frisen grade 1 week 12	2 14.3%	5 29.4%
Frisen grade 2 baseline	5 35.7%	9 52.9%
Frisen grade 2 week 12	6 42.9%	8 47.1%
Frisen grade 3 baseline	3 21.4%	0 0%
Frisen grade 3 week 12	3 21.4%	0 0%
Frisen grade 4 baseline	1 7.1%	2 11.8%
Frisen grade 4 week 12	1 7.1%	1 5.9%
Frisen grade 5 baseline	0 0%	1 5.9%
Frisen grade 5 week 12	0 0%	0 0%

10. Secondary Outcome

Title	Headache-associated Disability
Description	The change in headache associated disability through the headache impact test-6 score (HIT 6), measured at baseline and week 12. This is scored 11-66 with higher scores indicating worse headache.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	AZD4017 (11b-HSD1 Inhibitor)
Arm/Group Description	Matched placebo tablet B.D for 12 weeks Placebo: Matched placebo (matched to AZD4017 arm)	AZD4017 400mg tablet B.D. for 12 weeks AZD4017
Measure Participants	11	15
Mean (Standard Error) [Score on HIT-6 scale]	59.8 (7.9)	60.1 (11.6)

11. Secondary Outcome

Title	Adverse Events
Description	The safety and tolerability profile of AZD4017 in female patients with IIH through adverse event reporting and safety bloods.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	AZD4017 (11b-HSD1 Inhibitor)
Arm/Group Description	Matched placebo tablet B.D for 12 weeks Placebo: Matched placebo (matched to AZD4017 arm)	AZD4017 400mg tablet B.D. for 12 weeks AZD4017
Measure Participants	14	17
Number [AEs related to intervention]	0	9

12. Secondary Outcome

Title	Serious Adverse Events
Description	The safety and tolerability profile of AZD4017 in female patients with IIH through adverse event reporting and safety bloods.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	AZD4017 (11b-HSD1 Inhibitor)
Arm/Group Description	Matched placebo tablet B.D for 12 weeks Placebo: Matched placebo (matched to AZD4017 arm)	AZD4017 400mg tablet B.D. for 12 weeks AZD4017
Measure Participants	14	17
Number [Serious adverse events]	1	0

13. Secondary Outcome

Title	OCT Total Average Retinal Nerve Fibre Layer Thickness (μm)
Description	The temporal change in OCT Total average retinal nerve fibre layer thickness (μm), measured at baseline and week 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

NB: assessment missed in participants of both arms due to centre capacity.

Arm/Group Title	Placebo	AZD4017 (11b-HSD1 Inhibitor)
Arm/Group Description	Matched placebo tablet B.D for 12 weeks Placebo: Matched placebo (matched to AZD4017 arm)	AZD4017 400mg tablet B.D. for 12 weeks AZD4017
Measure Participants	14	17
Total average retinal nerve fibre layer baseline worst ete	158.4 (83)	152 (68.7)
Total average retinal nerve fibre layer week 12 worst eye	143.2 (78.7)	139.7 (56.3)

14. Secondary Outcome

Title	Visual Field Mean Deviation
Description	The temporal change in IIH visual function in both eyes using automated perimetry (Humphrey 24-2 central threshold) to measure the visual field mean deviation between the baseline to week 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

NB: assessment at 12 weeks not completed for 2 participants.

Arm/Group Title	Placebo	AZD4017 (11b-HSD1 Inhibitor)
Arm/Group Description	Matched placebo tablet B.D for 12 weeks Placebo: Matched placebo (matched to AZD4017 arm)	AZD4017 400mg tablet B.D. for 12 weeks AZD4017
Measure Participants	14	17
Baseline MD worst eye	-3.4 (6.8)	-6.1 (5.4)
Week 12 MD worst eye	-2.2 (3.1)	-3.4 (3.2)

15. Secondary Outcome

Title	Log Contrast Sensitivity
Description	The temporal change in IIH visual function in both eyes using a Pelli-Robson chart to evaluate log contrast sensitivity between the baseline to week 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

NB: assessment at 12 weeks not completed for 2 participants (placebo).

Arm/Group Title	Placebo	AZD4017 (11b-HSD1 Inhibitor)
Arm/Group Description	Matched placebo tablet B.D for 12 weeks Placebo: Matched placebo (matched to AZD4017 arm)	AZD4017 400mg tablet B.D. for 12 weeks AZD4017
Measure Participants	12	13
Baseline LCS worst eye	1.63 (0.16)	1.63 (0.22)
Week 12 LCS worst eye	1.66 (0.12)	1.65 (0.15)

Adverse Events

Arm/Group Title	Placebo		AZD4017 (11b-HSD1 Inhibitor)
Arm/Group Description	Matched placebo tablet B.D for 12 weeks Placebo: Matched placebo (matched to AZD4017 arm)		AZD4017 400mg tablet B.D. for 12 weeks AZD4017
All Cause Mortality
	Placebo		AZD4017 (11b-HSD1 Inhibitor)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/17 (0%)
Serious Adverse Events
	Placebo		AZD4017 (11b-HSD1 Inhibitor)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/14 (7.1%)		0/17 (0%)
Eye disorders
IIH exacerbation	1/14 (7.1%)	1	0/17 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		AZD4017 (11b-HSD1 Inhibitor)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/14 (78.6%)		16/17 (94.1%)
Cardiac disorders
Cardiovascular	1/14 (7.1%)		1/17 (5.9%)
Ear and labyrinth disorders
Eyes, ear, nose, throat	6/14 (42.9%)		12/17 (70.6%)
Endocrine disorders
Endocrine	1/14 (7.1%)		1/17 (5.9%)
Gastrointestinal disorders
Gastro-intestinal	3/14 (21.4%)		8/17 (47.1%)
General disorders
Genito-urinary	0/14 (0%)		6/17 (35.3%)
Dermatological	5/14 (35.7%)		2/17 (11.8%)
Allergies	0/14 (0%)		1/17 (5.9%)
Other	5/14 (35.7%)		7/17 (41.2%)
Immune system disorders
Immunological	1/14 (7.1%)		0/17 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal	7/14 (50%)		6/17 (35.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasia	1/14 (7.1%)		0/17 (0%)
Nervous system disorders
Neurological	3/14 (21.4%)		7/17 (41.2%)
Psychiatric disorders
Psychological	4/14 (28.6%)		4/17 (23.5%)
Respiratory, thoracic and mediastinal disorders
Respiratory	3/14 (21.4%)		4/17 (23.5%)

Limitations/Caveats

A duration of 12 weeks was chosen for the evaluation of safety and tolerability, being the longest duration of dosing to date with AZD4017. This may not have been enough for meaningful evaluation of clinical outcomes. The sample size is small, which may have reduced power and limited meaningful evaluation of clinical measures: the trial was not designed to establish significant changes in the secondary clinical outcome measures.

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Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.