Trial Outcomes & Findings for Safety and Effectiveness of 11b-Hydroxysteroid Dehydrogenase Type 1 Inhibitor (AZD4017) to Treat Idiopathic Intracranial Hypertension. (NCT NCT02017444)
NCT ID: NCT02017444
Last Updated: 2021-10-27
Results Overview
ICP measured by lumbar puncture in cmCSF as the change from week 0 and week 12 of treatment, measured at baseline and week 12
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
31 participants
Primary outcome timeframe
12 weeks
Results posted on
2021-10-27
Participant Flow
Participant milestones
| Measure |
Placebo
Matched placebo tablet B.D for 12 weeks
Placebo: Matched placebo (matched to AZD4017 arm)
|
AZD4017 (11b-HSD1 Inhibitor)
AZD4017 400mg tablet B.D. for 12 weeks
AZD4017
|
|---|---|---|
|
Overall Study
STARTED
|
14
|
17
|
|
Overall Study
COMPLETED
|
12
|
17
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
Reasons for withdrawal
| Measure |
Placebo
Matched placebo tablet B.D for 12 weeks
Placebo: Matched placebo (matched to AZD4017 arm)
|
AZD4017 (11b-HSD1 Inhibitor)
AZD4017 400mg tablet B.D. for 12 weeks
AZD4017
|
|---|---|---|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Patient withdrawn day after randomisation as found to be ineligible. Did not return for follow up.
|
1
|
0
|
Baseline Characteristics
Safety and Effectiveness of 11b-Hydroxysteroid Dehydrogenase Type 1 Inhibitor (AZD4017) to Treat Idiopathic Intracranial Hypertension.
Baseline characteristics by cohort
| Measure |
Placebo
n=14 Participants
Matched placebo tablet B.D for 12 weeks
Placebo: Matched placebo (matched to AZD4017 arm)
|
AZD4017 (11b-HSD1 Inhibitor)
n=17 Participants
AZD4017 400mg tablet B.D. for 12 weeks
AZD4017
|
Total
n=31 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
32.4 years
STANDARD_DEVIATION 8 • n=93 Participants
|
30.1 years
STANDARD_DEVIATION 5.9 • n=4 Participants
|
31.2 years
STANDARD_DEVIATION 6.9 • n=27 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=93 Participants
|
17 Participants
n=4 Participants
|
31 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
White British
|
13 Participants
n=93 Participants
|
16 Participants
n=4 Participants
|
29 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Asian/Asian British - Pakistani
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Asian/Asian British - Other Asian
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Region of Enrollment
United Kingdom
|
14 participants
n=93 Participants
|
17 participants
n=4 Participants
|
31 participants
n=27 Participants
|
|
Taking acetazolamide (yes/no)
Yes
|
4 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
10 Participants
n=27 Participants
|
|
Taking acetazolamide (yes/no)
No
|
10 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
21 Participants
n=27 Participants
|
|
Opening LP pressure (cmCSF)
|
32.7 cmCSF
STANDARD_DEVIATION 4.8 • n=93 Participants
|
33.7 cmCSF
STANDARD_DEVIATION 6.3 • n=4 Participants
|
33.3 cmCSF
STANDARD_DEVIATION 5.6 • n=27 Participants
|
|
Weight (kg)
|
108 kg
STANDARD_DEVIATION 42.3 • n=93 Participants
|
97.9 kg
STANDARD_DEVIATION 21.3 • n=4 Participants
|
102.6 kg
STANDARD_DEVIATION 32.3 • n=27 Participants
|
|
BMI (kg/m^2)
|
41.2 kg/m^2
STANDARD_DEVIATION 16.6 • n=93 Participants
|
37.3 kg/m^2
STANDARD_DEVIATION 7.2 • n=4 Participants
|
39.2 kg/m^2
STANDARD_DEVIATION 12.6 • n=27 Participants
|
|
Headache Impact Test 6 (HIT-6) Score
|
63.4 HIT-6 score (higher is worse)
STANDARD_DEVIATION 8.1 • n=93 Participants
|
63.8 HIT-6 score (higher is worse)
STANDARD_DEVIATION 8.2 • n=4 Participants
|
63.6 HIT-6 score (higher is worse)
STANDARD_DEVIATION 8 • n=27 Participants
|
|
Frisen grading (Worst eye)
1
|
2 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
|
Frisen grading (Worst eye)
2
|
5 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
14 Participants
n=27 Participants
|
|
Frisen grading (Worst eye)
3
|
3 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Frisen grading (Worst eye)
4
|
1 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Frisen grading (Worst eye)
5
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Frisen grading (Worst eye)
missing
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Presence of Pulsatile Tinnitus
Presence
|
13 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
25 Participants
n=27 Participants
|
|
Presence of Pulsatile Tinnitus
Absence
|
1 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
|
Presence of visual loss
Presence
|
8 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
12 Participants
n=27 Participants
|
|
Presence of visual loss
Absence
|
6 Participants
n=93 Participants
|
13 Participants
n=4 Participants
|
19 Participants
n=27 Participants
|
|
Presence of diplopia
Presence
|
5 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
12 Participants
n=27 Participants
|
|
Presence of diplopia
Absence
|
9 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
19 Participants
n=27 Participants
|
|
Presence of Visual obscuration
Presence
|
6 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
12 Participants
n=27 Participants
|
|
Presence of Visual obscuration
Absence
|
8 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
19 Participants
n=27 Participants
|
|
Presence of headache
Presence
|
14 Participants
n=93 Participants
|
16 Participants
n=4 Participants
|
30 Participants
n=27 Participants
|
|
Presence of headache
Absence
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 12 weeksICP measured by lumbar puncture in cmCSF as the change from week 0 and week 12 of treatment, measured at baseline and week 12
Outcome measures
| Measure |
Placebo
n=12 Participants
Matched placebo tablet B.D for 12 weeks
Placebo: Matched placebo (matched to AZD4017 arm)
|
AZD4017 (11b-HSD1 Inhibitor)
n=16 Participants
AZD4017 400mg tablet B.D. for 12 weeks
AZD4017
|
|---|---|---|
|
Intracranial Pressure
|
-0.3 cmCSF
Standard Deviation 5.9
|
-4.3 cmCSF
Standard Deviation 5.7
|
SECONDARY outcome
Timeframe: 12 weeksThe temporal change in IIH symptoms (presence or absence of tinnitus), measured at baseline and week 12
Outcome measures
| Measure |
Placebo
n=12 Participants
Matched placebo tablet B.D for 12 weeks
Placebo: Matched placebo (matched to AZD4017 arm)
|
AZD4017 (11b-HSD1 Inhibitor)
n=17 Participants
AZD4017 400mg tablet B.D. for 12 weeks
AZD4017
|
|---|---|---|
|
Tinnitus
Presence
|
7 Participants
|
9 Participants
|
|
Tinnitus
Absence
|
5 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: 12 weeksThe temporal change in Body Mass Index (in kg/m\^2) over 12 weeks of treatment, measured at baseline and week 12
Outcome measures
| Measure |
Placebo
n=11 Participants
Matched placebo tablet B.D for 12 weeks
Placebo: Matched placebo (matched to AZD4017 arm)
|
AZD4017 (11b-HSD1 Inhibitor)
n=17 Participants
AZD4017 400mg tablet B.D. for 12 weeks
AZD4017
|
|---|---|---|
|
Anthropometric Measurements (BMI)
|
37.4 kg/m^2
Standard Deviation 8.4
|
37.5 kg/m^2
Standard Deviation 6.9
|
SECONDARY outcome
Timeframe: 12 weeksThe temporal change in IIH symptoms (presence or absence of visual loss, measured at baseline and week 12
Outcome measures
| Measure |
Placebo
n=11 Participants
Matched placebo tablet B.D for 12 weeks
Placebo: Matched placebo (matched to AZD4017 arm)
|
AZD4017 (11b-HSD1 Inhibitor)
n=17 Participants
AZD4017 400mg tablet B.D. for 12 weeks
AZD4017
|
|---|---|---|
|
Visual Loss
Presence
|
7 Participants
|
6 Participants
|
|
Visual Loss
Absence
|
4 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: 12 weeksThe temporal change in IIH symptoms (presence or absence of diplopia, measured at baseline and week 12
Outcome measures
| Measure |
Placebo
n=12 Participants
Matched placebo tablet B.D for 12 weeks
Placebo: Matched placebo (matched to AZD4017 arm)
|
AZD4017 (11b-HSD1 Inhibitor)
n=17 Participants
AZD4017 400mg tablet B.D. for 12 weeks
AZD4017
|
|---|---|---|
|
Diplopia
Presence
|
1 Participants
|
2 Participants
|
|
Diplopia
Absence
|
11 Participants
|
15 Participants
|
SECONDARY outcome
Timeframe: 12 weeksThe temporal change in IIH symptoms (presence or absence of visual obscuration, measured at baseline and week 12
Outcome measures
| Measure |
Placebo
n=11 Participants
Matched placebo tablet B.D for 12 weeks
Placebo: Matched placebo (matched to AZD4017 arm)
|
AZD4017 (11b-HSD1 Inhibitor)
n=17 Participants
AZD4017 400mg tablet B.D. for 12 weeks
AZD4017
|
|---|---|---|
|
Visual Obscuration
Presence
|
2 Participants
|
2 Participants
|
|
Visual Obscuration
Absence
|
9 Participants
|
15 Participants
|
SECONDARY outcome
Timeframe: 12 weeksThe temporal change in IIH symptoms (presence or absence of headache, measured at baseline and week 12
Outcome measures
| Measure |
Placebo
n=12 Participants
Matched placebo tablet B.D for 12 weeks
Placebo: Matched placebo (matched to AZD4017 arm)
|
AZD4017 (11b-HSD1 Inhibitor)
n=17 Participants
AZD4017 400mg tablet B.D. for 12 weeks
AZD4017
|
|---|---|---|
|
Headache
Presence
|
10 Participants
|
13 Participants
|
|
Headache
Absence
|
2 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: 12 weeksThe 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
Outcome measures
| Measure |
Placebo
n=14 Participants
Matched placebo tablet B.D for 12 weeks
Placebo: Matched placebo (matched to AZD4017 arm)
|
AZD4017 (11b-HSD1 Inhibitor)
n=17 Participants
AZD4017 400mg tablet B.D. for 12 weeks
AZD4017
|
|---|---|---|
|
Visual Acuity
Baseline LVA worst eye
|
0.13 LogMAR (log of the minimum angle of reso
Standard Deviation 0.22
|
0.08 LogMAR (log of the minimum angle of reso
Standard Deviation 0.23
|
|
Visual Acuity
Week 12 LVA worst eye
|
0.09 LogMAR (log of the minimum angle of reso
Standard Deviation 0.18
|
0.06 LogMAR (log of the minimum angle of reso
Standard Deviation 0.15
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: NB: assessment missed for one participant at baseline
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Matched placebo tablet B.D for 12 weeks
Placebo: Matched placebo (matched to AZD4017 arm)
|
AZD4017 (11b-HSD1 Inhibitor)
n=16 Participants
AZD4017 400mg tablet B.D. for 12 weeks
AZD4017
|
|---|---|---|
|
Papilloedema
Frisen grade 3 baseline
|
3 Participants
|
0 Participants
|
|
Papilloedema
Frisen grade 1 week 12
|
2 Participants
|
5 Participants
|
|
Papilloedema
Frisen grade 2 baseline
|
5 Participants
|
9 Participants
|
|
Papilloedema
Frisen grade 2 week 12
|
6 Participants
|
8 Participants
|
|
Papilloedema
Frisen grade 3 week 12
|
3 Participants
|
0 Participants
|
|
Papilloedema
Frisen grade 4 baseline
|
1 Participants
|
2 Participants
|
|
Papilloedema
Frisen grade 4 week 12
|
1 Participants
|
1 Participants
|
|
Papilloedema
Frisen grade 5 baseline
|
0 Participants
|
1 Participants
|
|
Papilloedema
Frisen grade 5 week 12
|
0 Participants
|
0 Participants
|
|
Papilloedema
Frisen grade 0 baseline
|
0 Participants
|
0 Participants
|
|
Papilloedema
Frisen grade 0 week 12
|
0 Participants
|
2 Participants
|
|
Papilloedema
Frisen grade 1 baseline
|
2 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: 12 weeksThe 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.
Outcome measures
| Measure |
Placebo
n=11 Participants
Matched placebo tablet B.D for 12 weeks
Placebo: Matched placebo (matched to AZD4017 arm)
|
AZD4017 (11b-HSD1 Inhibitor)
n=15 Participants
AZD4017 400mg tablet B.D. for 12 weeks
AZD4017
|
|---|---|---|
|
Headache-associated Disability
|
59.8 Score on HIT-6 scale
Standard Error 7.9
|
60.1 Score on HIT-6 scale
Standard Error 11.6
|
SECONDARY outcome
Timeframe: 16 weeksThe safety and tolerability profile of AZD4017 in female patients with IIH through adverse event reporting and safety bloods.
Outcome measures
| Measure |
Placebo
n=14 Participants
Matched placebo tablet B.D for 12 weeks
Placebo: Matched placebo (matched to AZD4017 arm)
|
AZD4017 (11b-HSD1 Inhibitor)
n=17 Participants
AZD4017 400mg tablet B.D. for 12 weeks
AZD4017
|
|---|---|---|
|
Adverse Events
|
0 AEs related to intervention
|
9 AEs related to intervention
|
SECONDARY outcome
Timeframe: 16 weeksThe safety and tolerability profile of AZD4017 in female patients with IIH through adverse event reporting and safety bloods.
Outcome measures
| Measure |
Placebo
n=14 Participants
Matched placebo tablet B.D for 12 weeks
Placebo: Matched placebo (matched to AZD4017 arm)
|
AZD4017 (11b-HSD1 Inhibitor)
n=17 Participants
AZD4017 400mg tablet B.D. for 12 weeks
AZD4017
|
|---|---|---|
|
Serious Adverse Events
|
1 Serious adverse events
|
0 Serious adverse events
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: NB: assessment missed in participants of both arms due to centre capacity.
The temporal change in OCT Total average retinal nerve fibre layer thickness (μm), measured at baseline and week 12
Outcome measures
| Measure |
Placebo
n=14 Participants
Matched placebo tablet B.D for 12 weeks
Placebo: Matched placebo (matched to AZD4017 arm)
|
AZD4017 (11b-HSD1 Inhibitor)
n=17 Participants
AZD4017 400mg tablet B.D. for 12 weeks
AZD4017
|
|---|---|---|
|
OCT Total Average Retinal Nerve Fibre Layer Thickness (μm)
Total average retinal nerve fibre layer baseline worst ete
|
158.4 μm
Standard Deviation 83
|
152 μm
Standard Deviation 68.7
|
|
OCT Total Average Retinal Nerve Fibre Layer Thickness (μm)
Total average retinal nerve fibre layer week 12 worst eye
|
143.2 μm
Standard Deviation 78.7
|
139.7 μm
Standard Deviation 56.3
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: NB: assessment at 12 weeks not completed for 2 participants.
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
Outcome measures
| Measure |
Placebo
n=14 Participants
Matched placebo tablet B.D for 12 weeks
Placebo: Matched placebo (matched to AZD4017 arm)
|
AZD4017 (11b-HSD1 Inhibitor)
n=17 Participants
AZD4017 400mg tablet B.D. for 12 weeks
AZD4017
|
|---|---|---|
|
Visual Field Mean Deviation
Baseline MD worst eye
|
-3.4 Visual field mean deviation
Standard Deviation 6.8
|
-6.1 Visual field mean deviation
Standard Deviation 5.4
|
|
Visual Field Mean Deviation
Week 12 MD worst eye
|
-2.2 Visual field mean deviation
Standard Deviation 3.1
|
-3.4 Visual field mean deviation
Standard Deviation 3.2
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: NB: assessment at 12 weeks not completed for 2 participants (placebo).
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
Outcome measures
| Measure |
Placebo
n=12 Participants
Matched placebo tablet B.D for 12 weeks
Placebo: Matched placebo (matched to AZD4017 arm)
|
AZD4017 (11b-HSD1 Inhibitor)
n=13 Participants
AZD4017 400mg tablet B.D. for 12 weeks
AZD4017
|
|---|---|---|
|
Log Contrast Sensitivity
Baseline LCS worst eye
|
1.63 Log contrast senstivity
Standard Deviation 0.16
|
1.63 Log contrast senstivity
Standard Deviation 0.22
|
|
Log Contrast Sensitivity
Week 12 LCS worst eye
|
1.66 Log contrast senstivity
Standard Deviation 0.12
|
1.65 Log contrast senstivity
Standard Deviation 0.15
|
Adverse Events
Placebo
Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths
AZD4017 (11b-HSD1 Inhibitor)
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=14 participants at risk
Matched placebo tablet B.D for 12 weeks
Placebo: Matched placebo (matched to AZD4017 arm)
|
AZD4017 (11b-HSD1 Inhibitor)
n=17 participants at risk
AZD4017 400mg tablet B.D. for 12 weeks
AZD4017
|
|---|---|---|
|
Eye disorders
IIH exacerbation
|
7.1%
1/14 • Number of events 1
|
0.00%
0/17
|
Other adverse events
| Measure |
Placebo
n=14 participants at risk
Matched placebo tablet B.D for 12 weeks
Placebo: Matched placebo (matched to AZD4017 arm)
|
AZD4017 (11b-HSD1 Inhibitor)
n=17 participants at risk
AZD4017 400mg tablet B.D. for 12 weeks
AZD4017
|
|---|---|---|
|
Cardiac disorders
Cardiovascular
|
7.1%
1/14
|
5.9%
1/17
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory
|
21.4%
3/14
|
23.5%
4/17
|
|
Gastrointestinal disorders
Gastro-intestinal
|
21.4%
3/14
|
47.1%
8/17
|
|
General disorders
Genito-urinary
|
0.00%
0/14
|
35.3%
6/17
|
|
Endocrine disorders
Endocrine
|
7.1%
1/14
|
5.9%
1/17
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal
|
50.0%
7/14
|
35.3%
6/17
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasia
|
7.1%
1/14
|
0.00%
0/17
|
|
Nervous system disorders
Neurological
|
21.4%
3/14
|
41.2%
7/17
|
|
Psychiatric disorders
Psychological
|
28.6%
4/14
|
23.5%
4/17
|
|
Immune system disorders
Immunological
|
7.1%
1/14
|
0.00%
0/17
|
|
General disorders
Dermatological
|
35.7%
5/14
|
11.8%
2/17
|
|
General disorders
Allergies
|
0.00%
0/14
|
5.9%
1/17
|
|
Ear and labyrinth disorders
Eyes, ear, nose, throat
|
42.9%
6/14
|
70.6%
12/17
|
|
General disorders
Other
|
35.7%
5/14
|
41.2%
7/17
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place