Trial Outcomes & Findings for Study to Evaluate Effects of Emixustat Hydrochloride in Subjects With Proliferative Diabetic Retinopathy (NCT NCT02753400)
NCT ID: NCT02753400
Last Updated: 2021-05-19
Results Overview
All values for IL-1β were below the lower limit of detection and were recorded as zero. Tests for IP-10 and MCP-1 failed accuracy and stability testing during assay development and were dropped from the study. The assay for PDGF-AA could not be developed.and results were not reported.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
24 participants
Primary outcome timeframe
Baseline and 12 weeks
Results posted on
2021-05-19
Participant Flow
Subjects were enrolled from May 2016 through July 2017 at 8 sites in the United States
Participant milestones
| Measure |
Emixustat Hydrochloride
Week 1- Four tablets (2 placebo, 2 emixustat HCl Strength A)
Week 2- Four tablets (2 placebo, 2 emixustat HCl Strength B)
Week 3- Four tablets (2 placebo, 2 emixustat HCl Strength C)
Week 4- Four emixustat HCl tablets (Strength C)
All tablets are administered orally once daily. After week 4, all subjects will be held at a stable dose for the remainder of the 12-week dosing regimen.
emixustat hydrochloride: Tablet for oral administration
Placebo: Placebo tablets for oral administration contain only inactive ingredients
|
Placebo
Four placebo tablets are administered orally once daily for 12 weeks; Subjects in the placebo group will be mock-titrated on the same schedule as those in the active arm.
Placebo: Placebo tablets for oral administration contain only inactive ingredients
|
|---|---|---|
|
Overall Study
STARTED
|
12
|
12
|
|
Overall Study
COMPLETED
|
7
|
11
|
|
Overall Study
NOT COMPLETED
|
5
|
1
|
Reasons for withdrawal
| Measure |
Emixustat Hydrochloride
Week 1- Four tablets (2 placebo, 2 emixustat HCl Strength A)
Week 2- Four tablets (2 placebo, 2 emixustat HCl Strength B)
Week 3- Four tablets (2 placebo, 2 emixustat HCl Strength C)
Week 4- Four emixustat HCl tablets (Strength C)
All tablets are administered orally once daily. After week 4, all subjects will be held at a stable dose for the remainder of the 12-week dosing regimen.
emixustat hydrochloride: Tablet for oral administration
Placebo: Placebo tablets for oral administration contain only inactive ingredients
|
Placebo
Four placebo tablets are administered orally once daily for 12 weeks; Subjects in the placebo group will be mock-titrated on the same schedule as those in the active arm.
Placebo: Placebo tablets for oral administration contain only inactive ingredients
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
0
|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
Baseline Characteristics
Study to Evaluate Effects of Emixustat Hydrochloride in Subjects With Proliferative Diabetic Retinopathy
Baseline characteristics by cohort
| Measure |
Emixustat Hydrochloride
n=12 Participants
Week 1- Four tablets (2 placebo, 2 emixustat HCl Strength A)
Week 2- Four tablets (2 placebo, 2 emixustat HCl Strength B)
Week 3- Four tablets (2 placebo, 2 emixustat HCl Strength C)
Week 4- Four emixustat HCl tablets (Strength C)
All tablets are administered orally once daily. After week 4, all subjects will be held at a stable dose for the remainder of the 12-week dosing regimen.
emixustat hydrochloride: Tablet for oral administration
Placebo: Placebo tablets for oral administration contain only inactive ingredients
|
Placebo
n=12 Participants
Four placebo tablets are administered orally once daily for 12 weeks; Subjects in the placebo group will be mock-titrated on the same schedule as those in the active arm.
Placebo: Placebo tablets for oral administration contain only inactive ingredients
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
52.1 years
STANDARD_DEVIATION 7.06 • n=5 Participants
|
47.4 years
STANDARD_DEVIATION 11.29 • n=7 Participants
|
49.8 years
STANDARD_DEVIATION 9.52 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
10 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=5 Participants
|
12 participants
n=7 Participants
|
24 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and 12 weeksPopulation: Not all subjects had primary endpoint end-of-treatment data.
All values for IL-1β were below the lower limit of detection and were recorded as zero. Tests for IP-10 and MCP-1 failed accuracy and stability testing during assay development and were dropped from the study. The assay for PDGF-AA could not be developed.and results were not reported.
Outcome measures
| Measure |
Emixustat Hydrochloride
n=12 Participants
Week 1- Four tablets (2 placebo, 2 emixustat HCl Strength A)
Week 2- Four tablets (2 placebo, 2 emixustat HCl Strength B)
Week 3- Four tablets (2 placebo, 2 emixustat HCl Strength C)
Week 4- Four emixustat HCl tablets (Strength C)
All tablets are administered orally once daily. After week 4, all subjects will be held at a stable dose for the remainder of the 12-week dosing regimen.
emixustat hydrochloride: Tablet for oral administration
Placebo: Placebo tablets for oral administration contain only inactive ingredients
|
Placebo
n=11 Participants
Four placebo tablets are administered orally once daily for 12 weeks; Subjects in the placebo group will be mock-titrated on the same schedule as those in the active arm.
Placebo: Placebo tablets for oral administration contain only inactive ingredients
|
|---|---|---|
|
Change in Aqueous Humor Concentration of the Following Biomarkers:IL-6, IL-8, IP-10, PDGF-AA, TGFβ-1, MCP-1, IL-1β, and VEGF, to be Reported in pg/mL Values
IL-6, change from baseline
|
45.6 pg/ml
Standard Deviation 137.1
|
4.9 pg/ml
Standard Deviation 12.6
|
|
Change in Aqueous Humor Concentration of the Following Biomarkers:IL-6, IL-8, IP-10, PDGF-AA, TGFβ-1, MCP-1, IL-1β, and VEGF, to be Reported in pg/mL Values
IL-8, change from baseline
|
4.2 pg/ml
Standard Deviation 5.1
|
2.6 pg/ml
Standard Deviation 4.6
|
|
Change in Aqueous Humor Concentration of the Following Biomarkers:IL-6, IL-8, IP-10, PDGF-AA, TGFβ-1, MCP-1, IL-1β, and VEGF, to be Reported in pg/mL Values
TGFβ-1, change from baseline
|
-19.9 pg/ml
Standard Deviation 32.4
|
-17.5 pg/ml
Standard Deviation 43.7
|
|
Change in Aqueous Humor Concentration of the Following Biomarkers:IL-6, IL-8, IP-10, PDGF-AA, TGFβ-1, MCP-1, IL-1β, and VEGF, to be Reported in pg/mL Values
VEGF, change from baseline
|
-38.0 pg/ml
Standard Deviation 115.1
|
-24.8 pg/ml
Standard Deviation 277.2
|
Adverse Events
Emixustat Hydrochloride
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Placebo
Serious events: 2 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Emixustat Hydrochloride
n=12 participants at risk
Week 1- Four tablets (2 placebo, 2 emixustat HCl Strength A)
Week 2- Four tablets (2 placebo, 2 emixustat HCl Strength B)
Week 3- Four tablets (2 placebo, 2 emixustat HCl Strength C)
Week 4- Four emixustat HCl tablets (Strength C)
All tablets are administered orally once daily. After week 4, all subjects will be held at a stable dose for the remainder of the 12-week dosing regimen.
emixustat hydrochloride: Tablet for oral administration
Placebo: Placebo tablets for oral administration contain only inactive ingredients
|
Placebo
n=11 participants at risk
Four placebo tablets are administered orally once daily for 12 weeks; Subjects in the placebo group will be mock-titrated on the same schedule as those in the active arm.
Placebo: Placebo tablets for oral administration contain only inactive ingredients
|
|---|---|---|
|
Infections and infestations
Cellulitis
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Number of events 1 • Day 115
|
|
Investigations
Blood potassium increased
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Number of events 1 • Day 115
|
Other adverse events
| Measure |
Emixustat Hydrochloride
n=12 participants at risk
Week 1- Four tablets (2 placebo, 2 emixustat HCl Strength A)
Week 2- Four tablets (2 placebo, 2 emixustat HCl Strength B)
Week 3- Four tablets (2 placebo, 2 emixustat HCl Strength C)
Week 4- Four emixustat HCl tablets (Strength C)
All tablets are administered orally once daily. After week 4, all subjects will be held at a stable dose for the remainder of the 12-week dosing regimen.
emixustat hydrochloride: Tablet for oral administration
Placebo: Placebo tablets for oral administration contain only inactive ingredients
|
Placebo
n=11 participants at risk
Four placebo tablets are administered orally once daily for 12 weeks; Subjects in the placebo group will be mock-titrated on the same schedule as those in the active arm.
Placebo: Placebo tablets for oral administration contain only inactive ingredients
|
|---|---|---|
|
Eye disorders
DELAYED DARK ADAPTATION
|
75.0%
9/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Eye disorders
BLINDNESS DAY
|
33.3%
4/12 • Day 115
|
27.3%
3/11 • Day 115
|
|
Eye disorders
VISION BLURRED
|
8.3%
1/12 • Day 115
|
54.5%
6/11 • Day 115
|
|
Eye disorders
VISUAL IMPAIRMENT
|
50.0%
6/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Eye disorders
VITREOUS FLOATERS
|
33.3%
4/12 • Day 115
|
18.2%
2/11 • Day 115
|
|
Eye disorders
VISUAL ACUITY REDUCED
|
33.3%
4/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Eye disorders
CHROMATOPSIA
|
33.3%
4/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Investigations
VISUAL ACUITY TESTS ABNORMAL
|
16.7%
2/12 • Day 115
|
18.2%
2/11 • Day 115
|
|
Eye disorders
VITREOUS HAEMORRHAGE
|
25.0%
3/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Eye disorders
DIABETIC RETINAL OEDEMA
|
8.3%
1/12 • Day 115
|
18.2%
2/11 • Day 115
|
|
Eye disorders
ERYTHROPSIA
|
25.0%
3/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Nervous system disorders
HEADACHE
|
16.7%
2/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Eye disorders
PHOTOPHOBIA
|
8.3%
1/12 • Day 115
|
18.2%
2/11 • Day 115
|
|
Eye disorders
RETINAL NEOVASCULARISATION
|
8.3%
1/12 • Day 115
|
18.2%
2/11 • Day 115
|
|
Eye disorders
RETINAL ANEURYSM
|
16.7%
2/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Eye disorders
RETINAL DETACHMENT
|
16.7%
2/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Eye disorders
RETINAL EXUDATES
|
0.00%
0/12 • Day 115
|
18.2%
2/11 • Day 115
|
|
Eye disorders
RETINAL HAEMORRHAGE
|
8.3%
1/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Eye disorders
VITREOUS DETACHMENT
|
16.7%
2/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Investigations
BLOOD GLUCOSE INCREASED
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Investigations
BLOOD POTASSIUM INCREASED
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Respiratory, thoracic and mediastinal disorders
BRONCHITIS VIRAL
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Eye disorders
CATARACT
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Eye disorders
CATARACT CORTICAL
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Infections and infestations
CELLULITIS
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Musculoskeletal and connective tissue disorders
COSTOCHONDRITIS
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Metabolism and nutrition disorders
DIABETES MELLITUS
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Eye disorders
DIABETIC RETINOPATHY
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Nervous system disorders
DIZZINESS
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Eye disorders
EYE IRRITATION
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Eye disorders
EYE PAIN
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Eye disorders
EYE PRURITUS
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
General disorders
FATIGUE
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Metabolism and nutrition disorders
FLUID RETENTION
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Eye disorders
FOREIGN BODY SENSATION IN EYES
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Investigations
HAEMATOCRIT DECREASED
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Investigations
HAEMOGLOBIN DECREASED
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Vascular disorders
HOT FLUSH
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Metabolism and nutrition disorders
HYPERKALAEMIA
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Vascular disorders
HYPERTENSION
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Metabolism and nutrition disorders
HYPOTHYROIDISM
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Musculoskeletal and connective tissue disorders
LIGAMENT SPRAIN
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Infections and infestations
LOWER RESPIRATORY TRACT INFECTION
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Eye disorders
MACULAR FIBROSIS
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Infections and infestations
NASOPHARYNGITIS
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Gastrointestinal disorders
NAUSEA
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Musculoskeletal and connective tissue disorders
NECK PAIN
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Nervous system disorders
NEUROPATHY PERIPHERAL
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Eye disorders
NIGHT BLINDNESS
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
General disorders
OEDEMA PERIPHERAL
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Infections and infestations
PNEUMONIA
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Injury, poisoning and procedural complications
PROCEDURAL PAIN
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Eye disorders
PUNCTATE KERATITIS
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Eye disorders
RETINAL CYST
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Infections and infestations
SINUSITIS
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Injury, poisoning and procedural complications
SKIN ABRASION
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Infections and infestations
URINARY TRACT INFECTION
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Eye disorders
VISUAL BRIGHTNESS
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Eye disorders
VITREOUS ADHESIONS
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Gastrointestinal disorders
VOMITING
|
0.00%
0/12 • Day 115
|
9.1%
1/11 • Day 115
|
|
Investigations
WEIGHT INCREASED
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
|
Eye disorders
XANTHOPSIA
|
8.3%
1/12 • Day 115
|
0.00%
0/11 • Day 115
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place