Trial Outcomes & Findings for Trial of Oral Valproic Acid for Retinitis Pigmentosa (NCT NCT01233609)
NCT ID: NCT01233609
Last Updated: 2017-12-02
Results Overview
Mean change in visual field area from baseline to 52 weeks. Visual field area is measured with semi-automated kinetic perimetry (SKP) using the Octopus 900 (Haag-Streit) with the III4e target size for each eye and done at least twice to ensure reliable sessions; the visual field area measurements are averaged over the two sessions. Analysis performed with linear mixed model
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
90 participants
Primary outcome timeframe
baseline to week 52
Results posted on
2017-12-02
Participant Flow
Participant milestones
| Measure |
Valproic Acid
Subjects who receive valproic acid
Valproic Acid: One to four 250mg softgels by mouth daily (dose determined by body weight)
|
Placebo
Subjects who receive placebo
Placebo: Dosage per subject weight- same schedule as the active comparator
|
|---|---|---|
|
Overall Study
STARTED
|
46
|
44
|
|
Overall Study
COMPLETED
|
37
|
42
|
|
Overall Study
NOT COMPLETED
|
9
|
2
|
Reasons for withdrawal
| Measure |
Valproic Acid
Subjects who receive valproic acid
Valproic Acid: One to four 250mg softgels by mouth daily (dose determined by body weight)
|
Placebo
Subjects who receive placebo
Placebo: Dosage per subject weight- same schedule as the active comparator
|
|---|---|---|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
3
|
1
|
|
Overall Study
Adverse Event
|
2
|
1
|
|
Overall Study
Withdrawal by Subject
|
3
|
0
|
Baseline Characteristics
Trial of Oral Valproic Acid for Retinitis Pigmentosa
Baseline characteristics by cohort
| Measure |
Placebo
n=44 Participants
Subjects who receive placebo
Placebo: Dosage per subject weight- same schedule as the active comparator
|
Valproic Acid
n=46 Participants
Subjects who receive valproic acid
Valproic Acid: One to four 250mg softgels by mouth daily (dose determined by body weight)
|
Total
n=90 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
51.6 years
STANDARD_DEVIATION 10.9 • n=5 Participants
|
49.3 years
STANDARD_DEVIATION 12.3 • n=7 Participants
|
50.4 years
STANDARD_DEVIATION 11.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
38 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
79 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
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
43 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
87 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Genetic Mutations
RHO
|
22 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
|
Genetic Mutations
PRPF31
|
5 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Genetic Mutations
RP1
|
4 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Genetic Mutations
PRPF8
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Genetic Mutations
PRPH2
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Genetic Mutations
NR2E3
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Genetic Mutations
RHO and PRPH2
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Genetic Mutations
SNRNP200/ASCC3L1
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Genetic Mutations
TOPORS
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Genetic Mutations
IMPDH1
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Genetic Mutations
KLHL7
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Genetic Mutations
NR2E3 and TOPORS
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Genetic Mutations
RHO and ROM1
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: baseline to week 52Population: The analysis followed the intent-to-treat principle in that all randomized participants were included and analyzed according to their treatment assignment regardless of amount or type of treatment received. Only observed data were analyzed.
Mean change in visual field area from baseline to 52 weeks. Visual field area is measured with semi-automated kinetic perimetry (SKP) using the Octopus 900 (Haag-Streit) with the III4e target size for each eye and done at least twice to ensure reliable sessions; the visual field area measurements are averaged over the two sessions. Analysis performed with linear mixed model
Outcome measures
| Measure |
Placebo--Right Eye
n=42 eyes
Right eye of Placebo-treated patients
|
Placebo--Left Eye
n=42 eyes
Left eye of Placebo-treated patients
|
Valproic Acid--Right Eye
n=38 eyes
Right eye of Valproic acid-treated patients
|
Valproic Acid--Left Eye
n=38 eyes
Left eye of Valproic acid-treated patients
|
|---|---|---|---|---|
|
Mean Change in Visual Field Area From Baseline to 52 Weeks--III4e Isopter
|
-122.9 Visual field area (degrees squared)
Standard Deviation 543.60
|
-112.0 Visual field area (degrees squared)
Standard Deviation 584.63
|
-293.7 Visual field area (degrees squared)
Standard Deviation 736.56
|
-237.1 Visual field area (degrees squared)
Standard Deviation 691.76
|
SECONDARY outcome
Timeframe: baseline to week 52Population: The analysis followed the intent-to-treat principle in that all randomized participants were included and analyzed according to their treatment assignment regardless of amount or type of treatment received. Only observed data were analyzed.
Mean change in visual field area from baseline to 52 weeks. Visual field area is measured with semi-automated kinetic perimetry (SKP) using the Octopus 900 (Haag-Streit) with the I4e target size for each eye and done at least twice to ensure reliable sessions; the visual field area measurements are averaged over the two sessions. Analysis performed with linear mixed model
Outcome measures
| Measure |
Placebo--Right Eye
n=42 eyes
Right eye of Placebo-treated patients
|
Placebo--Left Eye
n=42 eyes
Left eye of Placebo-treated patients
|
Valproic Acid--Right Eye
n=38 eyes
Right eye of Valproic acid-treated patients
|
Valproic Acid--Left Eye
n=38 eyes
Left eye of Valproic acid-treated patients
|
|---|---|---|---|---|
|
Mean Change in Visual Field Area From Baseline to 52 Weeks--I4e Isopter
|
80.9 Visual field area (degrees squared)
Standard Deviation 406.2
|
115.7 Visual field area (degrees squared)
Standard Deviation 696.89
|
5.3 Visual field area (degrees squared)
Standard Deviation 759.46
|
19.5 Visual field area (degrees squared)
Standard Deviation 703.83
|
SECONDARY outcome
Timeframe: baseline to week 52Population: The analysis followed the intent-to-treat principle in that all randomized participants were included and analyzed according to their treatment assignment regardless of amount or type of treatment received. Only observed data were analyzed.
Mean change from baseline at week 52 for Full field Hill of Vision (Static perimetry)
Outcome measures
| Measure |
Placebo--Right Eye
n=41 eyes
Right eye of Placebo-treated patients
|
Placebo--Left Eye
n=41 eyes
Left eye of Placebo-treated patients
|
Valproic Acid--Right Eye
n=39 eyes
Right eye of Valproic acid-treated patients
|
Valproic Acid--Left Eye
n=39 eyes
Left eye of Valproic acid-treated patients
|
|---|---|---|---|---|
|
Static Perimetry by Treatment Arm--Full Field Hill of Vision
|
-0.3 db-steridians
Standard Deviation 2.55
|
-1.4 db-steridians
Standard Deviation 3.27
|
-0.2 db-steridians
Standard Deviation 5.11
|
-0.6 db-steridians
Standard Deviation 4.68
|
SECONDARY outcome
Timeframe: baseline to week 52Population: The analysis followed the intent-to-treat principle in that all randomized participants were included and analyzed according to their treatment assignment regardless of amount or type of treatment received. Only observed data were analyzed.
Mean Change from baseline to week 52 for Static Perimetry Volume --30 Degree Hill of Vision. Full field static perimetry protocol was followed using the Octopus 900 (Haag-Streit) for a single session for each eye.
Outcome measures
| Measure |
Placebo--Right Eye
n=41 eyes
Right eye of Placebo-treated patients
|
Placebo--Left Eye
n=41 eyes
Left eye of Placebo-treated patients
|
Valproic Acid--Right Eye
n=39 eyes
Right eye of Valproic acid-treated patients
|
Valproic Acid--Left Eye
n=39 eyes
Left eye of Valproic acid-treated patients
|
|---|---|---|---|---|
|
Static Perimetry Volume--30 Degree Hill of Vision
|
-0.3 db-steridans
Standard Deviation 0.61
|
-0.3 db-steridans
Standard Deviation 0.73
|
-0.2 db-steridans
Standard Deviation 1.07
|
-0.2 db-steridans
Standard Deviation 0.96
|
SECONDARY outcome
Timeframe: baseline to week 52Population: The analysis followed the intent-to-treat principle in that all randomized participants were included and analyzed according to their treatment assignment regardless of amount or type of treatment received. Only observed data were analyzed.
Mean change in best corrected visual acuity as assessed by ETDRS (Early Treatment Diabetic Retinopathy Study) method from baseline to week 52
Outcome measures
| Measure |
Placebo--Right Eye
n=40 Participants
Right eye of Placebo-treated patients
|
Placebo--Left Eye
n=40 Participants
Left eye of Placebo-treated patients
|
Valproic Acid--Right Eye
n=42 Participants
Right eye of Valproic acid-treated patients
|
Valproic Acid--Left Eye
n=42 Participants
Left eye of Valproic acid-treated patients
|
|---|---|---|---|---|
|
Mean Change From Baseline in Best Corrected Visual Acuity
|
-1.4 letters read correctly
Standard Deviation 5.21
|
0.0 letters read correctly
Standard Deviation 3.41
|
0.2 letters read correctly
Standard Deviation 4.41
|
1.3 letters read correctly
Standard Deviation 5.05
|
Adverse Events
Placebo
Serious events: 2 serious events
Other events: 41 other events
Deaths: 0 deaths
Valproic Acid
Serious events: 3 serious events
Other events: 45 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Placebo
n=44 participants at risk
Subjects who receive placebo
Placebo: Dosage per subject weight- same schedule as the active comparator
|
Valproic Acid
n=46 participants at risk
Subjects who receive valproic acid
Valproic Acid: One to four 250mg softgels by mouth daily (dose determined by body weight)
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
2.2%
1/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Injury, poisoning and procedural complications
Road Traffic Accidents
|
0.00%
0/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
2.2%
1/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Immune system disorders
Immunodeficiency common variable
|
0.00%
0/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
2.2%
1/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Eye disorders
Lens Dislocation
|
2.3%
1/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
0.00%
0/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Cardiac disorders
Atrial Fibrilation
|
2.3%
1/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
0.00%
0/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
Other adverse events
| Measure |
Placebo
n=44 participants at risk
Subjects who receive placebo
Placebo: Dosage per subject weight- same schedule as the active comparator
|
Valproic Acid
n=46 participants at risk
Subjects who receive valproic acid
Valproic Acid: One to four 250mg softgels by mouth daily (dose determined by body weight)
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
20.5%
9/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
6.5%
3/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Infections and infestations
Sinusitis
|
6.8%
3/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
15.2%
7/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Infections and infestations
Influenza
|
15.9%
7/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
2.2%
1/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Infections and infestations
Bronchitis
|
0.00%
0/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
6.5%
3/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Gastrointestinal disorders
Nausea
|
6.8%
3/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
17.4%
8/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
17.4%
8/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Gastrointestinal disorders
Diarrhea
|
2.3%
1/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
8.7%
4/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
4.5%
2/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
6.5%
3/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Gastrointestinal disorders
Gastroesophageal Reflux Disease
|
0.00%
0/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
6.5%
3/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Eye disorders
Vision Blurred
|
11.4%
5/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
6.5%
3/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Eye disorders
Cystoid Macular Oedema
|
2.3%
1/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
6.5%
3/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Investigations
Ammonia Increased
|
2.3%
1/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
15.2%
7/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Investigations
Alanine Aminotransferase Increased
|
4.5%
2/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
6.5%
3/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Investigations
Aspartate Aminotransferase Increased
|
2.3%
1/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
6.5%
3/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Investigations
Weight Increased
|
0.00%
0/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
8.7%
4/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Investigations
Hepatic Enzyme Increased
|
0.00%
0/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
6.5%
3/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Nervous system disorders
Headache
|
9.1%
4/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
17.4%
8/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Nervous system disorders
Dizziness
|
6.8%
3/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
4.3%
2/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
Nervous system disorders
Tremor
|
0.00%
0/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
6.5%
3/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
|
General disorders
Fatigue
|
6.8%
3/44 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
13.0%
6/46 • Treatment emergent adverse events are defined as those that occur between the first dose of study drug and the last dose of study drug plus 7 days.
|
Additional Information
Chief Drug Development Officer
Foundation Fighting Blindness Clinical Research Institute
Phone: 410 423 0581
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place