Trial Outcomes & Findings for A Study of the Structure and Function of the Retina in Adult Patients With Refractory Complex Partial Seizures Treated With Vigabatrin (Sabril®) (NCT NCT01278173)
NCT ID: NCT01278173
Last Updated: 2016-06-07
Results Overview
Mean change from the reference value in 30-2 SITA mean deviation, which was generated using the University of Iowa Visual Field Reading Center (VFRC) normative database and the Humphrey Field Analyzer (HFA) normative database. The reference value was defined as the average of the assessments performed at Visits 1 (baseline), 2 and 3 (first month of dosing). The mean change from the reference value are presented for Months 3, 6, 9 and 12. A negative change from the reference value indicates a decrease in the central visual field.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
65 participants
Primary outcome timeframe
Baseline (Month 0), Month 3, Month 6, Month 9, Month 12
Results posted on
2016-06-07
Participant Flow
Participant milestones
| Measure |
Sabril
Vigabatrin, 500 mg tablets, orally. Physicians will dose their patients according to guidance provided in the product label.
|
|---|---|
|
Overall Study
STARTED
|
65
|
|
Overall Study
COMPLETED
|
38
|
|
Overall Study
NOT COMPLETED
|
27
|
Reasons for withdrawal
| Measure |
Sabril
Vigabatrin, 500 mg tablets, orally. Physicians will dose their patients according to guidance provided in the product label.
|
|---|---|
|
Overall Study
Lack of Efficacy
|
13
|
|
Overall Study
Adverse Event
|
8
|
|
Overall Study
Administrative or other reason
|
4
|
|
Overall Study
Protocol Violation
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
A Study of the Structure and Function of the Retina in Adult Patients With Refractory Complex Partial Seizures Treated With Vigabatrin (Sabril®)
Baseline characteristics by cohort
| Measure |
Sabril
n=65 Participants
Vigabatrin, 500 mg tablets, orally. Physicians will dose their patients according to guidance provided in the product label.
|
|---|---|
|
Age, Continuous
|
39.8 years
STANDARD_DEVIATION 12.3 • n=99 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
37 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
58 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
65 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Baseline (Month 0), Month 3, Month 6, Month 9, Month 12Population: All patients who had received at least one dose of investigational medicinal product and who had a valid reference value assessment and at least one valid post-reference value assessment. The total number of patients included in the analysis set was 55. The actual number of patients analysed for each time point and eye is presented below (N = x).
Mean change from the reference value in 30-2 SITA mean deviation, which was generated using the University of Iowa Visual Field Reading Center (VFRC) normative database and the Humphrey Field Analyzer (HFA) normative database. The reference value was defined as the average of the assessments performed at Visits 1 (baseline), 2 and 3 (first month of dosing). The mean change from the reference value are presented for Months 3, 6, 9 and 12. A negative change from the reference value indicates a decrease in the central visual field.
Outcome measures
| Measure |
Sabril
n=55 Participants
Vigabatrin, 500 mg tablets, orally. Physicians will dose their patients according to guidance provided in the product label.
|
|---|---|
|
Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB)
HFA database: Left eye, 6 months (N=45)
|
-0.37 dB
Standard Deviation 1.15
|
|
Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB)
HFA database: Left eye, 9 months (N=40)
|
-0.33 dB
Standard Deviation 1.61
|
|
Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB)
VFRC database: Left eye, 3 months (N=50)
|
-0.28 dB
Standard Deviation 1.06
|
|
Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB)
VFRC database: Left eye, 6 months (N=45)
|
-0.24 dB
Standard Deviation 1.13
|
|
Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB)
VFRC database: Left eye, 9 months (N=39)
|
-0.14 dB
Standard Deviation 1.72
|
|
Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB)
VFRC database: Left eye, 12 months (N=36)
|
-0.13 dB
Standard Deviation 1.58
|
|
Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB)
VFRC database: Right eye, 3 months (N=50)
|
0.08 dB
Standard Deviation 1.20
|
|
Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB)
VFRC database: Right eye, 6 months (N=45)
|
-0.11 dB
Standard Deviation 1.40
|
|
Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB)
VFRC database: Right eye, 9 months (N=39)
|
0.02 dB
Standard Deviation 1.36
|
|
Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB)
VFRC database: Right eye, 12 months (N=36)
|
-0.27 dB
Standard Deviation 1.61
|
|
Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB)
HFA database: Left eye, 3 months (N=51)
|
-0.32 dB
Standard Deviation 1.13
|
|
Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB)
HFA database: Left eye, 12 months (N=37)
|
-0.15 dB
Standard Deviation 1.68
|
|
Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB)
HFA database: Right eye, 3 months (N=51)
|
0.00 dB
Standard Deviation 1.18
|
|
Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB)
HFA database: Right eye, 6 months (N=45)
|
-0.23 dB
Standard Deviation 1.40
|
|
Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB)
HFA database: Right eye, 9 months (N=40)
|
-0.07 dB
Standard Deviation 1.33
|
|
Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB)
HFA database: Right eye, 12 months (N=37)
|
-0.47 dB
Standard Deviation 1.60
|
PRIMARY outcome
Timeframe: Baseline (Month 0), Month 3, Month 6, Month 9, Month 12Population: All patients who had received at least one dose of IMP and who had a valid reference value assessment and at least one valid post-reference value assessment. The total number of patients included in the analysis set was 55. The actual number of patients analysed for each time point and eye is presented below (N = x).
Mean change from the reference value in average RNFL thickness (µm) as measured by SD-OCT. The reference value was defined as the average of the assessments performed at Visits 1 (baseline), 2 and 3 (first month of dosing). Thinning of the RNFL, that is, a negative change from the reference value, has been associated with ophthalmological disease.
Outcome measures
| Measure |
Sabril
n=55 Participants
Vigabatrin, 500 mg tablets, orally. Physicians will dose their patients according to guidance provided in the product label.
|
|---|---|
|
Change From Reference Value in Average RNFL (Retinal Nerve Fiber Layer) Thickness (µm) as Measured by SD-OCT (Spectral Domain-Optical Coherence Tomography)
Left eye, 3 months (N=54)
|
0.70 µm
Standard Deviation 2.56
|
|
Change From Reference Value in Average RNFL (Retinal Nerve Fiber Layer) Thickness (µm) as Measured by SD-OCT (Spectral Domain-Optical Coherence Tomography)
Left eye, 6 months (N=48)
|
4.15 µm
Standard Deviation 4.72
|
|
Change From Reference Value in Average RNFL (Retinal Nerve Fiber Layer) Thickness (µm) as Measured by SD-OCT (Spectral Domain-Optical Coherence Tomography)
Left eye, 9 months (N=44)
|
5.63 µm
Standard Deviation 4.30
|
|
Change From Reference Value in Average RNFL (Retinal Nerve Fiber Layer) Thickness (µm) as Measured by SD-OCT (Spectral Domain-Optical Coherence Tomography)
Left eye, 12 months (N=39)
|
6.45 µm
Standard Deviation 4.81
|
|
Change From Reference Value in Average RNFL (Retinal Nerve Fiber Layer) Thickness (µm) as Measured by SD-OCT (Spectral Domain-Optical Coherence Tomography)
Right eye, 3 months (N=52)
|
0.73 µm
Standard Deviation 2.20
|
|
Change From Reference Value in Average RNFL (Retinal Nerve Fiber Layer) Thickness (µm) as Measured by SD-OCT (Spectral Domain-Optical Coherence Tomography)
Right eye, 6 months (N=47)
|
4.21 µm
Standard Deviation 3.75
|
|
Change From Reference Value in Average RNFL (Retinal Nerve Fiber Layer) Thickness (µm) as Measured by SD-OCT (Spectral Domain-Optical Coherence Tomography)
Right eye, 9 months (N=43)
|
6.50 µm
Standard Deviation 4.67
|
|
Change From Reference Value in Average RNFL (Retinal Nerve Fiber Layer) Thickness (µm) as Measured by SD-OCT (Spectral Domain-Optical Coherence Tomography)
Right eye, 12 months (N=39)
|
7.19 µm
Standard Deviation 4.88
|
Adverse Events
Vigabatrin
Serious events: 9 serious events
Other events: 41 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Vigabatrin
n=65 participants at risk
|
|---|---|
|
Cardiac disorders
Atrial flutter
|
1.5%
1/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
Gastrointestinal disorders
Abdominal pain
|
1.5%
1/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
Infections and infestations
Pneumonia
|
1.5%
1/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
Infections and infestations
Septic shock
|
1.5%
1/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
Nervous system disorders
Convulsion
|
9.2%
6/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
Nervous system disorders
Partial seizures with secondary generalisation
|
1.5%
1/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
Nervous system disorders
Postictal paralysis
|
1.5%
1/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
Nervous system disorders
Postictal state
|
1.5%
1/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
Nervous system disorders
Somnolence
|
1.5%
1/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
Psychiatric disorders
Suicidal ideation
|
1.5%
1/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
Psychiatric disorders
Suicide attempt
|
1.5%
1/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
Surgical and medical procedures
Mitral valve repair
|
1.5%
1/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
Other adverse events
| Measure |
Vigabatrin
n=65 participants at risk
|
|---|---|
|
Eye disorders
Vision blurred
|
9.2%
6/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
Gastrointestinal disorders
Diarrhoea
|
6.2%
4/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
General disorders
Fatigue
|
6.2%
4/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
Injury, poisoning and procedural complications
Fall
|
12.3%
8/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
Investigations
Weight increased
|
7.7%
5/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
Nervous system disorders
Convulsion
|
20.0%
13/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
Nervous system disorders
Dizziness
|
10.8%
7/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
Nervous system disorders
Somnolence
|
6.2%
4/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
Psychiatric disorders
Depression
|
6.2%
4/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
Psychiatric disorders
Suicidal ideation
|
6.2%
4/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
|
Surgical and medical procedures
Vagal nerve stimulator implantation
|
6.2%
4/65 • Baseline to end of study
Treatment-Emergent Adverse Events are reported in this section
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place