A Study of the Structure and Function of the Retina in Adult Patients With Refractory Complex Partial Seizures Treated With Vigabatrin (Sabril®)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Lundbeck LLC
ClinicalTrials.gov Identifier:
NCT01278173
First received: January 14, 2011
Last updated: April 28, 2016
Last verified: April 2016
  Purpose
The purpose of the study is to evaluate the change in visual fields by means of automated static perimetry and to evaluate the change in retinal structure by means of spectral domain optical coherence tomography (SD-OCT) in adult patients with refractory complex partial seizures (CPS) being treated with vigabatrin (Sabril®)

Condition Intervention Phase
Adult Refractory Complex Partial Seizures
Drug: Sabril
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: A Prospective, Open-label Study of the Structure and Function of the Retina in Adult Patients With Refractory Complex Partial Seizures Treated With Vigabatrin (Sabril®)

Resource links provided by NLM:


Further study details as provided by Lundbeck LLC:

Primary Outcome Measures:
  • Mean Change From Reference Value in Field Width as Measured by 30-2 SITA Fast in Field Sensitivity (Mean Deviation - MD in dB) [ Time Frame: Baseline (Month 0), Month 3, Month 6, Month 9, Month 12 ] [ Designated as safety issue: Yes ]
    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.

  • Change From Reference Value in Average RNFL (Retinal Nerve Fiber Layer) Thickness (µm) as Measured by SD-OCT (Spectral Domain-Optical Coherence Tomography) [ Time Frame: Baseline (Month 0), Month 3, Month 6, Month 9, Month 12 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 65
Study Start Date: December 2010
Study Completion Date: May 2015
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Sabril Drug: Sabril
Sabril: 500 mg tablets, orally. Physicians will dose their patients according to guidance provided in the product label.
Other Name: Vigabatrin

Detailed Description:

Multicenter, prospective open-label study with approximately 25 sites in the US that specialize in caring for adult patients with refractory CPS

  • Sites must have access to Humphrey static perimetry and to Spectralis SD-OCT.
  • All vision test results will be sent to the central readers for evaluation.
  • Additional study tests:

    • The Columbia Suicide Severity Rating Scale (C-SSRS)
    • The National Eye Institute Visual Field Questionnaire-39 (NEI VFQ-39)
    • A whole blood sample for specific analysis of DNA characteristics
    • An optional whole blood sample for exploratory analysis of DNA characteristics
    • Plasma samples for bioanalytical analysis of vigabatrin and blood samples for taurine biomarker analysis
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Important Inclusion Criteria:

  1. The patient speaks English or Spanish.
  2. The patient has had no prior exposure to Sabril.
  3. To begin Sabril therapy for the treatment of CPS.
  4. Male or female ≥18 years of age.
  5. The patient has refractory CPS:

    1. The patient has complex partial epilepsy of more than 1 year duration and no other seizure type within the past year except for partial seizures secondarily generalized.
    2. The patient has failed because of lack of efficacy 3 or more prior or concurrent treatment trials including 3 or more anti-epileptic drugs (AEDs) of differing pharmacologic mechanisms administered as monotherapy or polytherapy.
    3. The patient is taking at least 1 AED. A vagal nerve stimulator is not counted as an AED.
    4. The patient reports an average of 2 or more seizures per month averaged over the prior 3 months.
  6. The patient is deemed by the treating neurologist and ophthalmologist to be able to reliably complete perimetry testing.
  7. The initial (Visit 1) SD-OCT and static perimetry readings tests must be performed and assessed for technical adequacy by the SD-OCT and perimetry central readers prior to the first dose of Sabril. The initial (Visit 1) tangent corner test must be performed prior to the first dose of Sabril.

Exclusion Criteria:

  1. Prior exposure to Sabril.
  2. Pre-existing ocular or neurological disease that might affect bilateral visual fields or interfere with perimetry (e.g., aphakia, visually significant cataract, glaucoma, diabetes mellitus, ischemic optic neuropathy, multiple sclerosis). Patients with stable visual field defects from CNS lesions (e.g., epilepsy surgery more than 6 months prior to receiving Sabril) may be enrolled.
  3. Concurrent exposure to medications with known or suspected retinal or optic nerve toxicity.
  4. Concurrent use of an investigational agent or device or such use within 30 days of entering the study.
  5. Concurrent use of the ketogenic or similar diet.
  6. For any reason, the patient is considered by the investigator to be an unsuitable candidate for the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01278173

  Show 22 Study Locations
Sponsors and Collaborators
Lundbeck LLC
Investigators
Study Director: Email contact via H. Lundbeck A/S LundbeckClinicalTrials@lundbeck.com
  More Information

Responsible Party: Lundbeck LLC
ClinicalTrials.gov Identifier: NCT01278173     History of Changes
Other Study ID Numbers: 13098A 
Study First Received: January 14, 2011
Results First Received: April 28, 2016
Last Updated: April 28, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Lundbeck LLC:
Vigabatrin-associated vision change
Adult refractory complex partial seizures
CPS
Epilepsy
Seizures
Brain diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Enzyme Inhibitors
GABA Agents

Additional relevant MeSH terms:
Vigabatrin
Seizures
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Anticonvulsants
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 29, 2016