Clinical trial NCT01501383: A Study to Evaluate the Efficacy and Safety of VX-765 in Subjects With Treatment-Resistant Partial Epilepsy
Official title: A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study to Evaluate the Efficacy and Safety of VX-765 in Subjects With Treatment-Resistant Partial Epilepsy With a 24-Week Open-Label Extension
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Epilepsy
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2011-12-29
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy, safety and tolerability of VX-765 in subjects with treatment-resistant partial epilepsy.


Eligibility criteria: Part A and Part B Inclusion Criteria:

* Males or females aged 18 to 64 years with a body mass index between 18 and 35 (kg/m2)
* Subjects who have completed the assigned study treatment in Part A may enter Part B if eligible per protocol
* Male or female subjects must agree to use acceptable contraceptive methods, as described in the protocol
* Must have a diagnosis and history of treatment-resistant partial-onset epilepsy for which they are taking 1 to 4 concomitant AEDs at the time of Screening Period
* Have had at least 1 electroencephalogram consistent with partial epilepsy
* Must have had at least 6 partial-onset seizures and a seizure-free period of no more than 3 weeks (21 days) during the Baseline Period.
* Subjects with stable medical conditions (e.g., cannot have a condition that will interfere with the conduct of the study or cause a known increase in risk of the intervention) as determined by the principal investigator
* Must be able and willing to provide written informed consent to participate
* Must be able to understand and comply with protocol requirements and instructions

Part A and Part B Exclusion Criteria:

* Subjects who are male and their female partner (if of childbearing potential) does not agree to use medically approved methods of contraception as described in the protocol for the duration od the study and for 90 days after last dose of study drug
* Subjects who are male and have a female partner who is pregnant, nursing, or is planning to become pregnant during the study period, or within 90 days of the last dose of study drug.
* Subjects who are pregnant or lactating, or who are of reproductive potential who do not agree to use medically approved birth control methods
* History of nonepileptic, transient alterations in consciousness
* History of status epilepticus in the past 12 months before the screening visit
* Subjects whose seizure frequency cannot be quantified (i.e. seizures with no discrete beginning or end, or period between seizures)
* Subjects who have a significant medical illness including kidney, liver, pulmonary, or gastrointestinal disease; or unstable or poorly controlled conditions such as hypertension, diabetes, or angina pectoris, as judged by the investigator.
* Have a clinically significant psychiatric illness as judged by the investigator
* Subjects who have had an active suicidal plan/intent or active suicidal thoughts, or suicide attempt as defined in the protocol
* Clinically significant laboratory abnormalities during the Screening Visit/Baseline Period, as judged by the investigator
* Subjects who have had serious adverse events (SAEs) thought to be related to study drug that led to discontinuation during Part A may not participate in Part B
* Active hepatitis B, hepatitis C, or human immunodeficiency virus
* Positive drug screen at screening or during the Baseline Period (excluding any allowed prescribed medications) and/or a history of alcoholism or drug addiction within past 2 years
* Subjects on felbamate with fewer than 18 month of continuous felbamate exposure at the time of the Screening Visit or with significant adverse reactions to felbamate
* Subjects treated with vigabatrin fewer than 2 years prior to the Screening Visit or who have a prior history of treatment with vigabatrin without a documented stable examination by an ophthalmologist as defined in the protocol
* Using prohibited medications or treated with any systemic immunosuppressant
* Have experienced a symptomatic viral, fungal, or bacterial infection requiring systemic treatment within 7 days prior to the first dose of study drug
* A current or prior history of illness precluding them from immunomodulatory therapy (e.g., history of recurrent infections)
* Have donated any blood or have had a significant loss of blood (500 mL) as defined in the protocol
* Have participated in any other clinical studies involving an investigational product or device and have received the last dose of the study drug associated with that clinical study within 30 days or 5 half-lives (whichever is longer) of the Screening Visit
* Have participated in earlier VX-765 clinical studies and received at least one dose of study drug
* Subjects who have no completed the full 13-week Treatment Period in part A may not participate in Part B
* Any subject judged by the investigator, sponsor or designee to be inappropriate for the study

Primary outcomes:
measure: Percent reduction in weekly seizure frequency during the Part A Late Treatment Period compared to the Part A Baseline Period
timeFrame: Up to 25 Weeks
measure: Percent of subjects with 50% or greater reduction in weekly seizure frequency (responder-rate) during the Part A Late Treatment Period compared to the Part A Baseline Period
timeFrame: Up to 25 Weeks
measure: Safety and tolerability as assessed by vital signs, standard 12-lead electrocardiograms (ECGs), laboratory assessments (serum chemistry, hematology, and urinalysis), and adverse events
timeFrame: Up to 56 Weeks
measure: Safety and tolerability as determined by vital signs, standard 12-lead electrocardiograms (ECGs), laboratory assessments (serum chemistry, hematology, and urinalysis) and adverse events
timeFrame: Up to 56 Weeks
Secondary outcomes:
measure: Percent of subjects who are seizure-free during the Part A Late Treatment Period
timeFrame: Up to 25 Weeks
measure: Percent reduction in seizure frequency during the entire Part A Treatment Period compared to the Part A Baseline Period
timeFrame: Up to 25 Weeks
measure: Percent of subjects with 50% or greater reduction in seizure frequency (responder-rate) during the entire Part A Treatment Period compared to the Part A Baseline Period
timeFrame: Up to 25 Weeks
measure: Percent of subjects who are seizure-free during the entire Part A Treatment Period
timeFrame: 13 Weeks
measure: Maximum number of consecutive days that subjects do not have seizures at any time during the Part A Late Treatment Period
timeFrame: Up to 13 Weeks
measure: Maximum number of consecutive days that subjects do not have seizures at any time during the entire Treatment Period
timeFrame: 13 Weeks
measure: Pharmacokinetics (e.g AUC, Cmax) of VX-765, VRT-043198, and concomitant antiepileptic drug (AED) levels in blood
timeFrame: Up to 21 Weeks
measure: Percent reduction in weekly seizure frequency compared to the Part A Baseline Period
timeFrame: Up to 56 Weeks
measure: Percent of subjects with 50% or greater reduction in weekly seizure frequency (50% responder-rate) during the entire Part B Treatment Period compared to the Part A Baseline Period
timeFrame: Up to 56 Weeks
measure: Percent of subjects with 75% or greater reduction in weekly seizure frequency (75% responder-rate) during the entire Part B Treatment Period compared to the Part A Baseline Period
timeFrame: Up to 56 Weeks
measure: Percent of subjects who are seizure-free during the entire Part B Treatment Period
timeFrame: Up to 28 Weeks
measure: Maximum number of consecutive days that subjects do not have seizures at any time during the entire Part B Treatment Period
timeFrame: Up to 28 Weeks
measure: Percent increase in weekly seizure-free days compared to the Part A Baseline Period
timeFrame: Up to 56 Weeks
Other outcomes:
Locations:
city: Northport
country: United States
facility: Alabama
state: Alabama
city: Phoenix
country: United States
facility: Arizona
state: Arizona
city: Phoenix
country: United States
facility: Arizon
state: Arizona
city: Little Rock
country: United States
facility: Arkansas
state: Arkansas
city: Loma Linda
country: United States
facility: California
state: California
city: Bradenton
country: United States
facility: Florida
state: Florida
city: Wellington
country: United States
facility: Florida
state: Florida
city: Boise
country: United States
facility: Idaho
state: Idaho
city: Baltimore
country: United States
facility: Maryland
state: Maryland
city: Farmington Hills
country: United States
facility: Michigan
state: Michigan
city: Saint Paul
country: United States
facility: Minnesota
state: Minnesota
city: Bronx
country: United States
facility: New York
state: New York
city: New York
country: United States
facility: New York
state: New York
city: Asheville
country: United States
facility: North Carolina
state: North Carolina
city: Charlotte
country: United States
facility: North Carolina
state: North Carolina
city: Columbus
country: United States
facility: Ohio
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma
state: Oklahoma
city: Philadelphia
country: United States
facility: Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: Texas
state: Texas
city: Orem
country: United States
facility: Utah
state: Utah
city: Charlottesville
country: United States
facility: Virginia
state: Virginia
city: Renton
country: United States
facility: Washington
state: Washington
city: Bonn
country: Germany
facility: Germany
city: Kork
country: Germany
facility: Germany
Study officials:
References: