A Study to Evaluate the Efficacy and Safety of VX-765 in Subjects With Treatment-Resistant Partial Epilepsy

Epilepsy Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01501383
• Other study ID #: VX11-765-402
• Status: Terminated
• Phase: Phase 2
• Start date: December 2011

Study information

• Verified date: September 2020
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 55
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• Epilepsies, Partial
• Epilepsy

Intervention

Drug:
• VX-765 Part A
Tablets of VX-765 given at different doses based on treatment group in Part A
• Placebo
Matching placebo
• VX-765 Part B
Tablets of VX-765 given at different doses based on patients who meet the study eligibility criteria for Part B

Locations

Country	Name	City	State
Germany	Germany	Bonn
Germany	Germany	Kork
United States	North Carolina	Asheville	North Carolina
United States	Maryland	Baltimore	Maryland
United States	Idaho	Boise	Idaho
United States	Florida	Bradenton	Florida
United States	New York	Bronx	New York
United States	North Carolina	Charlotte	North Carolina
United States	Virginia	Charlottesville	Virginia
United States	Ohio	Columbus	Ohio
United States	Texas	Dallas	Texas
United States	Michigan	Farmington Hills	Michigan
United States	Arkansas	Little Rock	Arkansas
United States	California	Loma Linda	California
United States	New York	New York	New York
United States	Alabama	Northport	Alabama
United States	Oklahoma	Oklahoma City	Oklahoma
United States	Utah	Orem	Utah
United States	Pennsylvania	Philadelphia	Pennsylvania
United States	Arizon	Phoenix	Arizona
United States	Arizona	Phoenix	Arizona
United States	Washington	Renton	Washington
United States	Minnesota	Saint Paul	Minnesota
United States	Florida	Wellington	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent reduction in weekly seizure frequency during the Part A Late Treatment Period compared to the Part A Baseline Period		Up to 25 Weeks
Primary	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		Up to 25 Weeks
Primary	Safety and tolerability as assessed by vital signs, standard 12-lead electrocardiograms (ECGs), laboratory assessments (serum chemistry, hematology, and urinalysis), and adverse events		Up to 56 Weeks
Primary	Safety and tolerability as determined by vital signs, standard 12-lead electrocardiograms (ECGs), laboratory assessments (serum chemistry, hematology, and urinalysis) and adverse events		Up to 56 Weeks
Secondary	Percent of subjects who are seizure-free during the Part A Late Treatment Period		Up to 25 Weeks
Secondary	Percent reduction in seizure frequency during the entire Part A Treatment Period compared to the Part A Baseline Period		Up to 25 Weeks
Secondary	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		Up to 25 Weeks
Secondary	Percent of subjects who are seizure-free during the entire Part A Treatment Period		13 Weeks
Secondary	Maximum number of consecutive days that subjects do not have seizures at any time during the Part A Late Treatment Period		Up to 13 Weeks
Secondary	Maximum number of consecutive days that subjects do not have seizures at any time during the entire Treatment Period		13 Weeks
Secondary	Pharmacokinetics (e.g AUC, Cmax) of VX-765, VRT-043198, and concomitant antiepileptic drug (AED) levels in blood		Up to 21 Weeks
Secondary	Percent reduction in weekly seizure frequency compared to the Part A Baseline Period		Up to 56 Weeks
Secondary	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		Up to 56 Weeks
Secondary	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		Up to 56 Weeks
Secondary	Percent of subjects who are seizure-free during the entire Part B Treatment Period		Up to 28 Weeks
Secondary	Maximum number of consecutive days that subjects do not have seizures at any time during the entire Part B Treatment Period		Up to 28 Weeks
Secondary	Percent increase in weekly seizure-free days compared to the Part A Baseline Period		Up to 56 Weeks