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

This study has been terminated.
(Terminated by Sponsor)
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT01501383
First received: December 15, 2011
Last updated: January 15, 2014
Last verified: October 2012
  Purpose

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


Condition Intervention Phase
Epilepsy
Drug: VX-765 Part A
Drug: Placebo
Drug: VX-765 Part B
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • Percent reduction in weekly seizure frequency during the Part A Late Treatment Period compared to the Part A Baseline Period [ Time Frame: Up to 25 Weeks ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Up to 25 Weeks ] [ Designated as safety issue: No ]
  • Safety and tolerability as assessed by vital signs, standard 12-lead electrocardiograms (ECGs), laboratory assessments (serum chemistry, hematology, and urinalysis), and adverse events [ Time Frame: Up to 56 Weeks ] [ Designated as safety issue: Yes ]
  • Safety and tolerability as determined by vital signs, standard 12-lead electrocardiograms (ECGs), laboratory assessments (serum chemistry, hematology, and urinalysis) and adverse events [ Time Frame: Up to 56 Weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Percent of subjects who are seizure-free during the Part A Late Treatment Period [ Time Frame: Up to 25 Weeks ] [ Designated as safety issue: No ]
  • Percent reduction in seizure frequency during the entire Part A Treatment Period compared to the Part A Baseline Period [ Time Frame: Up to 25 Weeks ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Up to 25 Weeks ] [ Designated as safety issue: No ]
  • Percent of subjects who are seizure-free during the entire Part A Treatment Period [ Time Frame: 13 Weeks ] [ Designated as safety issue: No ]
  • Maximum number of consecutive days that subjects do not have seizures at any time during the Part A Late Treatment Period [ Time Frame: Up to 13 Weeks ] [ Designated as safety issue: No ]
  • Maximum number of consecutive days that subjects do not have seizures at any time during the entire Treatment Period [ Time Frame: 13 Weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics (e.g AUC, Cmax) of VX-765, VRT-043198, and concomitant antiepileptic drug (AED) levels in blood [ Time Frame: Up to 21 Weeks ] [ Designated as safety issue: No ]
  • Percent reduction in weekly seizure frequency compared to the Part A Baseline Period [ Time Frame: Up to 56 Weeks ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Up to 56 Weeks ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Up to 56 Weeks ] [ Designated as safety issue: No ]
  • Percent of subjects who are seizure-free during the entire Part B Treatment Period [ Time Frame: Up to 28 Weeks ] [ Designated as safety issue: No ]
  • Maximum number of consecutive days that subjects do not have seizures at any time during the entire Part B Treatment Period [ Time Frame: Up to 28 Weeks ] [ Designated as safety issue: No ]
  • Percent increase in weekly seizure-free days compared to the Part A Baseline Period [ Time Frame: Up to 56 Weeks ] [ Designated as safety issue: No ]

Enrollment: 55
Study Start Date: December 2011
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: VX-765 Dose 1 Part A Drug: VX-765 Part A
Tablets of VX-765 given at different doses based on treatment group in Part A
Active Comparator: VX-765 Dose 2 Part A Drug: VX-765 Part A
Tablets of VX-765 given at different doses based on treatment group in Part A
Active Comparator: VX-765 Dose 3 Part A Drug: VX-765 Part A
Tablets of VX-765 given at different doses based on treatment group in Part A
Active Comparator: VX-765 Dose 4 Part A Drug: VX-765 Part A
Tablets of VX-765 given at different doses based on treatment group in Part A
Placebo Comparator: Placebo Dose Part A
Placebo
Drug: Placebo
Matching placebo
Active Comparator: VX-765 Dose Part B Drug: VX-765 Part B
Tablets of VX-765 given at different doses based on patients who meet the study eligibility criteria for Part B

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01501383

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Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
  More Information

No publications provided

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01501383     History of Changes
Other Study ID Numbers: VX11-765-402
Study First Received: December 15, 2011
Last Updated: January 15, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Epilepsy
Epilepsies, Partial
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on October 01, 2014