Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 4 of 4 for:    Epilepsy, Idiopathic Generalized 8

A Phase 2 Study of CX-8998 in Adolescents and Adults With Idiopathic Generalized Epilepsy With Absence Seizures (T-WAVE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03406702
Recruitment Status : Active, not recruiting
First Posted : January 23, 2018
Last Update Posted : May 10, 2019
Sponsor:
Information provided by (Responsible Party):
Cavion, Inc.

Brief Summary:
This is a Phase 2a, open-label study consisting of a screening period of up to 4 weeks and a 4-dose-titration treatment period to a dose of up to 10 mg twice daily (BID) of CX-8998, followed by a 1-week safety follow-up period after the last dose of study medication.

Condition or disease Intervention/treatment Phase
Epilepsy Drug: CX-8998 Phase 2

Detailed Description:

This is a Phase 2a, open-label study consisting of a screening period of up to 4 weeks and a 4-dose-titration treatment period to a dose of up to 10 mg twice daily (BID) of CX-8998, followed by a 1-week safety follow-up period after the last dose of study medication.

Subjects will participate for a total of up to 9 weeks, including screening, the 4-week treatment period and follow-up.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2a, Safety, Tolerability, Pharmacokinetics, and Quantitative EEG Study of CX-8998 in Adolescents and Adults With Idiopathic Generalized Epilepsy With Absence Seizures
Actual Study Start Date : February 25, 2018
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Epilepsy Seizures

Arm Intervention/treatment
Experimental: CX-8998
T-type calcium channel blocker
Drug: CX-8998
T-type calcium channel blocker




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] as assessed by CTCAE v4.0 [ Time Frame: Through study completion, an average of 9 weeks ]
    Treatment-emergent adverse events are all adverse events occurring during the treatment period or a pretreatment event that worsens in intensity during the treatment period.

  2. Changes from baseline in QTcF and other electrocardiogram parameters [ Time Frame: Baseline through study completion, an average of 5 weeks ]
    Fridericia's Correction Formula (QTCF) is a formula which takes into account the physiologic shortening of the QT interval which occurs as the heart rate increases, permitting comparison of the QT interval across a range of rates.

  3. Changes from baseline in clinical safety laboratory assessments [ Time Frame: Baseline through study completion, an average of 5 weeks ]
    Clinical safety laboratory assessments will include chemistry and hematology. Urinalysis to be performed only as clinically indicated. Additional lab tests are obtained at the screening visit to verify eligibility (including HIV, Hepatitis B and C).

  4. Number (%) of subjects who did not complete the study due to Treatment Emergent Adverse Events as assessed by CTCAE v4.0 [ Time Frame: Duration of study, an average of 9 weeks ]
    Treatment-emergent adverse events are all adverse events occurring during the treatment period or a pretreatment event that worsens in intensity during the treatment period.

  5. Number (%) of subjects with Serious Adverse Events as assessed by CTCAE v4.0 [ Time Frame: Duration of study, an average of 9 weeks ]
    Any adverse event that results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect observed in any offspring of the subject conceived during treatment with the study drug or is an important medical event.

  6. Number (%) of subjects with Adverse Events of Special Interest as assessed by CTCAE v4.0 [ Time Frame: Duration of study, an average of 9 weeks ]
    An adverse event of special interest is a serious adverse event as defined in Outcome 6. This includes, however is not limited to, increased seizure frequency, new seizure types, worsening of EEG parameters, systemic adverse events based on safety profile

  7. Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: The "lifetime" version of the C-SSRS will be used at screening, and the "since last visit" version at all other visits. The C-SSRS will be evaluated by the visiting nurse at Day 8 and Day 20 ]
    C-SSRS is a suicidal ideation rating scale which identifies behaviors that may be indicative of an individual's intent to commit suicide. The maximum suicidal ideation category (1-5 on the C-SSRS) present at the assessment.

  8. Epworth Sleepiness Scale (ESS) [ Time Frame: Duration of study, an average of 9 weeks ]
    The ESS is a scale intended to measure daytime sleepiness that is measured by use of a very short questionnaire asks the subject to rate his or her probability of falling asleep on a scale of increasing probability from 0 to 3 for 8 different situations. The scores are added together to obtain a single number.

  9. University of Miami Parkinson's Disease Hallucinations Questionnaire (UM-PDHQ) [ Time Frame: Duration of study, an average of 9 weeks ]
    The UM-PDHQ is a 20-item clinician-administered questionnaire that quantitatively and qualitatively assesses hallucinations. The UM-PDHQ will be completed for any subject who reports hallucinations



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   16 Years to 55 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed informed consent form (ICF) indicating that the subject has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts.
  2. Men or non-pregnant, non-breastfeeding women 16 to 55 years-of-age who are able to read and understand written and spoken local language.
  3. Clinical diagnosis of IGE (including, but not limited to, CAE, JAE, juvenile myoclonic epilepsy, or Jeavons syndrome) with absence seizures consistent with the International League against Epilepsy Revised Classification of Seizures (2017).
  4. Absence seizures persisting despite standard of care (SOC) treatment, defined as treatment with at least 2 AEDs appropriate for the patient's epilepsy syndrome. SOC failure, per investigator discretion, will be defined as insufficient clinical response or intolerable side effects, which precludes use of the appropriate AED.
  5. Observation of at least 3 instances of generalized discharges of approximately 2.5 - 4 Hz lasting ≥2 seconds via 24-hour ambulatory EEG (centrally reviewed), with approximately 75% normal background based on age and medication use per the central EEG reader's discretion. Intermittent focal spikes are allowed.
  6. On stable doses of one or more antiepileptic medication(s) for at least 30 days. If a subject is not on medication, adequate documentation justifying lack of therapy may be acceptable for the subject after sponsor review. Ketogenic, modified Atkins diet (MAD), or low glycemic diet with stable carbohydrate ratio for at least 30 days before screening is an acceptable antiepileptic therapy. Vagal nerve stimulation at stable settings (for at least 30 days before screening), without use of the magnet, is also acceptable.
  7. Body weight ≥ 45 kg at screening.
  8. Subjects with reproductive capability including all males and women of child-bearing potential (WOCBP) must agree to practice continuous abstinence or adequate contraception methods (appropriate double barrier method or oral, patch, implant, or injectable contraception) from as soon as feasible during screening period until at least 30 days after the last dose (i.e., intermittent abstinence based on "rhythm", temperature monitoring, or other means of timing is not acceptable). WOCBP include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, and/or bilateral oophorectomy) or is not post-menopausal. Post-menopausal is defined as amenorrhea ≥ 12 consecutive months without another cause, and a documented serum follicle stimulating hormone (FSH) level ≥ 35 mIU/mL.
  9. Male subjects with a partner of child-bearing potential must be surgically sterilized or be willing to use condoms with spermicide from as soon as feasible during screening period until at least 30 days after the last dose.
  10. Able and willing to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  11. Approval by the sponsor medical personnel or delegate as to final eligibility for the study.

Exclusion Criteria:

  1. History of surgical intervention for treatment of epilepsy.
  2. Additional seizure (clinical and electrographic) types, including, but not limited to, epileptic spasms, generalized tonic seizures, atonic seizures, or focal seizures. Subjects with GTCS or myoclonic seizures are eligible for the study.
  3. Inadequately treated psychotic or mood disorder (e.g., schizophrenia, major depression, bipolar disorder).
  4. Presence of severe intellectual disability, severe autism spectrum disorder, or severe developmental disorder such that the subject cannot sign the ICF or cannot cooperate with the study procedures.
  5. Presence of positive urine drug screen for drugs of abuse, except if this is explained by use of an allowed prescription medicine.
  6. Regular use of more than 2 standard drinks of alcohol per day (28 grams of pure alcohol).
  7. Hypersensitivity/allergic reaction to other T-type calcium agents, such as (but not limited to) ethosuximide and zonisamide.
  8. Use of strong CYP3A4 inhibitors, including prescription or non-prescription drugs or other products (i.e. grapefruit juice), which cannot be discontinued at least 2 weeks prior to Day 1 of dosing and throughout the study (Appendix C).
  9. Concurrent illnesses that would be a contraindication to trial participation, including, but not limited to:

    1. Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before screening
    2. NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled hypertension
    3. Clinically significant ECG abnormality per the Investigator assessment or any of the following: i) QTcF ≥450 msec (males) or ≥470 msec (females) ii) PR interval ≥250 msec iii) Atrioventricular block of second degree or higher, including Mobitz I iv) Persistent sinus bradycardia ≤ 50 beats per minute; persistent means the bradycardia is present on the first ECG and on one repeat ECG performed on another day v) For other ECG findings (e.g., including, but not necessarily limited to, tachycardia, bundle branch block, frequent ectopic beats, etc.) the Investigator should send a scanned, identity-blinded copy of the ECG tracing to the Study Safety Representative for review.
  10. Positive result for HIV, Hepatitis B [indicating ongoing infection], or Hepatitis C at screening or otherwise known ongoing infection with HIV, hepatitis B, or hepatitis C, unless curative therapy completed; for hepatitis C curative therapy is defined as negative PCR for HCV RNA.
  11. Significant hepatic (AST/ALT or bilirubin ≥ 2X upper limit of normal) or renal disease (creatinine clearance ≤39 mL/min) at screening.
  12. History of alcohol or substance abuse within the last year.
  13. A current C-SSRS score of 4 or 5 at screening or history of suicide attempt.
  14. Psychological, social, familial, or geographical reasons that would hinder or prevent compliance with the requirements of the protocol or compromise the informed consent process.
  15. Any other condition and/or situation that causes the Investigator or Study Safety Representative to deem a subject unsuitable for the study (including, but not limited to, expected study medication non-compliance, inability to medically tolerate the study procedures, or a subject's unwillingness to comply with study-related procedures).
  16. Treatment with an investigational agent within 30 days prior to the first dose of CX-8998 or planning to receive an investigational agent during the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03406702


Locations
Layout table for location information
United States, Arkansas
Arkansas Epilepsy Program
Little Rock, Arkansas, United States, 72205
United States, Florida
University of Florida
Tampa, Florida, United States, 33612
United States, Kentucky
Bluegrass Epilepsy Research, LLC
Lexington, Kentucky, United States, 40504
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
United States, New York
NYU Comprehensive Epilepsy Center
New York, New York, United States, 10016
United States, Ohio
Cincinnati Children's Hospital
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
Sponsors and Collaborators
Cavion, Inc.
Investigators
Layout table for investigator information
Study Director: Molly Myers Cavion, Inc.

Layout table for additonal information
Responsible Party: Cavion, Inc.
ClinicalTrials.gov Identifier: NCT03406702     History of Changes
Other Study ID Numbers: CX-8998-CLN2-002
First Posted: January 23, 2018    Key Record Dates
Last Update Posted: May 10, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Cavion, Inc.:
Epilepsy, Idiopathic Generalized Epilepsy, Absence Seizures

Additional relevant MeSH terms:
Layout table for MeSH terms
Epilepsy
Epilepsy, Generalized
Epilepsy, Absence
Epileptic Syndromes
Seizures
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs