CX-8998 for Absence Seizures

NCT ID: NCT03406702

Last Updated: 2022-09-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-25
• Study Completion Date: 2019-03-29

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.

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.

Conditions

Epilepsy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CX-8998

T-type calcium channel blocker

Group Type: EXPERIMENTAL

CX-8998

Intervention Type: DRUG

T-type calcium channel blocker

Interventions

CX-8998

T-type calcium channel blocker

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jazz Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Arkansas Epilepsy Program

Little Rock, Arkansas, United States

University of Florida

Tampa, Florida, United States

Bluegrass Epilepsy Research, LLC

Lexington, Kentucky, United States

Tufts Medical Center

Boston, Massachusetts, United States

NYU Comprehensive Epilepsy Center

New York, New York, United States

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CX-8998-CLN2-002

Identifier Type: -

Identifier Source: org_study_id