CompletedPhase 2

CX-8998 for Absence Seizures

United States7 participantsStarted 2018-02-25

Plain-language 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.

Who can participate

Age range16 Years – 55 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. 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.
✓. 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.
✓. 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).
✓. 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.
✓. 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.
✓. 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.
✓. Body weight ≥ 45 kg at screening.
✓. 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.

Exclusion criteria

✕. History of surgical intervention for treatment of epilepsy.
✕. 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.
✕. Inadequately treated psychotic or mood disorder (e.g., schizophrenia, major depression, bipolar disorder).
✕. 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.
✕. Presence of positive urine drug screen for drugs of abuse, except if this is explained by use of an allowed prescription medicine.
✕. Regular use of more than 2 standard drinks of alcohol per day (28 grams of pure alcohol).
✕. Hypersensitivity/allergic reaction to other T-type calcium agents, such as (but not limited to) ethosuximide and zonisamide.
✕. 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).

What they're measuring

Change From Baseline to End of Treatment in QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF)

Timeframe: Baseline (Day 1) to end of treatment 1-2 hours post-dose, up to 4 weeks post-dose.

Change From Baseline to End of Treatment in Clinical Alanine Aminotransferase Serum Chemistry Concentration

Timeframe: Baseline (Day 1) to end of treatment, or up to 4 weeks post-dose.

Change From Baseline to End of Treatment in Clinical Albumin Serum Chemistry Concentration

Timeframe: Baseline (Day 1) to end of treatment, or up to 4 weeks post-dose.

Change From Baseline to End of Treatment in Clinical Albumin/Globulin Serum Chemistry Concentration

Timeframe: Baseline (Day 1) to end of treatment, or up to 4 weeks post-dose.

Change From Baseline to End of Treatment in Clinical Alkaline Phosphatase Serum Chemistry Concentration

Timeframe: Baseline (Day 1) to end of treatment, or up to 4 weeks post-dose.

Change From Baseline to End of Treatment in Clinical Aspartate Aminotransferase Serum Chemistry Concentration

Timeframe: Baseline (Day 1) to end of treatment, or up to 4 weeks post-dose.

Trial details

NCT IDNCT03406702

SponsorJazz Pharmaceuticals

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2019-03-29

Results submitted2022-03-29

View on ClinicalTrials.gov More Epilepsy trials

Who can participate

Age range16 Years – 55 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. 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.
✓. 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.
✓. 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).
✓. 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.
✓. 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.
✓. 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.
✓. Body weight ≥ 45 kg at screening.
✓. 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.

Exclusion criteria

✕. History of surgical intervention for treatment of epilepsy.
✕. 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.
✕. Inadequately treated psychotic or mood disorder (e.g., schizophrenia, major depression, bipolar disorder).
✕. 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.
✕. Presence of positive urine drug screen for drugs of abuse, except if this is explained by use of an allowed prescription medicine.
✕. Regular use of more than 2 standard drinks of alcohol per day (28 grams of pure alcohol).
✕. Hypersensitivity/allergic reaction to other T-type calcium agents, such as (but not limited to) ethosuximide and zonisamide.
✕. 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).