Fenfluramine for Infantile Spasms

Recruiting at 2 trial locations

Overseen By Virginia Allhusen, PhD

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Los Angeles

Must be taking: ACTH, Vigabatrin

Must not be taking: Cannabinoids

Disqualifiers: Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase II clinical trial in which children with refractory infantile spasms (also called epileptic spasms or West syndrome) will be treated with fenfluramine, to evaluate efficacy, safety, and tolerability. Patients with infantile spasms that have not responded to treatment with vigabatrin and ACTH we will be invited to participate. Study participants will undergo baseline video-EEG, receive treatment with fenfluramine for 21 days, and then undergo repeat video-EEG to determine effectiveness. Patients with favorable response will have the opportunity to continue treatment for up to 6 months.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot start or change doses of second-line treatments for infantile spasms within 14 days before the trial. Also, you should not have used any cannabinoid products in the 14 days before the trial.

What makes the drug Fenfluramine unique for treating infantile spasms?

Fenfluramine is unique because it has been used in other conditions as a central stimulant with fewer side effects and lower abuse potential compared to other stimulants, which may offer a safer option for treating infantile spasms. ^{1 2 3 4 5}

Research Team

Daniel Shrey, MD

Principal Investigator

Children's Hospital of Orange County

Eligibility Criteria

This trial is for children aged 1 to 3 with infantile spasms that haven't improved after treatment with ACTH and vigabatrin. Kids can't join if they have serious heart problems, used cannabinoids recently, started a new spasm treatment or diet, or got a vagal nerve stimulator in the last few weeks.

Inclusion Criteria

My child is between 1 and 3 years old.

My child has been diagnosed with infantile spasms.

My seizures have not stopped despite treatment with ACTH and vigabatrin.

Exclusion Criteria

You started and kept on a ketogenic diet within 3 months before the screening.

I had a vagal nerve stimulator implanted within the last 14 days.

You have used any products containing cannabinoids in the two weeks before screening.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fenfluramine treatment for 21 days, with dosage titrated to 0.8 mg/kg/day

3 weeks

Baseline and post-treatment video-EEG visits

Extension

Participants with favorable response may continue treatment for up to 6 months

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Fenfluramine

Trial Overview The study tests fenfluramine's effectiveness and safety in treating stubborn infantile spasms. Over three weeks, kids will take the drug and have two video-EEGs before and after to see if it works. Responders may continue for six months.

Participant Groups

Group I: Fenfluramine treatment Experimental Treatment 1 Intervention

Open label treatment with fenfluramine. Dosage will be titrated to 0.8 mg/kg/day, for an initial duration of 21 days. Patients with favorable response will have an option to continue treatment for up to 6 months.

Fenfluramine is already approved in United States, European Union for the following indications:

Approved in United States as Fintepla for:

• Seizures associated with Dravet syndrome
• Seizures associated with Lennox-Gastaut syndrome

Approved in European Union as Fintepla for:

• Seizures associated with Dravet syndrome
• Seizures associated with Lennox-Gastaut syndrome

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Children's Hospital of Orange County

Lead Sponsor

Trials

38

Recruited

5,700+

Findings from Research

Fenetylline (CAPTAGON) has been used therapeutically for over 23 years, particularly in treating hyperkinetic children, and is considered to have a more favorable benefit/risk profile compared to traditional amphetamines.

It exhibits fewer adverse side effects and a lower potential for abuse, making it a safer alternative among central stimulants, although prescription status should be regulated by national authorities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fenetylline: therapeutic use, misuse and/or abuse. Kristen, G., Schaefer, A., von Schlichtegroll, A.[2019]

In a study involving 77 children aged 3 weeks to 12 years, fenoldopam effectively reduced blood pressure during surgery at doses of 0.8 to 3.2 mcg/kg/min, demonstrating its potential for safe use in pediatric patients.

The effective dosing range for fenoldopam in children is significantly higher than that for adults, indicating that tailored dosing is necessary for pediatric patients undergoing anesthesia, while the drug was well-tolerated with minimal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics And Pharmacodynamics Of Fenoldopam Mesylate For Blood Pressure Control In Pediatric Patients. Hammer, GB., Verghese, ST., Drover, DR., et al.[2018]

Lisdexamfetamine is a newly approved prodrug for treating ADHD in children aged 6-12, which is converted to active dextroamphetamine in the body, providing a similar therapeutic effect to traditional stimulants.

This medication has a lower potential for abuse compared to conventional stimulants, as it does not produce high levels of dextroamphetamine when misused, making it a safer option for young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lisdexamfetamine dimesylate for childhood ADHD. Madaan, V.[2017]

Captagon, a psychostimulant drug, is still being illicitly produced and traded, particularly in Southeast Europe and Asia, with links to terrorist organizations like ISIS, highlighting a significant public health and security concern.

The study found that while traditional e-commerce platforms showed limited results for Captagon sales, the Dark web provided substantial data on its availability, indicating a need for more comprehensive research methods to address the issue of psychoactive drugs in conflict zones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Captagon: use and trade in the Middle East. Al-Imam, A., Santacroce, R., Roman-Urrestarazu, A., et al.[2022]

A study involving 24 healthy Chinese male volunteers found that the capsule formulation of meclofenoxate hydrochloride is bioequivalent to the tablet formulation, meaning they are absorbed in the body at similar rates and extents after a single 200-mg dose.

Both formulations were well tolerated with no adverse events reported, indicating a good safety profile for meclofenoxate hydrochloride in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence and pharmacokinetic comparison of a single 200-mg dose of meclofenoxate hydrochloride capsule and tablet formulations in healthy Chinese adult male volunteers: a randomized sequence, open-label, two-period crossover study. Zou, JJ., Ji, HJ., Wu, DW., et al.[2022]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Fenetylline: therapeutic use, misuse and/or abuse. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics And Pharmacodynamics Of Fenoldopam Mesylate For Blood Pressure Control In Pediatric Patients. [2018]

3. Spain pubmed.ncbi.nlm.nih.gov

Lisdexamfetamine dimesylate for childhood ADHD. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Captagon: use and trade in the Middle East. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Bioequivalence and pharmacokinetic comparison of a single 200-mg dose of meclofenoxate hydrochloride capsule and tablet formulations in healthy Chinese adult male volunteers: a randomized sequence, open-label, two-period crossover study. [2022]