Trial Outcomes & Findings for Verapamil as Therapy for Children and Young Adults With Dravet Syndrome (NCT NCT01607073)

Results Overview

The primary study endpoint is the change in number of seizures from baseline. Since we only had one participant finish the study, the endpoint was changed to Week 12 visit. Participants were on verapamil for 4 weeks at Week 12.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

2 participants

Primary outcome timeframe

Week 8 (baseline) to Week 12

Results posted on

2021-04-13

Participant Flow

One participant was recruited from the principal investigator's medical clinic. The other participant contacted us through clincialtrials.gov to participate in this study, and was subsequently recruited because he fit all inclusion/exclusion criteria.

Participant milestones

Participant milestones
Measure	Adjunctive Verapamil Participants taking verapamil for Dravet syndrome
Overall Study STARTED	2
Overall Study COMPLETED	1
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Adjunctive Verapamil Participants taking verapamil for Dravet syndrome
Overall Study Adverse Event	1

Baseline Characteristics

Verapamil as Therapy for Children and Young Adults With Dravet Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open Label Adjunctive Add on n=2 Participants open label adjunctive add on of verapamil to existing medications. dosing begins at 1 mg/kg/d and increases weekly to target of 4 mg/kg/d in divided doses (three times/day) Verapamil: Verapamil will be prepared as a solution. A 50mg/ml oral suspension may be made with immediate release tablets and either a 1:1 mixture of Ora-Sweet and Ora-Plus or a 1:1 mixture of Ora-Sweet SF and Ora-Plus will be used. Children will start on a 4 weeks titration period: Week 1: 1mg/kg/day divided BID Week 2: 2mg/kg/day divided BID or TID Week 3: 3mg/kg/day divided BID or TID Week 4: 4mg/kg/day divided TID In event of adverse events, and in consultation with the family and treating physician, the dosage may be decreased to 2mg/kg/day and remain at that dose for the remainder of the study.
Age, Categorical <=18 years	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	16.5 years STANDARD_DEVIATION 1.5 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 8 (baseline) to Week 12

Population: Change in number of general tonic-clonic seizures between Week 8 (baseline) and Week 12 visits.

The primary study endpoint is the change in number of seizures from baseline. Since we only had one participant finish the study, the endpoint was changed to Week 12 visit. Participants were on verapamil for 4 weeks at Week 12.

Outcome measures

Outcome measures
Measure	Week 8 Baseline n=2 Participants Week 8 visit - 8 weeks of baseline seizure data collected	Week 12 Verapamil 4mg/kg/Day n=2 Participants Participants have titrated up to 4mg/kg/day of verapamil
Change in Number of General Tonic-clonic Seizures From Week 8 (Baseline) Visit to Week 12 Visit	39 General tonic-clonic seizures	14 General tonic-clonic seizures

SECONDARY outcome

Timeframe: Week 8 (baseline) to Week 12

Population: Participant's collected number of myoclonic seizures at Week 8 visit (baseline) prior to taking verapamil and at Week 12 after 4 weeks of taking verapamil. This participant was the only participant who had seizure types other than general tonic-clonic seizures.

The secondary outcome is the change in number of myoclonic seizures between baseline Week 8 visit and Week 12 visit.

Outcome measures

Outcome measures
Measure	Week 8 Baseline n=1 Participants Week 8 visit - 8 weeks of baseline seizure data collected	Week 12 Verapamil 4mg/kg/Day n=1 Participants Participants have titrated up to 4mg/kg/day of verapamil
Change in Number of Myoclonic Seizures From Week 8 (Baseline) to Week 12	116 Myoclonic seizures	175 Myoclonic seizures

SECONDARY outcome

Timeframe: Week 8 to Week 12

Population: Number of Abscence seizures from Week 8 (baseline) to Week 12 visits.

The secondary outcome measure is the change in number of absence seizures from Week 8 (Baseline) to Week 12

Outcome measures

Outcome measures
Measure	Week 8 Baseline n=1 Participants Week 8 visit - 8 weeks of baseline seizure data collected	Week 12 Verapamil 4mg/kg/Day n=1 Participants Participants have titrated up to 4mg/kg/day of verapamil
Change in Number of Absence Seizures From Week 8 (Baseline) to Week 12	165 Abscence seizures	101 Abscence seizures

Adverse Events

Open Label Adjunctive Add on

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Open Label Adjunctive Add on n=2 participants at risk open label adjunctive add on of verapamil to existing medications. dosing begins at 1 mg/kg/d and increases weekly to target of 4 mg/kg/d in divided doses (three times/day) Verapamil: Verapamil will be prepared as a solution. A 50mg/ml oral suspension may be made with immediate release tablets and either a 1:1 mixture of Ora-Sweet and Ora-Plus or a 1:1 mixture of Ora-Sweet SF and Ora-Plus will be used. Children will start on a 4 weeks titration period: Week 1: 1mg/kg/day divided BID Week 2: 2mg/kg/day divided BID or TID Week 3: 3mg/kg/day divided BID or TID Week 4: 4mg/kg/day divided TID In event of adverse events, and in consultation with the family and treating physician, the dosage may be decreased to 2mg/kg/day and remain at that dose for the remainder of the study.
Nervous system disorders Seizure	50.0% 1/2 • Number of events 1 • Up to 35 weeks Adverse event data was collected from time of consent to end of study participation.

Other adverse events

Other adverse events
Measure	Open Label Adjunctive Add on n=2 participants at risk open label adjunctive add on of verapamil to existing medications. dosing begins at 1 mg/kg/d and increases weekly to target of 4 mg/kg/d in divided doses (three times/day) Verapamil: Verapamil will be prepared as a solution. A 50mg/ml oral suspension may be made with immediate release tablets and either a 1:1 mixture of Ora-Sweet and Ora-Plus or a 1:1 mixture of Ora-Sweet SF and Ora-Plus will be used. Children will start on a 4 weeks titration period: Week 1: 1mg/kg/day divided BID Week 2: 2mg/kg/day divided BID or TID Week 3: 3mg/kg/day divided BID or TID Week 4: 4mg/kg/day divided TID In event of adverse events, and in consultation with the family and treating physician, the dosage may be decreased to 2mg/kg/day and remain at that dose for the remainder of the study.
Nervous system disorders Insomnia	50.0% 1/2 • Number of events 1 • Up to 35 weeks Adverse event data was collected from time of consent to end of study participation.
Skin and subcutaneous tissue disorders Rash	50.0% 1/2 • Number of events 1 • Up to 35 weeks Adverse event data was collected from time of consent to end of study participation.
Nervous system disorders Drooling	50.0% 1/2 • Number of events 1 • Up to 35 weeks Adverse event data was collected from time of consent to end of study participation.

Additional Information

Beverly Wical, MD

Gillette Children's Specialty Healthcare

Phone: (651) 229-3870

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place