A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms

This was a randomized, double-blind, placebo-controlled, parallel-group study in which participants were randomized in a 1:1 ratio to 1 of 2 treatment groups. During the Initial Treatment Period, participants received either vigabatrin plus CBD or vigabatrin plus matching placebo and were dosed approximately every 12 hours, with a meal. This study was comprised of five periods: Screening, Initial Treatment, Extended Treatment, Taper, and Follow up Periods, with a maximum duration of approximately 140 days.

• Cannabidiol Oral Solution (Drug): An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).
• Placebo (Drug): Matching oral solution
• Vigabatrin (Drug), also known as Sabril: Powder suspension

Primary outcomes

• Percentage of Participants Considered Complete Responders [Up to Day 15]: Complete response is defined as complete resolution of spasms and hypsarrhythmia confirmed by 24-hour video-electroencephalogram (EEG).

Secondary outcomes

• Percentage of Participants With Resolution of Infantile Spasms [Up to Day 15]: Resolution of IS was assessed by 24-hour video-EEG.
• Percentage of Participants With Resolution of Hypsarrhythmia [Up to Day 15]: Resolution of hypsarrhythmia was assessed by 24-hour video-EEG.
• Investigator Impression of Efficacy and Tolerability of Study Drug Clinical Global Impression- Global Improvement (CGI-I) [Day 15]: Investigators will use the CGI-I scale, which is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention and is rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. Higher scores indicated worse condition.
• Percentage of Participants With Increase in Number of Spasm-Free Days Between Day 1 and Day 15 [Up to Day 15]: Increase in spasm-free days will be determined by seizure diary entries.
• Percentage of Participants With Complete Response During the Initial Treatment Period Who Relapse During the Extended Treatment Period [Up to Day 75]: Relapse during the extended treatment period will be confirmed by video-EEG following parent report of relapse.
• Time to Relapse During the Extended Treatment Period [Up to Day 75]

Sex: All, ages: 1 Month to 24 Months

Inclusion Criteria:

1. Parent(s)/caregiver(s) fully comprehends and signs the informed consent form, understands all study procedures, and can communicate satisfactorily with the Investigator and study coordinator, in accordance with applicable laws, regulations, and local requirements.
2. Clinical diagnosis of Infantile Spasms, confirmed by video-EEG (including at least one cluster of electroclinical spasms \[≥3 in any 10-minute epoch\] and hypsarrythmia) obtained during the Screening Period and read by a central reader.
3. General good health (defined as the absence of any clinically relevant abnormalities as determined by the Investigator) based on physical and neurological examinations, medical history, and clinical laboratory values completed during the Screening Visit).
4. In the opinion of the investigator, the parent(s)/caregiver(s) is (are) willing and able to comply with the study procedures and visit schedules.

Exclusion Criteria:

1. Is considered by the investigator, for any reason (including, but not limited to, the risks described as precautions, warnings, and contraindications in the current version of the Investigator's Brochure for Cannabidiol Oral Solution) to be an unsuitable candidate to receive the study drug.
2. Known or suspected allergy to cannabidiol.
3. History of an allergic reaction or a known or suspected sensitivity to any substance that is contained in the investigational product formulation.
4. Use of any cannabidiol/cannabis product within 30 days of study entry.
5. Participant is diagnosed or suspected of having tuberous sclerosis.
6. Participant has received treatment with either vigabatrin, ACTH, or high-dose steroids previously.
7. Previous or concomitant therapy with felbamate, clobazam, valproic acid, or the ketogenic diet.
8. Participant currently on any disallowed CYP3A4-related medication (phenytoin, fluvoxamine, carbamazepine, and St. John's Wort).
9. Previously received any investigational drug or device or investigational therapy within 30 days before Screening.
10. Clinically significant abnormal laboratory values, including: liver function tests (LFTs) such as albumin, direct bilirubin, total bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≥3 times the upper limit of normal (ULN). The investigator may deem the participant eligible if he or she judges the laboratory values to be not clinically significant.

Participant flow

Outcome results

• Percentage of Participants Considered Complete Responders (Primary)
• Percentage of Participants With Resolution of Infantile Spasms (Secondary)
• Percentage of Participants With Resolution of Hypsarrhythmia (Secondary)
• Investigator Impression of Efficacy and Tolerability of Study Drug Clinical Global Impression- Global Improvement (CGI-I) (Secondary)
• Percentage of Participants With Increase in Number of Spasm-Free Days Between Day 1 and Day 15 (Secondary)
• Percentage of Participants With Complete Response During the Initial Treatment Period Who Relapse During the Extended Treatment Period (Secondary)
• Time to Relapse During the Extended Treatment Period (Secondary)

Adverse events

Time frame: This study was terminated by the Sponsor. The Sponsor terminated the study due to slow enrollment and a failure to identify adequate participants that met eligibility criteria. Due to study termination and only 2 participants being enrolled there are concerns regarding participant confidentiality, therefore no data are being reported.

Limitations and caveats: This study was terminated by the Sponsor. The Sponsor terminated the study due to slow enrollment and a failure to identify adequate participants that met eligibility criteria. Due to study termination and only 2 participants being enrolled there are concerns regarding participant confidentiality, therefore no data are being reported.

• Study Protocol (PDF, 2018-07-10)
• Statistical Analysis Plan (PDF, 2017-10-30)