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

A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Efficacy, Safety, and Tolerability of Cannabidiol Oral Solution as Adjunctive Therapy With Vigabatrin as Initial Therapy in Patients With Infantile Spasms

The primary purpose of this study was to evaluate the efficacy, safety, and tolerability of Cannabidiol Oral Solution (CBD) as adjunctive therapy with vigabatrin as initial therapy, compared to vigabatrin alone in the treatment of infants newly diagnosed with Infantile Spasms (IS).

Study Overview

• Status: Terminated
• Conditions: Infantile Spasm
• Intervention / Treatment: Drug: Placebo; Drug: Cannabidiol Oral Solution; Drug: Vigabatrin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Beaumont Children's Hospital
  • Ohio
    • Akron, Ohio, United States, 44308
      • Akron Children's Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Washington
    • Tacoma, Washington, United States, 98405
      • Institute for Research and Innovation | MultiCare Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CBD with Vigabatrin; Participants received up to 40 milligrams per kilogram per day (mg/kg/day) divided twice daily (BID) of CBD with food. Participants also received up to 150 mg/kg/day BID of vigabatrin with food.	Drug: Cannabidiol Oral Solution; An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).; Drug: Vigabatrin; Powder suspension; Other Names: Sabril
Placebo Comparator: Placebo with Vigabatrin; Participants received a matching placebo to CBD with food, and also received up to 150 mg/kg/day BID of vigabatrin with food.	Drug: Placebo; Matching oral solution; Drug: Vigabatrin; Powder suspension; Other Names: Sabril

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Considered Complete Responders	Complete response is defined as complete resolution of spasms and hypsarrhythmia confirmed by 24-hour video-electroencephalogram (EEG).	Up to Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Resolution of Infantile Spasms	Resolution of IS was assessed by 24-hour video-EEG.	Up to Day 15
Percentage of Participants With Resolution of Hypsarrhythmia	Resolution of hypsarrhythmia was assessed by 24-hour video-EEG.	Up to Day 15
Investigator Impression of Efficacy and Tolerability of Study Drug Clinical Global Impression- Global Improvement (CGI-I)	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.	Day 15
Percentage of Participants With Increase in Number of Spasm-Free Days Between Day 1 and Day 15	Increase in spasm-free days will be determined by seizure diary entries.	Up to Day 15
Percentage of Participants With Complete Response During the Initial Treatment Period Who Relapse During the Extended Treatment Period	Relapse during the extended treatment period will be confirmed by video-EEG following parent report of relapse.	Up to Day 75
Time to Relapse During the Extended Treatment Period		Up to Day 75

Collaborators and Investigators

• Sponsor: Radius Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2018
• Primary Completion (Actual): May 29, 2019
• Study Completion (Actual): May 29, 2019

Study Registration Dates

• First Submitted: January 26, 2018
• First Submitted That Met QC Criteria: February 1, 2018
• First Posted (Actual): February 5, 2018

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: May 11, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Cannabidiol oral solution; Vigabatrin; Infantile spasm
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epileptic Syndromes; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Epilepsy; Spasms, Infantile; Spasm; Muscle Cramp; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; GABA Agents; Anticonvulsants; Cannabidiol; Vigabatrin
• Other Study ID Numbers: INS011-16-082

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No