Clinical Trial Results:
A Randomized, Double-blind, Placebo-controlled Trial to Investigate the Efficacy and Safety of Cannabidiol (CBD; GWP42003-P) in Infants with Infantile Spasms Following an Initial Open-label Pilot Study
Summary
|
|
EudraCT number |
2015-004904-50 |
Trial protocol |
PL |
Global end of trial date |
13 Jun 2019
|
Results information
|
|
Results version number |
v1 |
This version publication date |
29 Dec 2019
|
First version publication date |
29 Dec 2019
|
Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
GWEP15100
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
GW Research Ltd
|
||
Sponsor organisation address |
Sovereign House, Vision Park, Chivers Way, Histon, Cambridge, United Kingdom, CB24 9BZ
|
||
Public contact |
Medical Enquiries, GW Research Ltd, medinfo@gwpharm.com
|
||
Scientific contact |
Medical Enquiries, GW Research Ltd, medinfo@gwpharm.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
|
||
EMA paediatric investigation plan number(s) |
EMEA-001964-PIP01-16 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
13 Jun 2019
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
13 Jun 2019
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
13 Jun 2019
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
This study evaluated the efficacy and safety of CBD (GWP42003-P) in subjects with infantile spasms (IS) who have failed to become spasm free following treatment with 1 or more approved IS therapies.
|
||
Protection of trial subjects |
This trial was conducted in accordance with the ethical principles that have their origin in the World Medical Association (WMA) Declaration of Helsinki, adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and subsequent amendments. This trial was also designed to comply with ICH E6 Guideline for good clinical practice (EMA/CHMP/ICH/135/1995) and the European Clinical Trial Directive 2001/20/EC. The International Council for Harmonisation adopted guidelines and other relevant international guidelines, recommendations and requirements were taken into account as comprehensively as possible, as long as they did not violate Polish or US law.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 Apr 2017
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
United States: 8
|
||
Country: Number of subjects enrolled |
Poland: 1
|
||
Worldwide total number of subjects |
9
|
||
EEA total number of subjects |
1
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
9
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
|
|||||||||||||||
Recruitment
|
|||||||||||||||
Recruitment details |
- | ||||||||||||||
Pre-assignment
|
|||||||||||||||
Screening details |
Subjects were screened to assess their eligibility to enter the trial within 7 days prior to the first dose administration. | ||||||||||||||
Period 1
|
|||||||||||||||
Period 1 title |
Pilot
|
||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Non-randomised - controlled
|
||||||||||||||
Blinding used |
Not blinded | ||||||||||||||
Arms
|
|||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||
Arm title
|
Pilot, Cohort 1: GWP42003-P | ||||||||||||||
Arm description |
Subjects 6 month to 24 months of age received GWP42003-P for 14 days. Starting Day 1 and over the course of 4 days, subjects titrated up to a tolerable dose, not to exceed the target dose of 40 milligrams per kilogram per day (mg/kg/day) of GWP42003-P. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
GWP42003-P
|
||||||||||||||
Investigational medicinal product code |
GWP42003-P
|
||||||||||||||
Other name |
EPIDIOLEX, cannabidiol, CBD-OS
|
||||||||||||||
Pharmaceutical forms |
Oral solution
|
||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||
Dosage and administration details |
Subjects were administered GWP42003-P twice daily or three times daily if poorly tolerated. The dosage was split evenly across the two or three daily administrations to equal a total dose of 40mg/kg/day. Oral liquid formulation that is clear and colorless to yellow in appearance (100 mg/mL), in sesame oil with anhydrous ethanol added sweetener (sucralose) and strawberry flavoring. The oral liquid formulation was administered with a syringe.
|
||||||||||||||
Arm title
|
Pilot, Cohort 2: GWP42003-P | ||||||||||||||
Arm description |
Subjects 1 month to 24 months of age received GWP42003-P for 14 days. Starting Day 1 and over the course of 4 days, subjects titrated up to a tolerable dose, not to exceed the target dose of 40 milligrams per kilogram per day (mg/kg/day) of GWP42003-P. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
GWP42003-P
|
||||||||||||||
Investigational medicinal product code |
GWP42003-P
|
||||||||||||||
Other name |
EPIDIOLEX, cannabidiol, CBD-OS
|
||||||||||||||
Pharmaceutical forms |
Oral solution
|
||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||
Dosage and administration details |
Subjects were administered GWP42003-P, orally, twice daily or three times daily if poorly tolerated. The dosage was split evenly across the two or three daily administrations to equal the target or most tolerable dose. Oral liquid formulation that is clear and colorless to yellow in appearance (100 mg/mL), in sesame oil with anhydrous ethanol added sweetener (sucralose) and strawberry flavoring. The oral liquid formulation was administered with a syringe.
|
||||||||||||||
|
|||||||||||||||
Period 2
|
|||||||||||||||
Period 2 title |
Open Label Extension (OLE)
|
||||||||||||||
Is this the baseline period? |
No | ||||||||||||||
Allocation method |
Non-randomised - controlled
|
||||||||||||||
Blinding used |
Not blinded | ||||||||||||||
Arms
|
|||||||||||||||
Arm title
|
OLE: GWP42003-P | ||||||||||||||
Arm description |
Following completion of the pilot period, subjects were eligible to participate in the OLE period. Subjects continued their same dose administered in the pilot period for a maximum of 1 year and completed a 10 day taper after completing the study or withdrawing. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
GWP42003-P
|
||||||||||||||
Investigational medicinal product code |
GWP42003-P
|
||||||||||||||
Other name |
EPIDIOLEX, cannabidiol, CBD-OS
|
||||||||||||||
Pharmaceutical forms |
Oral solution
|
||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||
Dosage and administration details |
Subjects were administered GWP42003-P, orally, twice daily or three times daily if poorly tolerated. The dosage was split evenly across the two or three daily administrations to equal the target or most tolerable dose. Oral liquid formulation that is clear and colorless to yellow in appearance (100 mg/mL), in sesame oil with anhydrous ethanol added sweetener (sucralose) and strawberry flavoring. The oral liquid formulation was administered with a syringe.
|
||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Pilot
|
||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Pilot, Cohort 1: GWP42003-P
|
||
Reporting group description |
Subjects 6 month to 24 months of age received GWP42003-P for 14 days. Starting Day 1 and over the course of 4 days, subjects titrated up to a tolerable dose, not to exceed the target dose of 40 milligrams per kilogram per day (mg/kg/day) of GWP42003-P. | ||
Reporting group title |
Pilot, Cohort 2: GWP42003-P
|
||
Reporting group description |
Subjects 1 month to 24 months of age received GWP42003-P for 14 days. Starting Day 1 and over the course of 4 days, subjects titrated up to a tolerable dose, not to exceed the target dose of 40 milligrams per kilogram per day (mg/kg/day) of GWP42003-P. | ||
Reporting group title |
OLE: GWP42003-P
|
||
Reporting group description |
Following completion of the pilot period, subjects were eligible to participate in the OLE period. Subjects continued their same dose administered in the pilot period for a maximum of 1 year and completed a 10 day taper after completing the study or withdrawing. | ||
Subject analysis set title |
Pilot, All Subjects
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
This analysis set includes all subjects from both Cohort 1 and Cohort 2 in the Pilot Period.
|
|
||||||||||
End point title |
Pilot and OLE: Number of subjects with clinically significant electrocardiogram findings [1] | |||||||||
End point description |
Clinical significance was determined by the investigator. Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
|
|||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
Pilot, up to Day 15
OLE, up to Day 389
|
|||||||||
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No stat analysis conducted for this outcome measure. |
||||||||||
|
||||||||||
Notes [2] - Safety Analysis Set [3] - Safety Analysis Set |
||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Pilot and OLE: Number of subjects with clinically significant physical examination findings [4] | |||||||||
End point description |
Clinical significance was determined by the investigator. Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
|
|||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
Pilot, up to Day 15
OLE, up to Day 389
|
|||||||||
Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No stat analysis conducted for this outcome measure. |
||||||||||
|
||||||||||
Notes [5] - Safety Analysis Set [6] - Safety Analysis Set |
||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Pilot and OLE: Number of subjects with clinically significant vital sign findings [7] | |||||||||
End point description |
Clinical significance was determined by the investigator. Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
|
|||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
Pilot, up to Day 15
OLE, up to Day 389
|
|||||||||
Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No stat analysis conducted for this outcome measure. |
||||||||||
|
||||||||||
Notes [8] - Safety Analysis Set [9] - Safety Analysis Set |
||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Pilot and OLE: Number of subjects with severe treatment-emergent adverse events (TEAEs) [10] | |||||||||
End point description |
TEAEs are defined as AEs not present prior to the first investigational medicinal product (IMP) or placebo administration or any event already present that worsened in severity or frequency following IMP exposure. A TEAE occurred if the event was continuous from Baseline and was serious; IMP related; or resulted in death, discontinuation, interruption, or reduction of IMP. Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
|
|||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
Pilot, up to Day 15
OLE, up to Day 417
|
|||||||||
Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No stat analysis conducted for this outcome measure. |
||||||||||
|
||||||||||
Notes [11] - Safety Analysis Set [12] - Safety Analysis Set |
||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Pilot: Number of responders [13] | |||||||||
End point description |
A responder is defined as a subject experiencing a resolution of hypsarrhythmia and free of spasms. Testing for responders was conducted by video-electroencephalography (EEG) for at least 8 hours and up to 24 hours. Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
|
|||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
Pilot, Baseline to Day 15
|
|||||||||
Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No stat analysis conducted for this outcome measure. |
||||||||||
|
||||||||||
Notes [14] - Safety Analysis Set [15] - Safety Analysis Set |
||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Pilot: Percentage of responders [16] | ||||||||||||
End point description |
A responder is defined as a subject experiencing a resolution of hypsarrhythmia and free of spasms. Testing for responders was conducted by video-electroencephalography (EEG) for at least 8 hours and up to 24 hours. Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Pilot, Baseline to Day 15
|
||||||||||||
Notes [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No stat analysis conducted for this outcome measure. |
|||||||||||||
|
|||||||||||||
Notes [17] - Safety Analysis Set [18] - Safety Analysis Set |
|||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Pilot and OLE: Number of subjects with any low or high hematology laboratory parameter value [19] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
999=No analysis was conducted for this treatment arm at this time point.
n=number of subjects with evaluable data.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pilot, Day 1 to OLE, End of Taper, Day 389
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No stat analysis conducted for this outcome measure. |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [20] - Safety Analysis Set [21] - Safety Analysis Set |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Pilot and OLE: Number of subjects with any low or high biochemistry laboratory parameter value [22] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
999=No analysis was conducted for this treatment arm at this time point.
n=number of subjects with evaluable data.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pilot, Day 1 to OLE, End of Taper, Day 389
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No stat analysis conducted for this outcome measure. |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [23] - Safety Analysis Set [24] - Safety Analysis Set |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||
End point title |
Pilot and OLE: Number of subjects with any clinically relevant urinalysis parameter value [25] | ||||||||||||||||||||||||||||||||||||||||||
End point description |
Clinical significance was determined by the investigator. Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
999=No analysis was conducted for this treatment arm at this time point.
n=number of subjects with evaluable data.
|
||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pilot, Day 1 to OLE, End of Taper, Day 389
|
||||||||||||||||||||||||||||||||||||||||||
Notes [25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No stat analysis conducted for this outcome measure. |
|||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
Notes [26] - Safety Analysis Set [27] - Safety Analysis Set |
|||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Pilot and OLE: Number of subjects free of clinical spasms | ||||||||||||||||||||||||||||||
End point description |
Clinical spasms were determined by video-EEG for at least 8 hours and up to 24 hours. Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
999=No analysis was conducted for this treatment arm at this time point.
n=number of subjects with evaluable data.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Pilot, Day 1 to OLE, Day 379
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Notes [28] - Safety Analysis Set [29] - Safety Analysis Set |
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
End point title |
Pilot and OLE: Percentage of subjects free of clinical spasms | |||||||||||||||||||||||||||||||||
End point description |
Clinical spasms were determined by video-EEG for at least 8 hours and up to 24 hours. Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
999=No analysis was conducted for this treatment arm at this time point.
n=number of subjects with evaluable data.
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
Pilot, Day 1 to OLE, Day 379
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
Notes [30] - Safety Analysis Set [31] - Safety Analysis Set |
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Pilot and OLE: Number of subjects with a resolution of hypsarrhythmia | ||||||||||||||||||||||||||||||
End point description |
Resolution of hypsarrhythmia was determined by video-EEG for at least 8 hours and up to 24 hours. Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
999=No analysis was conducted for this treatment arm at this time point.
n=number of subjects with evaluable data.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Pilot: Day 1 to OLE, Day 379
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Notes [32] - Safety Analysis Set [33] - Safety Analysis Set |
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
End point title |
Pilot and OLE: Percentage of subjects with a resolution of hypsarrhythmia | |||||||||||||||||||||||||||||||||
End point description |
Resolution of hypsarrhythmia was determined by video-EEG for at least 8 hours and up to 24 hours. Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
999=No analysis was conducted for this treatment arm at this time point.
n=number of subjects with evaluable data.
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
Pilot, Day 1 to OLE, Day 379
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
Notes [34] - Safety Analysis Set [35] - Safety Analysis Set |
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Pilot and OLE: Number of subjects experiencing spasms and seizures subtypes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Caregivers recorded subject's spasms and seizures by category in a daily diary. Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
999=No analysis was conducted for this treatment arm at this time point.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pilot, Day 1 to OLE, Day 379
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [36] - Safety Analysis Set [37] - Safety Analysis Set |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Pilot and OLE: Average time to cessation of spasms | ||||||||||||
End point description |
Analysis could not be conducted for this end point. This study met No Go Criteria, in that all 9 patients enrolled in the pilot phase demonstrated continued hypsarrhythmia and spasms on follow-up video EEG after 2 weeks of treatment. The pilot period was terminated and the pivotal period was not initiated; however, all subjects completing the pilot period were eligible to roll into the OLE for a maximum of 1 year.
998=analysis could not be conducted
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Pilot, Day 1 to OLE, Day 379
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Pilot and OLE: Caregiver Global Impression of Change (CGIC) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The CGIC is a single question assessment completed by the caregiver. The question assesses the status of the subject's condition since they've started treatment. The caregiver provides a rating on a 7 point scale from 1-"very much improved" to 7-"very much worse". Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
999=No analysis was conducted for this treatment arm at this time point.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pilot, Day 1 to OLE, Day 379
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [38] - Safety Analysis Set [39] - Safety Analysis Set |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Pilot and OLE: Physician Global Impression of Change (PGIC) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The PGIC is a single question assessment completed by the investigator. The question assesses the status of the subject's condition since they've started treatment. The investigator provides a rating on a 7 point scale from 1-"very much improved" to 7-"very much worse". Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
999=No analysis was conducted for this treatment arm at this time point.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pilot, Day 1 to OLE, Day 379
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [40] - Safety Analysis Set [41] - Safety Analysis Set |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
OLE: Number of responders | ||||||||||||||||||
End point description |
A responder is defined as a subject experiencing a resolution of hypsarrhythmia and free of spasms. Testing for responders was conducted by video-electroencephalography (EEG) for at least 8 hours and up to 24 hours. Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
n=number of subjects with evaluable data.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
OLE, Day 16 to Day 379
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [42] - Safety Analysis Set |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
OLE: Percentage of responders | ||||||||||||||||||||
End point description |
A responder is defined as a subject experiencing a resolution of hypsarrhythmia and free of spasms. Testing for responders was conducted by video-electroencephalography (EEG) for at least 8 hours and up to 24 hours. Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
n=number of subjects with evaluable data.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
OLE, Day 16 to Day 379
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [43] - Safety Analysis Set |
|||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||
End point title |
OLE: Change from Baseline in height | |||||||||||||||||||||||||||||||||||||||
End point description |
A positive change indicates an increase in the average subject's height. A negative change indicates a decrease in the average subject's height. Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
999 = No analysis was conducted for this treatment arm at this time point.
CFB = Change from Baseline
|
|||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pilot, Baseline, Day 1 to OLE, End of Taper, Day 389
|
|||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
Notes [44] - Safety Analysis Set [45] - Safety Analysis Set |
||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||
End point title |
OLE: Change from Baseline in body weight | |||||||||||||||||||||||||||||||||||||||
End point description |
A positive change indicates an increase in the average subject's height. A negative change indicates a decrease in the average subject's height. Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
999 = No analysis was conducted for this treatment arm at this time point.
CFB=Change from Baseline
|
|||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pilot, Baseline, Day 1 to OLE, End of Taper, Day 389
|
|||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
Notes [46] - Safety Analysis Set [47] - Safety Analysis Set |
||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||
End point title |
OLE: Change from Baseline in head circumference | |||||||||||||||||||||||||||||||||||||||
End point description |
A positive change indicates an increase in the average subject's head circumference. A negative change indicates a decrease in the average subject's head circumference. Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
999 = No analysis was conducted for this treatment arm at this time point.
CFB=Change from Baseline
|
|||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pilot, Baseline, Day 1 to OLE, End of Taper, Day 389
|
|||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
Notes [48] - Safety Analysis Set [49] - Safety Analysis Set |
||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
OLE: Change from Baseline in Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) score | |||||||||||||||||||||
End point description |
The Vineland-II scores were assessed by the subject’s caregiver. Caregivers were asked to score questions in following categories the subject's communication, daily living, physical activity, problem behaviors, and social skills and relationships. Scoring was slightly different for each section, but generally ranged from "usually" to "never". Higher scores represent greater levels of functioning and lower skills represent lower levels of functioning. Analysis was conducted in members of the Safety Set, defined as all subjects who had received ≥ 1 dose of GWP42003-P.
n=number of subjects with evaluable data.
CFB=Change from Baseline
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Pilot, Baseline, Day 1 to OLE, Day 379
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Notes [50] - Safety Analysis Set [51] - Safety Analysis Set |
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||
End point title |
OLE: Number of subjects with relapse of spasms | ||||||
End point description |
Analysis could not be conducted for this end point. This study met No Go Criteria, in that all 9 patients enrolled in the pilot phase demonstrated continued hypsarrhythmia and spasms on follow-up video EEG after 2 weeks of treatment. The pilot period was terminated and the pivotal period was not initiated; however, all subjects completing the pilot period were eligible to roll into the OLE for a maximum of 1 year.
998=analysis could not be conducted
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
OLE Period, Day 16 to Day 379
|
||||||
|
|||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
OLE: Percentage of subjects with relapse of spasms | ||||||||
End point description |
Analysis could not be conducted for this end point. This study met No Go Criteria, in that all 9 patients enrolled in the pilot phase demonstrated continued hypsarrhythmia and spasms on follow-up video EEG after 2 weeks of treatment. The pilot period was terminated and the pivotal period was not initiated; however, all subjects completing the pilot period were eligible to roll into the OLE for a maximum of 1 year.
998=analysis could not be conducted
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
OLE Period, Day 16 to Day 379
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
OLE: Average time to relapse | ||||||||
End point description |
Analysis could not be conducted for this end point. This study met No Go Criteria, in that all 9 patients enrolled in the pilot phase demonstrated continued hypsarrhythmia and spasms on follow-up video EEG after 2 weeks of treatment. The pilot period was terminated and the pivotal period was not initiated; however, all subjects completing the pilot period were eligible to roll into the OLE for a maximum of 1 year.
998=analysis could not be conducted
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
OLE Period, Day 16 to Day 379
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Pilot, up to Day 15
OLE, up to Day 417
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Treatment-emergent adverse events (TEAEs) were collected in members of the Safety Population, comprised of all subjects who received at least 1 dose of GWP42003-P. TEAEs are defined as all adverse events not present prior to the first IMP or placebo administration or any event already present that worsened in severity or frequency following IMP.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Open Label Extension (OLE)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Pilot
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
31 May 2016 |
-Revised clinical phase and overall design;
-Addition of a pilot phase to confirm safety;
-Clarification of video-EEG evaluation;
-Clarification of cannabidiol metabolites;
-Duration of Open-label Extension Phase;
-Clarification of procedures following the investigator’s decision to discontinue GWP42003-P during the open label extension phase;
-Revised eligibility criteria;
-Clarification of withdrawal criterion;
-Revised pharmacokinetic blood sampling times;
-Removal of Caregiver Impression of IMP Palatability Questionnaire;
-Removal of THC testing. |
||
18 Oct 2016 |
-Extend age range in the pilot phase; second cohort;
-Clarification of allowable changes in concomitant medications;
-Utilization of central video electroencephalography readings;
-Changes to inclusion/exclusion criteria;
-Updated withdrawal criteria;
-Changes to information recorded in the paper diary;
-Updated statistical considerations. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
This study met No Go Criteria. Pilot Phase (PP) subjects had continued hypsarrhythmia/spasms after 2 weeks of treatment. The PP was terminated; the pivotal period was not initiated. Subjects completing the PP could roll into the OLE for up to 1 year. |