Trial Outcomes & Findings for A Study of GWP42003 as Adjunctive Therapy in the First Line Treatment of Schizophrenia or Related Psychotic Disorder (NCT NCT02006628)
NCT ID: NCT02006628
Last Updated: 2022-09-28
Results Overview
The percentage of PANSS treatment responders, defined as participants with ≥20% improvement in PANSS Total score between baseline and End of Treatment, is presented. The percentage of participants was calculated by dividing the number of participants with a ≥20% improvement in PANSS Total score (yes) by the total number of participants.
COMPLETED
PHASE2
88 participants
Day 1 through Day 43
2022-09-28
Participant Flow
Participant milestones
| Measure |
GWP42003 1000 Milligram (mg)/Day
Participants received GWP42003 (100 mg/milliliter \[mL\]), 5 mL twice daily (BID) administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
Placebo
Participants received placebo (0 mL cannabidiol \[CBD\]), volume matched to the 5 mL BID dose level, administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
43
|
45
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
43
|
45
|
|
Overall Study
Intention to Treat (ITT) Analysis Set
|
42
|
44
|
|
Overall Study
COMPLETED
|
40
|
43
|
|
Overall Study
NOT COMPLETED
|
3
|
2
|
Reasons for withdrawal
| Measure |
GWP42003 1000 Milligram (mg)/Day
Participants received GWP42003 (100 mg/milliliter \[mL\]), 5 mL twice daily (BID) administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
Placebo
Participants received placebo (0 mL cannabidiol \[CBD\]), volume matched to the 5 mL BID dose level, administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
Baseline Characteristics
A Study of GWP42003 as Adjunctive Therapy in the First Line Treatment of Schizophrenia or Related Psychotic Disorder
Baseline characteristics by cohort
| Measure |
GWP42003 1000 mg/Day
n=43 Participants
Participants received GWP42003 (100 mg/mL), 5 mL BID administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
Placebo
n=45 Participants
Participants received placebo (0 mL CBD), volume matched to the 5 mL BID dose level, administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
Total
n=88 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
40.9 years
STANDARD_DEVIATION 12.49 • n=99 Participants
|
40.8 years
STANDARD_DEVIATION 11.00 • n=107 Participants
|
40.8 years
STANDARD_DEVIATION 11.69 • n=206 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=99 Participants
|
22 Participants
n=107 Participants
|
37 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
51 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Day 1 through Day 43Population: ITT analysis set: all participants who provided informed consent, were randomized to 1 of the treatment groups, took at least 1 dose of IMP, and had post-baseline efficacy data. One placebo participant with a PANSS Total score \<60 at Day 1 and 1 GWP42003 participant with no post-baseline efficacy data were excluded from the ITT analysis set.
The PANSS was a 30-item medical scale completed by a trained rater that assessed the positive and negative symptoms of schizophrenia as well as symptoms of general psychopathology. The PANSS Total score was derived from the sum of the 30 items, which were rated on a 7-point scale, where 1 = absent and 7 = extreme. The total score is the summed total for each of the PANSS positive symptom ('P'), negative symptom ('N'), general psychopathology symptom ('G') scores and could range from 30 to 210 points, with lower scores equating to milder severity of symptoms, that is, closer to psychologically normal.
Outcome measures
| Measure |
GWP42003 1000 mg/Day
n=42 Participants
Participants received GWP42003 (100 mg/mL), 5 mL BID administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
Placebo
n=44 Participants
Participants received placebo (0 mL CBD), volume matched to the 5 mL BID dose level, administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
|---|---|---|
|
Change From Baseline To End Of Treatment (Day 43) In Positive And Negative Syndrome Scale (PANSS) Total Score
Baseline score
|
79.3 score on a scale
Standard Deviation 12.45
|
80.6 score on a scale
Standard Deviation 14.90
|
|
Change From Baseline To End Of Treatment (Day 43) In Positive And Negative Syndrome Scale (PANSS) Total Score
End of Treatment score
|
68.1 score on a scale
Standard Deviation 14.79
|
71.9 score on a scale
Standard Deviation 15.49
|
|
Change From Baseline To End Of Treatment (Day 43) In Positive And Negative Syndrome Scale (PANSS) Total Score
Change from baseline
|
-11.2 score on a scale
Standard Deviation 7.87
|
-8.8 score on a scale
Standard Deviation 8.87
|
PRIMARY outcome
Timeframe: Day 1 through Day 43Population: ITT analysis set: all participants who provided informed consent, were randomized to 1 of the treatment groups, took at least 1 dose of IMP, and had post-baseline efficacy data. One placebo participant with a PANSS Total score \<60 at Day 1 and 1 GWP42003 participant with no post-baseline efficacy data were excluded from the ITT analysis set.
The percentage of PANSS treatment responders, defined as participants with ≥20% improvement in PANSS Total score between baseline and End of Treatment, is presented. The percentage of participants was calculated by dividing the number of participants with a ≥20% improvement in PANSS Total score (yes) by the total number of participants.
Outcome measures
| Measure |
GWP42003 1000 mg/Day
n=42 Participants
Participants received GWP42003 (100 mg/mL), 5 mL BID administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
Placebo
n=44 Participants
Participants received placebo (0 mL CBD), volume matched to the 5 mL BID dose level, administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
|---|---|---|
|
Percentage Of PANSS Total Score Responders At End Of Treatment (Day 43)
No
|
30 Participants
|
38 Participants
|
|
Percentage Of PANSS Total Score Responders At End Of Treatment (Day 43)
Yes
|
12 Participants
|
6 Participants
|
PRIMARY outcome
Timeframe: Day 1 through Day 43Population: ITT analysis set: all participants who provided informed consent, were randomized to 1 of the treatment groups, took at least 1 dose of IMP, and had post-baseline efficacy data. One placebo participant with a PANSS Total score \<60 at Day 1 and 1 GWP42003 participant with no post-baseline efficacy data were excluded from the ITT analysis set.
The PANSS 'P' scale measured the severity of positive symptoms, including delusions, conceptual disorganization, hallucinations, hyperactivity, grandiosity, suspiciousness/persecution, and hostility. Individual items were rated on a 7-point scale, where 1 = absent and 7 = extreme. The total 'P' score could range from 7 to 49 points, with lower scores equating to milder severity of symptoms, that is, closer to psychologically normal.
Outcome measures
| Measure |
GWP42003 1000 mg/Day
n=42 Participants
Participants received GWP42003 (100 mg/mL), 5 mL BID administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
Placebo
n=44 Participants
Participants received placebo (0 mL CBD), volume matched to the 5 mL BID dose level, administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
|---|---|---|
|
Change From Baseline To The End Of Treatment (Day 43) In PANSS 'P' Score
Change from Baseline
|
-3.2 score on a scale
Standard Deviation 2.60
|
-1.7 score on a scale
Standard Deviation 2.76
|
|
Change From Baseline To The End Of Treatment (Day 43) In PANSS 'P' Score
Baseline score
|
18.0 score on a scale
Standard Deviation 3.89
|
17.5 score on a scale
Standard Deviation 3.29
|
|
Change From Baseline To The End Of Treatment (Day 43) In PANSS 'P' Score
End of Treatment score
|
14.8 score on a scale
Standard Deviation 4.01
|
15.7 score on a scale
Standard Deviation 3.73
|
PRIMARY outcome
Timeframe: Day 1 through Day 43Population: ITT analysis set: all participants who provided informed consent, were randomized to 1 of the treatment groups, took at least 1 dose of IMP, and had post-baseline efficacy data. One placebo participant with a PANSS Total score \<60 at Day 1 and 1 GWP42003 participant with no post-baseline efficacy data were excluded from the ITT analysis set.
The PANSS 'N' scale measured the severity of negative symptoms, including blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking. Individual items were rated on a 7-point scale, where 1 = absent and 7 = extreme. The total 'N' score could range from 7 to 49 points, with lower scores equating to milder severity of symptoms, that is, closer to psychologically normal.
Outcome measures
| Measure |
GWP42003 1000 mg/Day
n=42 Participants
Participants received GWP42003 (100 mg/mL), 5 mL BID administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
Placebo
n=44 Participants
Participants received placebo (0 mL CBD), volume matched to the 5 mL BID dose level, administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
|---|---|---|
|
Change From Baseline To The End Of Treatment (Day 43) In PANSS 'N' Score
Baseline score
|
22.6 score on a scale
Standard Deviation 5.04
|
23.4 score on a scale
Standard Deviation 5.11
|
|
Change From Baseline To The End Of Treatment (Day 43) In PANSS 'N' Score
End of Treatment score
|
19.9 score on a scale
Standard Deviation 5.32
|
20.5 score on a scale
Standard Deviation 5.22
|
|
Change From Baseline To The End Of Treatment (Day 43) In PANSS 'N' Score
Change from Baseline
|
-2.7 score on a scale
Standard Deviation 3.55
|
-2.9 score on a scale
Standard Deviation 3.06
|
PRIMARY outcome
Timeframe: Day 1 through Day 43Population: ITT analysis set: all participants who provided informed consent, were randomized to 1 of the treatment groups, took at least 1 dose of IMP, and had post-baseline efficacy data. One placebo participant with a PANSS Total score \<60 at Day 1 and 1 GWP42003 participant with no post-baseline efficacy data were excluded from the ITT analysis set.
The PANSS 'G' scale measured the severity of general psychopathology symptoms, including somatic concern, anxiety, guilt feelings, tension, mannerisms and posturing, depression, motor retardation, uncooperativeness, unusual thought content, disorientation, poor attention, lack of judgement and insight, disturbance of violation, poor impulse control, preoccupation, and active social avoidance. Individual items were rated on a 7-point scale, where 1 = absent and 7 = extreme. The total 'G' score could range from 16 to 112 points, with lower scores equating to milder severity of symptoms, that is, closer to psychologically normal.
Outcome measures
| Measure |
GWP42003 1000 mg/Day
n=42 Participants
Participants received GWP42003 (100 mg/mL), 5 mL BID administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
Placebo
n=44 Participants
Participants received placebo (0 mL CBD), volume matched to the 5 mL BID dose level, administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
|---|---|---|
|
Change From Baseline To The End Of Treatment (Day 43) In PANSS 'G' Score
Baseline score
|
38.7 score on a scale
Standard Deviation 6.71
|
39.7 score on a scale
Standard Deviation 8.95
|
|
Change From Baseline To The End Of Treatment (Day 43) In PANSS 'G' Score
End of Treatment score
|
33.4 score on a scale
Standard Deviation 7.69
|
35.6 score on a scale
Standard Deviation 9.04
|
|
Change From Baseline To The End Of Treatment (Day 43) In PANSS 'G' Score
Change from Baseline
|
-5.3 score on a scale
Standard Deviation 4.34
|
-4.1 score on a scale
Standard Deviation 4.78
|
PRIMARY outcome
Timeframe: Day 1 through Day 43Population: ITT analysis set: all participants who provided informed consent, were randomized to 1 of the treatment groups, took at least 1 dose of IMP, and had post-baseline efficacy data. One placebo participant with a PANSS Total score \<60 at Day 1 and 1 GWP42003 participant with no post-baseline efficacy data were excluded from the ITT analysis set.
The SANS assessed 5 symptom complexes to obtain clinical ratings of negative symptoms in participants with schizophrenia or related psychotic disorder. Symptom complexes were affective blunting, alogia (impoverished thinking), avolition/apathy, anhedonia/asociality, and disturbance of attention. Assessments were conducted on a 6-point scale (0 = not at all; 5 = severe). The total score could range from 0 to 125 points, with lower scores equating to milder severity of symptoms, that is, closer to psychologically normal.
Outcome measures
| Measure |
GWP42003 1000 mg/Day
n=42 Participants
Participants received GWP42003 (100 mg/mL), 5 mL BID administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
Placebo
n=44 Participants
Participants received placebo (0 mL CBD), volume matched to the 5 mL BID dose level, administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
|---|---|---|
|
Change From Baseline To The End Of Treatment (Day 43) In The Scale For The Assessment Of Negative Symptoms (SANS)
Baseline score
|
52.8 score on a scale
Standard Deviation 17.10
|
55.3 score on a scale
Standard Deviation 16.24
|
|
Change From Baseline To The End Of Treatment (Day 43) In The Scale For The Assessment Of Negative Symptoms (SANS)
End of Treatment score
|
43.6 score on a scale
Standard Deviation 16.54
|
48.4 score on a scale
Standard Deviation 15.75
|
|
Change From Baseline To The End Of Treatment (Day 43) In The Scale For The Assessment Of Negative Symptoms (SANS)
Change from Baseline
|
-9.1 score on a scale
Standard Deviation 13.09
|
-6.3 score on a scale
Standard Deviation 8.54
|
PRIMARY outcome
Timeframe: Day 1 through Day 43Population: ITT analysis set: all participants who provided informed consent, were randomized to 1 of the treatment groups, took at least 1 dose of IMP, and had post-baseline efficacy data. One placebo participant with a PANSS Total score \<60 at Day 1 and 1 GWP42003 participant with no post-baseline efficacy data were excluded from the ITT analysis set.
The CGI-S was a 7-point scale that required the clinician to rate the severity of a participant's illness at the time of assessment, relative to the clinician's past experience of participants who had the same diagnosis. Considering total clinical experience, participants were assessed on severity of mental illness at the time of rating on the following scale: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; or 7 = extremely ill. Lower scores equated to milder severity of symptoms, that is, closer to psychologically normal.
Outcome measures
| Measure |
GWP42003 1000 mg/Day
n=42 Participants
Participants received GWP42003 (100 mg/mL), 5 mL BID administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
Placebo
n=44 Participants
Participants received placebo (0 mL CBD), volume matched to the 5 mL BID dose level, administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
|---|---|---|
|
Change From Baseline To The End Of Treatment (Day 43) In The Clinical Global Impression Severity Scale (CGI-S)
Baseline score
|
4.0 score on a scale
Standard Deviation 0.70
|
4.0 score on a scale
Standard Deviation 0.65
|
|
Change From Baseline To The End Of Treatment (Day 43) In The Clinical Global Impression Severity Scale (CGI-S)
End of Treatment score
|
3.5 score on a scale
Standard Deviation 1.09
|
3.8 score on a scale
Standard Deviation 0.78
|
|
Change From Baseline To The End Of Treatment (Day 43) In The Clinical Global Impression Severity Scale (CGI-S)
Change from Baseline
|
-0.5 score on a scale
Standard Deviation 0.74
|
-0.3 score on a scale
Standard Deviation 0.49
|
PRIMARY outcome
Timeframe: Day 8 through Day 43Population: ITT analysis set: all participants who provided informed consent, were randomized to 1 of the treatment groups, took at least 1 dose of IMP, and had post-baseline efficacy data. One placebo participant with a PANSS Total score \<60 at Day 1 and 1 GWP42003 participant with no post-baseline efficacy data were excluded from the ITT analysis set.
The CGI-I was a 7-point scale that required the clinician to assess how much a participant's illness had improved or worsened relative the first assessment at the beginning of the intervention. This was rated on the following scale: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; or 7 = very much worse. Lower scores equated to improvement of symptoms.
Outcome measures
| Measure |
GWP42003 1000 mg/Day
n=42 Participants
Participants received GWP42003 (100 mg/mL), 5 mL BID administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
Placebo
n=44 Participants
Participants received placebo (0 mL CBD), volume matched to the 5 mL BID dose level, administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
|---|---|---|
|
Clinical Global Impression Improvement Scale (CGI-I) Values At Day 8 And End Of Treatment (Day 43)
End of Treatment score
|
2.9 score on a scale
Standard Deviation 0.89
|
3.4 score on a scale
Standard Deviation 0.87
|
|
Clinical Global Impression Improvement Scale (CGI-I) Values At Day 8 And End Of Treatment (Day 43)
Day 8 score
|
3.6 score on a scale
Standard Deviation 0.50
|
3.8 score on a scale
Standard Deviation 0.56
|
PRIMARY outcome
Timeframe: Day 1 through Day 43Population: ITT analysis set: all participants who provided informed consent, were randomized to 1 of the treatment groups, took at least 1 dose of IMP, and had post-baseline efficacy data. One placebo participant with a PANSS Total score \<60 at Day 1 and 1 GWP42003 participant with no post-baseline efficacy data were excluded from the ITT analysis set.
The BACS was an instrument used to assess the aspects of cognition found to be most impaired and most strongly correlated with outcome in participants with schizophrenia or related psychotic disorder. The BACS consisted of 6 domains: verbal memory (score range 0 to 75), working memory (score range 0 to 28), motor speed (score range 0 to 100), verbal fluency (score \> 0, with no set maximum value), attention and speed of information processing (score range 0 to 110), and executive functions (score range 0 to 22). A score was obtained for each of the 6 domains. A composite summary score was then calculated as the arithmetic mean of the unweighted scores from the 6 domains. While there was not an upper limit on the composite score, overall, an increase in score was indicative of an improvement in cognition.
Outcome measures
| Measure |
GWP42003 1000 mg/Day
n=42 Participants
Participants received GWP42003 (100 mg/mL), 5 mL BID administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
Placebo
n=44 Participants
Participants received placebo (0 mL CBD), volume matched to the 5 mL BID dose level, administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
|---|---|---|
|
Change From Baseline To The End Of Treatment (Day 43) In Brief Assessment Of Cognition In Schizophrenia (BACS) Score
End of Treatment score
|
35.73 score on a scale
Standard Deviation 6.981
|
35.05 score on a scale
Standard Deviation 7.310
|
|
Change From Baseline To The End Of Treatment (Day 43) In Brief Assessment Of Cognition In Schizophrenia (BACS) Score
Change from Baseline
|
3.48 score on a scale
Standard Deviation 3.031
|
2.14 score on a scale
Standard Deviation 3.442
|
|
Change From Baseline To The End Of Treatment (Day 43) In Brief Assessment Of Cognition In Schizophrenia (BACS) Score
Baseline score
|
32.21 score on a scale
Standard Deviation 6.042
|
32.91 score on a scale
Standard Deviation 7.158
|
Adverse Events
GWP42003 1000 mg/Day
Placebo
Serious adverse events
| Measure |
GWP42003 1000 mg/Day
n=43 participants at risk
Participants received GWP42003 (100 mg/mL), 5 mL BID administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
Placebo
n=45 participants at risk
Participants received placebo (0 mL CBD), volume matched to the 5 mL BID dose level, administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
|---|---|---|
|
Psychiatric disorders
Schizophrenia
|
0.00%
0/43 • Day 1 through Day 57
Safety analysis set: all participants who provided informed consent, were randomized to treatment, and took at least 1 dose of IMP.
|
2.2%
1/45 • Day 1 through Day 57
Safety analysis set: all participants who provided informed consent, were randomized to treatment, and took at least 1 dose of IMP.
|
Other adverse events
| Measure |
GWP42003 1000 mg/Day
n=43 participants at risk
Participants received GWP42003 (100 mg/mL), 5 mL BID administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
Placebo
n=45 participants at risk
Participants received placebo (0 mL CBD), volume matched to the 5 mL BID dose level, administered orally, 5 mL in the morning and 5 mL in the evening for 6 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
9.3%
4/43 • Day 1 through Day 57
Safety analysis set: all participants who provided informed consent, were randomized to treatment, and took at least 1 dose of IMP.
|
4.4%
2/45 • Day 1 through Day 57
Safety analysis set: all participants who provided informed consent, were randomized to treatment, and took at least 1 dose of IMP.
|
|
Gastrointestinal disorders
Nausea
|
7.0%
3/43 • Day 1 through Day 57
Safety analysis set: all participants who provided informed consent, were randomized to treatment, and took at least 1 dose of IMP.
|
0.00%
0/45 • Day 1 through Day 57
Safety analysis set: all participants who provided informed consent, were randomized to treatment, and took at least 1 dose of IMP.
|
|
Nervous system disorders
Headache
|
7.0%
3/43 • Day 1 through Day 57
Safety analysis set: all participants who provided informed consent, were randomized to treatment, and took at least 1 dose of IMP.
|
8.9%
4/45 • Day 1 through Day 57
Safety analysis set: all participants who provided informed consent, were randomized to treatment, and took at least 1 dose of IMP.
|
|
Nervous system disorders
Somnolence
|
0.00%
0/43 • Day 1 through Day 57
Safety analysis set: all participants who provided informed consent, were randomized to treatment, and took at least 1 dose of IMP.
|
6.7%
3/45 • Day 1 through Day 57
Safety analysis set: all participants who provided informed consent, were randomized to treatment, and took at least 1 dose of IMP.
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/43 • Day 1 through Day 57
Safety analysis set: all participants who provided informed consent, were randomized to treatment, and took at least 1 dose of IMP.
|
4.4%
2/45 • Day 1 through Day 57
Safety analysis set: all participants who provided informed consent, were randomized to treatment, and took at least 1 dose of IMP.
|
Additional Information
Medical Enquires
GW Research Ltd
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60