Clinical trial NCT01562314: A Pilot Study of GWP42003 in the Symptomatic Treatment of Ulcerative Colitis (GWID10160)
Official title: A Randomised, Double-blind, Placebo-controlled Parallel Group, Pilot Study of GWP42003 in the Symptomatic Treatment of Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ulcerative Colitis
Keywords: Mild to Moderate Ulcerative Colitis
GWP42003
Lead sponsor: GWResearch
Sponsor class: UNKNOWN
First posted: 2012-03-23
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was conducted to determine the efficacy and safety of GWP42003 compared with placebo by the percentage of participants achieving remission quantified as a Mayo score of 2 or less (with no sub-score \>1) after 10 weeks of treatment.

Detailed description: This study was conducted by GW Research Ltd as a pilot study to determine the efficacy and safety of GWP42003 (50 milligram \[mg\] up to 250 mg twice daily \[BID\]), compared with placebo, as assessed by the percentage of participants achieving remission quantified as a Mayo score of 2 or less (with no sub-score \>1) after 10 weeks of treatment. This was the first study to determine whether the study drug has a positive benefit for participants on their ulcerative colitis symptom control, as well as effects on inflammatory marker cytokines (C reactive protein \[CRP\]), a fecal inflammatory marker (calprotectin), stool frequency, and rectal bleeding. In addition, various inflammatory bowel disease (IBD) questionnaires were implemented in the study to observe further benefits on the study drug, compared with placebo.

This study was multi-center, randomized, double-blind, placebo-controlled, and parallel-group. The study consisted of a 7-day baseline period, a 10-week treatment period, and a 1-week follow-up period. Each participant had a Mayo assessment (including endoscopy) conducted to confirm eligibility. Eligible participants were randomized in a 1:1 ratio into the GWP42003 and placebo groups. At the start of the treatment period, participants entered a 2-week dose escalation period to achieve their maximum tolerated dose, up to 250 mg BID in the GWP42003 group. Participants remained at the maximum tolerated dose for the rest of the treatment period.

Eligibility criteria: Inclusion Criteria:

* Male or female participants aged 18 years or above;
* Participant diagnosed with mild to moderate ulcerative colitis and on a fixed dose of 5-Aminosalicylic (5-ASA) treatment and have been on a stable dose for at least 2 weeks prior to screening (0 mg dose of 5-ASA was acceptable);
* Participants at screening and baseline with a Mayo assessment score of greater than or equal to 4 (≥4) but less than or equal to 10 (≤10) and with an endoscopy score of at least 1 (≥1) , following an adequate exposure to oral and/ or topical 5-ASA, in the opinion of the investigator;
* In the opinion of the investigator, capable of complying with the study requirements and completing the study;
* Willing and able to give informed consent;
* Willing for his or her name to be notified to the responsible authorities for participation in this study, as applicable;
* Willing to allow his or her primary care practitioner and consultant, if appropriate, to be notified of participation in the study;

Exclusion Criteria:

* Severe ulcerative colitis (Mayo score of greater than 10 (\>10);
* Ulcerative colitis only affecting the rectum (proctitis)
* Gastrointestinal infection evident from stool culture and testing for Clostridium difficile toxin (in the opinion of the investigator);
* Currently using or had used recreational cannabis, medicinal cannabis, cannabinoid medications (including Sativex®), or synthetic cannabinoid-based medications within 1 month prior to study entry and unwilling to abstain for the duration of the study;
* Any known or suspected history of alcohol or substance abuse, epilepsy or recurrent seizures, or hypersensitivity to cannabinoids;
* Was receiving a prohibited medication prior to screening and for the duration of the study;
* Previous non-responders to mono or polyclonal anti-Tumor Necrosis Factor antibodies;
* Personal or first degree relative, with history of schizophrenia or other psychosis;
* History of other significant psychiatric disorder or severe personality disorder (at the discretion of the investigator);
* Any known or suspected history of depression sufficient to require treatment with antidepressants or disrupt ordinary life (excluding episodes of reactive depression at the discretion of the investigator);
* Clinically significant cardiac, renal or hepatic impairment in the opinion of the investigator;
* Female participants who were pregnant, lactating or planning pregnancy during the course of the study and for 3 months from the date of last dose;
* Female participants of child bearing potential, unless willing to use 2 forms of contraception, 1 of which must have been a barrier contraception (for example, a female condom or occlusive cap \[diaphragm or cervical vault/caps\] with spermicide) during the study and for 3 months from the date of last dose (however a male condom should not have been used in conjunction with the female condom);
* Male participants whose partner was of child bearing potential, unless willing to use an appropriate barrier method of contraception (condom and spermicide) in addition to having their female partner use another form of barrier contraception (for example, an occlusive cap \[diaphragm or cervical vault/caps\] with spermicide) during the study and for 3 months from date of last dose (however a male condom should not have been used in conjunction with a female condom);
* Planned to travel outside the country of residence during the treatment phase of the study;
* Received an Investigational Medicinal Product (IMP) within 30 days prior to the screening visit;
* In the opinion of the investigator, was not considered to be suitable for the study;
* Any other significant disease or disorder which, in the opinion of the investigator, may either have put the participant at risk because of participation in the study, or may have influenced the result of the study or the participant's ability to participate in the study;
* Participant with any abnormalities that, in the opinion of the investigator, would prevent the participant from safe participation in the study;
* Unwilling to abstain from donation of blood during the study;
* Participants previously randomized into this study.

Primary outcomes:
measure: Number Of Participants With A Mayo Score Of 2 Or Less (With No Sub-score >1) At EOT
timeFrame: Baseline to End of Treatment (EOT) (10 weeks) or Early Termination (ET)
measure: Number Of Participants With A Mayo Score Of 2 Or Less (With No Sub-score >1) At EOT - PP Analysis
timeFrame: Baseline to EOT (10 weeks) or ET
Secondary outcomes:
measure: Distribution On The PGAS At EOT
timeFrame: EOT (10 weeks) or ET
measure: Distribution On The PGAS At EOT - PP Analysis
timeFrame: EOT (10 weeks) or ET
measure: Change From Baseline To EOT In The PGAS Score
timeFrame: Baseline to EOT (10 weeks) or ET
measure: Change From Baseline To EOT In The PGAS Score - PP Analysis
timeFrame: Baseline to EOT (10 weeks) or ET
measure: Change From Baseline To EOT In The Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score
timeFrame: Baseline to EOT (10 weeks) or ET
measure: Change From Baseline To EOT In The IBDQ Total Score - PP Analysis
timeFrame: Baseline to EOT (10 weeks) or ET
measure: Number Of Participants Who Reported An Improvement In The Subject Global Impression Of Change (SGIC) Questionnaire At EOT
timeFrame: Visit 4 (Day 43) to EOT (10 weeks) or ET
measure: Number Of Participants Who Reported An Improvement In The SGIC Questionnaire At EOT - PP Analysis
timeFrame: Visit 4 (Day 43) to EOT (10 weeks) or ET
measure: Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Stool Frequency Numerical Rating Scale (NRS)
timeFrame: Baseline to EOT (last 7 days) or ET
measure: Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Stool Frequency NRS - PP Analysis
timeFrame: Baseline to EOT (last 7 days) or ET
measure: Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Rectal Bleeding NRS
timeFrame: Baseline to EOT (last 7 days) or ET
measure: Change From Baseline To The Last Week Of Treatment In Ulcerative Colitis Symptoms, As Measured By Scores On The Rectal Bleeding NRS - PP Analysis
timeFrame: Baseline to EOT (last 7 days) or ET
measure: Change From Baseline To EOT In The Mayo Total Score
timeFrame: Baseline to EOT (10 weeks) or ET
measure: Change From Baseline To EOT In The Mayo Partial Score
timeFrame: Baseline to EOT (10 weeks) or ET
measure: Change From Baseline To EOT In Levels Of Fecal Calprotectin
timeFrame: Baseline to EOT (10 weeks) or ET
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
city: Coventry
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Middlesex
country: United Kingdom
city: Wigan
country: United Kingdom
Study officials:
References:
citation: Irving PM, Iqbal T, Nwokolo C, Subramanian S, Bloom S, Prasad N, Hart A, Murray C, Lindsay JO, Taylor A, Barron R, Wright S. A Randomized, Double-blind, Placebo-controlled, Parallel-group, Pilot Study of Cannabidiol-rich Botanical Extract in the Symptomatic Treatment of Ulcerative Colitis. Inflamm Bowel Dis. 2018 Mar 19;24(4):714-724. doi: 10.1093/ibd/izy002.