Study to Evaluate the Effect of GWP42003 on Liver Fat Levels in Participants With Fatty Liver Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of GWP42003 on liver triglyceride (liver fat) in participants with fatty liver disease (FLD).

Detailed Description
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This study was conducted as a 10-week (eight-week treatment period and one-week safety follow-up), randomized, partially-blind study that evaluated the effect of GWP42003 in participants with raised liver triglycerides (liver fat ≥5%). Participants were clinically diagnosed with FLD and had liver fat levels ≥5% as measured by Magnetic Resonance Imaging/ Magnetic Resonance Scanning (MRI/MRS), or were willing to undergo MRI/MRS scan at the screening visit to confirm a liver fat content of ≥5%. Eligible participants entered the study at a screening visit (Day -10 to -2) and then returned for a fasted baseline visit (Day 1), a mid-treatment visit (Day 29) and an end of treatment visit (Day 57). Safety follow-up telephone calls took place throughout the treatment period up to Day 64 after completion of treatment or seven days after date of last dose/withdrawal.

Official Title
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A Randomised, Partially-blind, Placebo-controlled, Pilot, Dose-ranging Study To Assess The Effect Of Cannabidiol (CBD) On Liver Fat Levels In Subjects With Fatty Liver Disease.

Conditions
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Fatty Liver

Intervention / Treatment
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* Drug: GWP42003 200 mg/day Dose
* Drug: GWP42003 400 mg/day Dose
* Drug: GWP42003 800 mg/day Dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant gave informed consent for participation in the study. Participant was aged 18 years or above. Participant had documented evidence of liver fat content ≥5% as measured by MRI/MRS scanning or a biopsy within two months prior to screening, or willing to undergo an MRI/MRS scan at Visit 1 (Day -10 to -2) to confirm a liver fat content of ≥5%. Participant had, in the opinion of the investigator, no changes in levels of exercise or diet for four weeks (as assessed by the physical activity questionnaire and food frequency questionnaire) prior to the start of treatment, and participant agreed to keep stable for the duration of the study. Participant was able (in the investigator's opinion) and willing to comply with all study requirements. Participant was willing for his or her name to be notified to the responsible authorities for participation in this study, as applicable. Participant was willing to allow his or her primary care practitioner and consultant, if appropriate, to be notified of participation in the study. Exclusion Criteria: Participant had clinical diagnosis or treatment for Type I/II diabetes. Participant had received an unapproved investigational medicinal product (IMP) within the 30 days prior to the screening visit. Participant was receiving a prohibited medication and unwilling to stop for 14 days prior to the screening visit and for the duration of the study. Participant was using or had used recreational cannabis, medicinal cannabis, or cannabinoid medications (including Sativex) within one month prior to study entry and unwilling to abstain for the duration of the study. Participant had any known or suspected history of alcohol or substance abuse, or epilepsy or recurrent seizures. Participant had any known or suspected history of major depression sufficient to require treatment or disrupt ordinary life (excluding episodes of reactive depression, in the opinion of the investigator). Participant had clinically significant cardiac, renal, or hepatic impairment, in the opinion of the investigator. Participant had known history of Hepatitis B or C. Participant had genetic dyslipidaemia, in the opinion of the Investigator. Participant had any other significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, influence the result of the study, or affect the participant's ability to participate in the study. Participant had any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP(s). Participant had presence of any metal implants. Participant had any known or suspected history of claustrophobia. Female participants of child bearing potential not able or willing to use effective contraception for the duration of the study and for three months thereafter, or male participants whose partner was of child bearing potential, who was not willing to ensure that they or their partner would use effective contraception during the study and for three months thereafter. Female participant who was pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter. Participants who weighed >150 kilograms (kg). Participant had any abnormalities following a physical examination that, in the opinion of the investigator, prevented the participant from safe participation in the study. Participant was unwilling to abstain from donation of blood during the study. Participant had planned travel outside the country of residence during the study. Participant had previously enrolled into this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GWP42003 200 milligrams (mg)/day Dose<br>Participants self-administered one x 100 mg GWP42003 capsule twice daily for 8 weeks (the first dose was 30 minutes before breakfast [fasted] and the second was 30 minutes before the evening meal [typically 12 hours apart]). | Drug: GWP42003 200 mg/day Dose<br>* GWP42003 was presented as Licaps® size double zero (Size 00) hard gelatin capsules containing 100 mg of CBD dissolved in vehicle (Gelucire 44/14).<br>* Other names: Cannabidiol, CBD;|
| Experimental: GWP42003 400 mg/day Dose<br>Participants self-administered two x 100 mg GWP42003 capsules twice daily for 8 weeks (the first dose was 30 minutes before breakfast [fasted] and the second was 30 minutes before the evening meal [typically 12 hours apart]). | Drug: GWP42003 400 mg/day Dose<br>* GWP42003 was presented as Licaps® Size 00 hard gelatin capsules containing 100 mg of CBD dissolved in vehicle (Gelucire 44/14).<br>* Other names: Cannabidiol, CBD;|
| Experimental: GWP42003 800 mg/day Dose<br>Participants self-administered four x 100 mg GWP42003 capsules twice daily for 8 weeks (the first dose was 30 minutes before breakfast [fasted] and the second was 30 minutes before the evening meal [typically 12 hours apart]). | Drug: GWP42003 800 mg/day Dose<br>* GWP42003 was presented as Licaps® Size 00 hard gelatin capsules containing 100 mg of CBD dissolved in vehicle (Gelucire 44/14).<br>* Other names: Cannabidiol, CBD;|
| Experimental: Placebo<br>Participants self-administered one, two or four placebo capsules twice daily, for 8 weeks (the first dose was 30 minutes before breakfast [fasted] and the second was 30 minutes before the evening meal [typically 12 hours apart]). Each capsule exactly matched the GWP42003 capsules in terms of appearance, size, smell and taste. | Drug: Placebo<br>* Placebo was presented as Licaps® Size 00 hard gelatin capsules containing excipients (Gelucire 44/14).<br>* Other names: Placebo control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline To The End Of Treatment (EOT) In Mean Liver Triglyceride Levels | Liver triglyceride levels were measured by Magnetic Resonance Imaging/Magnetic Resonance Scanning and the percent change from baseline to EOT in group mean levels was investigated. A reduction from baseline, that is, a negative value, indicates an improvement in condition. | Baseline to EOT (Day 57) or Early Termination (ET) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline To The EOT In Mean Serum Total Cholesterol Levels | A fasting blood sample was taken for the measurement of serum total cholesterol. A reduction from baseline, that is, a negative value, indicates an improvement in condition. | Baseline to EOT (Day 57) or ET | 
| Change From Baseline To The EOT In Mean Serum High Density Lipoprotein (HDL)-Cholesterol(C) Levels | A fasting blood sample was obtained for the measurement of HDL-C. An increase from baseline, that is, a positive value, indicates an improvement in condition. | Baseline to EOT (Day 57) or ET | 
| Change From Baseline To The EOT In Mean Serum Low-Density Lipoprotein (LDL)-C Levels | A fasting blood sample was obtained for the measurement of LDL-C. An increase from baseline, that is, a positive value, indicates an improvement in condition. | Baseline to EOT (Day 57) or ET | 
| Change From Baseline To The EOT In Mean Serum HDL: Low Density Lipoprotein (LDL)-Cholesterol (C) Ratio | A fasting blood sample was obtained for the measurement of HDL-C and LDL-C, allowing the HDL:LDL cholesterol ratio to be calculated. An increase from baseline, that is, a positive value, indicates an improvement in condition. | Baseline to EOT (Day 57) or ET | 
| Change From Baseline To The EOT In Mean Serum Triglyceride Levels | A fasting blood sample was obtained for the measurement of serum triglycerides. A reduction from baseline, that is, a negative value, indicates an improvement in condition. | Baseline to EOT (Day 57) or ET | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cannabidiol, Fatty liver, Diabetes, Body fat