E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of 2, 5 and 15 mg twice daily of GWP42004 compared with placebo by assessing the impact of treatment on glycaemic control in the treatment of participants with Type 2 diabetes. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of 2, 5 and 15 mg twice daily of GWP42004 compared with placebo on:
• Other measures of glycaemic control
• Measures of insulin sensitivity
• Measures of beta cell function
• Body weight
• Body Mass Index (BMI)
• Lipid parameters
• A marker of inflammation
• Cardiovascular parameters
• Health economics
To assess the safety and tolerability of GWP42004 compared with placebo on:
• Adverse Events (AEs)
• Vital signs
• Depression (Beck Depression Inventory-II [BDI-II])
• Suicidal tendencies (Columbia-Suicide Severity Rating Scale [C-SSRS])
• Electrocardiogram (ECG)
• Clinical pathology (haematology and clinical chemistry)
• Physical examination
• Blood glucose safety (Self-Monitoring of Blood Glucose [SMBG])
• Cannabis withdrawal (Cannabis Withdrawal Scale [CWS]) (UK based participants only)
To assess evidence of absorption of GWP42004. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female participants aged 18 years or above
• Clinically diagnosed with Type 2 diabetes
• Participants receiving oral metformin (≥ 1000 mg per day) as anti-diabetic treatment who have received a stable dose for at least three months prior to screening (Visit 1) and willing to maintain a stable dose for the duration of the trial
• HbA1c level of >7% - ≤9 % (53 - 74.9 mmol/mol)
• BMI of>25 - <40 (>23 - <40 for Asian populations)
• No changes in diet or exercise for three months prior to study entry and participant agrees to keep stable for the duration of the study
• Capable of complying with the study requirements and completing the study (in the opinion of the investigator)
• Willing and able to give written informed consent
• Willing and able to comply with all study requirements
• 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 |
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E.4 | Principal exclusion criteria |
• Participant is taking or has taken insulin at any point in the year prior to screening (does not include short term use (<10 days) to treat acute events)
• Participant is taking or has taken anti-diabetic treatment (other than metformin) at any point in the three months prior to screening
• Any concomitant medications which, in the opinion of the investigator, could affect the primary endpoint should remain stable or not be prescribed in the one month prior to Visit 1 or during the study period.
• Any known or suspected history of:
o alcohol or substance abuse
o epilepsy or recurrent seizures
• Participants receiving treatment with antidepressants or under observation for depression.
• BDI-II item 9 score of 1, 2 or 3
• Participant who has significant history of suicidal ideation or self-harm.
• Recent blood loss (including blood donation) within three months of screening
• Haemolytic anaemia
• Genetic abnormality in haemoglobin molecule (e.g. sickle cell anaemia)
• Clinically significant cardiac, renal or hepatic impairment in the opinion of the investigator
• Any known or suspected hypersensitivity to cannabinoids (CBs) or any of the excipients of the Investigational Medicinal Products (IMPs)
• Has significantly impaired renal function as evidenced by a creatinine clearance lower than 40mL/min at Visit 1
• Has significantly impaired hepatic function at Visit I (alanine aminotransferase [ALT] levels >5X upper limit of normal [ULN] or total bilirubin [TBL] levels> 2X ULN). If the ALT or aspartate aminotransferase levels are >3X ULN and the TBL levels >2X ULN (or International Normalised Ratio > 1.5), then this participant should not enter the study
• Female participants of child bearing potential and male participants whose partner is of child bearing potential, unless willing to ensure that they or their partner use effective double barrier contraception
• Female participant who is pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter
• Participants who have received an IMP within the 12 weeks prior to the screening visit
• 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, may influence the result of the study, or the participant's ability to participate in the study
• Following a physical examination, the participant has 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 who have previously undergone bariatric surgery
• Travel outside the country of residence planned during the study, unless the participant has prior permission from the embassy of the destination country
• Participants previously randomised into this study
• The patient is currently using or has used cannabis or cannabinoid based medications within 30 days of study entry and is unwilling to abstain for the duration of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the efficacy of 2, 5 and 15 mg twice daily of GWP42004 compared with placebo by assessing the change from baseline in glycosylated haemoglobin A 1c (HbA1c). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assessed at: Visit 1 (Day -7); Visit 2 (Day 1); Visit 3 (Day 29), Visit 4 (Day 57) and Visit 5 (Day 85) |
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E.5.2 | Secondary end point(s) |
To evaluate the efficacy of 2, 5 and 15 mg of GWP42004 twice daily compared with placebo on:
• Glycaemic Control:
o Fasting plasma glucose levels
o Glucose response to an Oral Glucose Tolerance Test (OGTT)
o Serum fructosamine levels
o Number of participants with HbA1c levels <7% (53 mmol/mol) following treatment
Insulin related parameters:
o Fasting plasma insulin levels
o Insulin resistance (by Homeostatic Model Assessment 2 for Insulin Resistance)
o Insulin response to OGTT
o Pro-insulin
o C-peptide
o Beta cell function (by Homeostatic Model Assessment 2 for beta cell protection)
• BMI
• Lipid parameters:
o Total cholesterol levels
o High Density Lipoprotein-cholesterol levels
o Serum triglyceride levels
• A marker of inflammation:
o High sensitivity C-Reactive Protein levels
• Cardiovascular parameters:
o Blood pressure
• Health economics:
o Diabetes Treatment Satisfaction Questionnaire (status version) (DTSQs)
o Overall health Visual Analogue Scale (VAS)
To assess the safety and tolerability of GWP42004 compared with placebo on:
• AEs
• Vital signs
• BDI-II
• C-SSRS
• ECG
• Laboratory findings
• Physical examination
• Blood glucose safety (SMBG)
o Rates of hypoglycaemia
• CWS (UK-based participants only)
Evidence of absorption of GWP42004:
• Pre- and post-dose plasma levels of GWP42004 and metabolites |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy
Fasting plasma glucose - V2, 3, 4 & 5
Glucose response to OGTT - V2 & 5
Serum fructosamine - V2 & 5
Participants with HbA1c <7% - V3, 4 & 5
Fasting plasma insulin - V2, 3, 4 & 5
Insulin resistance - V2, 3, 4 & 5
Insulin response to OGTT - V2 & 5
Pro-insulin - V2 & 5
C-peptide - V2 & 5
B-cell function - V2, 3, 4 & 5
BMI - V2, 3, 4 & 5
Total cholesterol - V2 & 5
HDL-cholesterol - V2 & 5
Serum triglyceride - V2 & 5
CRP- V2 & 5
Blood pressure - V2, 3, 4 & 5
DTSQ - V2, 3, 4 & 5
Health VAS - V2, 3, 4 & 5
Safety- V1, 2, 3, 4 & 5 except where indicated
A Es
Vital signs
BDI-II
C-SSRS - V2, 3, 4 & 5
ECG - V1 & 5
Labs
Physical exam
Rates of hypoglycaemia
CWS (UK) - V2, 2 days before V5 & 1, 3 and
7 days after V5
Absorption
Plasma GWP42004 & metabolites - V2 & 5 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |