A Randomised, Double Blind, Placebo Controlled, Parallel Group, Dose Ranging Study of GWP42004 as Add on to Metformin in the Treatment of Participants With Type 2 Diabetes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 207
- 试验地点
- 25
- 主要终点
- Change from baseline to the end of treatment in mean glycosylated haemoglobin A1c (HbA1c) level.
研究概览
简要总结
A study to compare the change in glycaemic control in participants with Type 2 diabetes when treated with GWP42004 or placebo as add-on therapy to metformin over a period of 12 weeks. The safety and tolerability of GWP42004 compared with placebo will also be assessed.
详细描述
This 14 week (one week baseline, 12 week treatment period and one week follow-up), multicentre, randomised, double blind, placebo controlled, parallel group study will evaluate the efficacy, safety and tolerability of 2, 5 and 15 mg of GWP42004 as add on to metformin compared with placebo in participants with Type 2 diabetes.
Eligible participants will enter the study at a screening visit (Visit 1, Day -7) where the following information will be obtained for each participant:
- Informed consent
- Demographics
- Medical history
- Concomitant medications
- Electrocardiogram (ECG)
- Physical examination
- Vital signs
- Body weight
- Height
- Body Mass Index (BMI)
- Beck Depression Inventory-II (BDI-II)
- Safety blood test (biochemistry and haematology)
- Efficacy blood test (HbA1c)
- Urinalysis (including drugs of abuse screen)
- Pregnancy test (if appropriate)
Once all inclusion and exclusion criteria have been reviewed, participants will be commence a seven day baseline period. The day before Visit 2, participants will perform blood glucose tests and record the results, along with the associated time of assessment, in the study diary. Participants will then fast overnight.
Participants will return to the clinic at Visit 2 (Day 1) and following review of all inclusion and exclusion criteria, the following information will be obtained for each participant:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant is willing and able to give informed consent for participation in the study (see Section 15.2).
- •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 enrolment (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).
- •Participant is able (in the investigators opinion) and willing to comply with all study requirements.
- •Participant is willing for his or her name to be notified to the responsible authorities for participation in this study, as applicable in individual countries.
- •Participant is willing to allow his or her primary care practitioner and consultant, if appropriate, to be notified of participation in the study.
排除标准
- •Participant is taking or has taken insulin at any point in the last year (does not include short term use (<10 days) to treat acute events).
- •Participant is taking or has taken anti-diabetic treatment (other than metformin) 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 of suspected history of:
- •Alcohol or substance abuse.
- •Epilepsy or recurrent seizures.
- •Participants receiving treatment with antidepressants or under observation for depression.
- •BDI-II item 9 score of 1, 2 or
- •Participant who has significant history of suicidal ideation or self-harm.
- •Recent (within three months of screening) blood loss (including blood donation).
- •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.
- •Has significantly impaired renal function as evidenced by a creatinine clearance lower than 40 mL/min at Visit
- •Has significantly impaired hepatic function at Visit 1 (alanine aminotransferase (ALT) levels >5x upper limit of normal (ULN) or total bilirubin (TBL) levels > 2x ULN). If the ALT or aspartate aminotransferase (AST) levels are >3x ULN and the TBL levels >2x ULN (or International Normalised Ratio (INR) >1.5), then this participant should not enter the study.
- •Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMPs.
- •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 Investigational Medicinal Product (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.
研究组 & 干预措施
15 mg GWP42004 bid
Licaps® size double zero (Size 00) hard gelatin capsules containing 15 mg GWP42004 dissolved in excipients Macrogolglycerol Ricinoleate and Oleoyl macrogol-6-glycerides. One capsule taken twice daily for 12 weeks.
干预措施: GWP42004 (Drug)
2 mg GWP42004 bid
Licaps® size double zero (Size 00) hard gelatin capsules containing 2 mg GWP42004 dissolved in excipients Macrogolglycerol Ricinoleate and Oleoyl macrogol-6-glycerides. One capsule taken twice daily for 12 weeks.
干预措施: GWP42004 (Drug)
5 mg GWP42004 bid
Licaps® size double zero (Size 00) hard gelatin capsules containing 5 mg GWP42004 dissolved in excipients Macrogolglycerol Ricinoleate and Oleoyl macrogol-6-glycerides. One capsule taken twice daily for 12 weeks.
干预措施: GWP42004 (Drug)
Placebo
Licaps® size double zero (Size 00) hard gelatin capsules containing excipients Macrogolglycerol Ricinoleate and Oleoyl macrogol-6-glycerides. One capsule taken twice daily for 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change from baseline to the end of treatment in mean glycosylated haemoglobin A1c (HbA1c) level.
时间窗: Baseline (Day 1) and End of treatment (Day 85)
At baseline and at the end of treatment, a fasting blood sample is taken for measurement of HbA1c levels. Values are calculated as a percentage of total haemoglobin. A decrease from baseline to the end of treatment in base per cent values, a negative value, indicates an improvement.
次要结局
- Change from baseline to the end of treatment in mean serum glucose concentration two hours post glucose challenge (Oral Glucose Tolerance Test [OGTT])(Baseline (Day 1) and End of treatment (Day 85))
- Change from baseline to the end of treatment in mean C-peptide concentration.(Baseline (Day 1) and End of treatment (Day 85))
- Change from baseline to the end of treatment in mean beta cell function measured by Homeostasis Model Assessment 2 (HOMA2-%B).(Baseline (Day 1) and End of treatment (Day 85))
- Change from baseline to the end of treatment in mean serum total cholesterol concentration.(Baseline (Day 1) and End of treatment (Day 85))
- Change from baseline to the end of treatment in mean serum High Density Lipoprotein (HDL)-cholesterol concentration.(Baseline (Day 1) and End of treatment (Day 85))
- Change from baseline to the end of treatment in mean Diabetes Treatment Satisfaction Questionnaire (DTSQ): Overall Treatment Satisfaction total score.(Baseline (Day 1) and End of treatment (Day 85))
- Change from baseline to the end of treatment in mean fasting plasma glucose concentration.(Baseline (Day 1) and End of treatment (Day 85))
- Change from baseline to the end of treatment in mean serum fructosamine concentration.(Baseline (Day 1) and End of treatment (Day 85))
- Change from baseline to the end of treatment in the number of participants with a HbA1c level below 7%.(Baseline (Day 1) and End of treatment (Day 85))
- Change from baseline to the end of treatment in mean fasting plasma insulin concentration.(Baseline (Day 1) and End of treatment (Day 85))
- Change from baseline to the end of treatment in mean serum insulin concentration two hours post glucose challenge (Oral Glucose Tolerance Test [OGTT])(Baseline (Day 1) and End of treatment (Day 85))
- Change from baseline to the end of treatment in mean C-reactive protein (CRP) concentration.(Baseline (Day 1) and End of treatment (Day 85))
- Change from baseline to the end of treatment in mean blood pressure.(Baseline (Day 1) and End of treatment (Day 85))
- Change from baseline to the end of treatment in mean insulin resistance measured by Homeostasis Model Assessment 2 (HOMA2-IR).(Baseline (Day 1) and End of treatment (Day 85))
- Change from baseline to the end of treatment in mean pro-insulin concentration.(Baseline (Day 1) and End of treatment (Day 85))
- Change from baseline to the end of treatment in mean Body Mass Index (BMI).(Baseline (Day 1) and End of treatment (Day 85))
- Change from baseline to the end of treatment in mean overall health Visual Analogue Scale (0-100) total score.(Baseline (Day 1) and End of treatment (Day 85))
- The number of participants with a treatment-emergent flag using the Columbia-Suicide Severity Rating Scale (C-SSRS) during the course of the study.(Baseline (Day 1) to End of treatment (Day 85))
- Incidence of adverse events (AEs) as a measure of patient safety.(Screening (Day -7) to Final follow-up (Day 92))
- Change from baseline to the end of treatment in mean Beck Depression Inventory-II (BDI-II) total score.(Baseline (Day 1) and End of treatment (Day 85))
- Incidence of hypoglycaemic episodes during the course of the study.(Screening (Day -7) to End of treatment (Day 85))
- Change from baseline to the end of treatment in mean serum triglyceride concentration.(Baseline (Day 1) and End of treatment (Day 85))
- Change from baseline to the end of treatment in mean Diabetes Treatment Satisfaction Questionnaire (DTSQ): Glycaemic Control total score.(Baseline (Day 1) and End of treatment (Day 85))
- Change from baseline to the end of study in mean Cannabis Withdrawal Scale (CWS) total score.(Baseline (Day 1) and Final follow-up (Day 92))