Clinical trial NCT01217112: GWMD1092 - GWP42003 : GWP42004 Together Plus Alone in Type II Diabetes
Official title: A Randomised, Double Blind, Placebo Controlled, Parallel Group, Pilot Study of 1:1 and 20:1 Ratio of Formulated GWP42003 : GWP42004 Plus GWP42003 and GWP42004 Alone in the Treatment of Dyslipidaemia in Subjects With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dyslipidemias
Diabetes Mellitus, Type 2
Keywords: Dyslipidemias
Diabetes
Liver Fat
Body Fat
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2010-10-08
Enrollment: 62
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 15-19 week study is being conducted by GW Pharma Ltd as a pilot study in order to determine the efficacy and safety of two cannabinoids: GWP42004 and GWP42003 alone, or in combination in patients with Type 2 diabetes. This is the first study to determine whether the study medications have a positive benefit for subjects on their cholesterol levels, body weight, liver fat content and other metabolic parameters compared with a placebo medication.

Detailed description: In this study there was a 1-5 week baseline period followed by a 13 week treatment period, and a one week follow-up. Eligible subjects entered the study at a screening visit (Visit 1) before returning for randomisation (Visit 2, Day 1). At the discretion of the investigator (based on individual subjects), Visit 1 could be split into two separate visits (Visits 1A and B) to allow a 21-day washout period of prohibited medications prior to blood sampling for eligibility. Further outpatient study visits (for assessment purposes) took place at the study site at the end of Week 4 of treatment (Visit 3, Day 29), and at the overall end of treatment at Week 13 (Visit 5, Day 92). A telephone assessment was also performed at Day 57 (Visit 4) and at Week 14 (Visit 6, Day 99) for safety follow-up purposes.

During the 13 week randomised treatment phase, subjects received blinded, oral doses of their allocated randomised treatment twice daily. Treatment was self-administered on an outpatient basis, once in the morning and once in the evening for 13 weeks. Subjects were instructed to time study medication to 30 minutes before breakfast and evening meals.

Physical and metabolic parameters were assessed before, during and after treatment to evaluate clinical response. Diabetic and dyslipidaemic medication usage (where applicable), and appetite 0-10 NRS data were collected daily during the treatment period, using the study diary.

Eligibility criteria: Inclusion Criteria:

* Clinically diagnosed with Type 2 diabetes, with residual islet cell function;
* Diet controlled or receiving oral anti-diabetic treatment (metformin or other biguanides and/or sulphonyl ureas) who have received a stable dose for at least 3 months prior to enrollment;
* High Density Lipoprotein cholesterol ≤ 1.3mmol/L (females), ≤ 1.2mmol/L (males);
* Glycosylated haemoglobin levels of ≤ 10%;
* Triglycerides ≤ 10mmol/L;
* Willing to maintain a stable dose of oral anti-diabetic and/or lipid-lowering agents/medications that may have an effect on plasma/serum glucose, insulin or lipid parameters for the duration of the study, where applicable;
* No changes in diet or exercise for four weeks prior to and subject agrees to keep stable for the duration of the study (in the opinion of the investigator);

Exclusion Criteria:

* Subject is taking insulin (i.e. they are insulin-dependent);
* Taking the following categories of medicines: fibrates, Thiazolidinediones, therapeutic Omega-3 fatty acids, alpha-glucosidase inhibitors and unwilling abstain for the duration of the study;
* Currently using or has used recreational cannabis, medicinal cannabis, cannabinoid medications (including Sativex®), or synthetic cannabinoid based medications within 30 days prior to study entry and unwilling to abstain for the duration for the study;
* Any known or suspected history of:

  * alcohol or substance abuse
  * epilepsy or recurrent seizures;
* Any known or suspected history of depression sufficient to require treatment with antidepressants or disrupt ordinary life at the discretion of the investigator);
* Subject who has significant history of anxiety, suicidal ideation or self-harm;
* Clinically significant cardiac, renal or hepatic impairment in the opinion of the investigator;
* Genetic dyslipidaemic condition in the opinion of the investigator;
* Currently taking a lipid lowering agent and a stable dose has not been maintained for at least four weeks randomisation (Visit 2);
* Female subject, who is pregnant, lactating or planning pregnancy during the course of the study and for three months from date of last dose;
* Female subjects of child bearing potential unless willing to use two forms of contraception, one of which must be barrier contraception (e.g. female condom or occlusive cap (diaphragm or cervical vault/caps) with spermicide) during the study and for three months thereafter;
* Male subjects whose partner is 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 (e.g. female condom or occlusive cap (diaphragm or cervical vault/caps) with spermicide) during the study and for three months thereafter;
* Body weight \> 150kg;
* Travel outside the country of residence planned during the study;
* Currently receiving a prohibited medication and unwilling to stop at the screening visit and for the duration of the study;
* Received an unapproved Investigational Medicinal Product (IMP) within the 30 days before the screening visit;
* In the opinion of the investigator, is not considered to be suitable for the study;
* Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP(s);
* Any other significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, may influence the result of the study, or the subject's ability to participate in the study;
* Has a postural drop of ≥ 20 mmHg in systolic blood pressure at Visit 1;
* Any abnormalities identified during the physical exam at Visit 1 that in the opinion of the investigator, would prevent the subject from safe participation in the study;
* Unwilling to abstain from donation of blood during the study.

Primary outcomes:
measure: The Change From Baseline in Mean Serum High Density Lipoprotein Cholesterol Concentration After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
Secondary outcomes:
measure: The Change From Baseline in Mean High Density Lipoprotein Cholesterol Concentration by Ultracentrifugation After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Serum Total Cholesterol Concentration After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Total Cholesterol Concentration by Ultracentrifugation After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Serum Low Density Lipoprotein Cholesterol Concentration After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Low Density Lipoprotein Cholesterol Concentration by Ultracentrifugation After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Serum High Density Lipoprotein : Low Density Lipoprotein Cholesterol Ratio After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean High Density Lipoprotein : Low Density Lipoprotein Cholesterol Ratio by Ultracentrifugation After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Very Low Density Lipoprotein Cholesterol Concentration by Ultracentrifugation After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Serum Triglyceride Concentration After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Triglyceride Concentration by Ultracentrifugation After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Serum Apolipoprotein A Concentration After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Serum Apolipoprotein B Concentration After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Serum Apolipoprotein B : Apolipoprotein A Ratio After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Serum Non-Esterified Fatty Acid Concentration After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Fasting Glucose Concentration After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Fructosamine Concentration After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Glycated Haemoglobin Concentration After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline to the End of 91 Days (13 Weeks) of Treatment in the Mean Serum Glucose Concentration Two Hours Post Glucose Challenge (Oral Glucose Tolerance Test [OGTT])
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline to the End of 91 Days (13 Weeks) of Treatment in the Mean Serum Insulin Concentration Two Hours Post Glucose Challenge (Oral Glucose Tolerance Test)
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Fasting Insulin Concentration After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean C-peptide Concentration After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Insulin Resistance Measured by Homeostasis Model Assessment 2 (HOMA2-IR) After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Insulin Sensitivity Measured by Homeostasis Model Assessment 2 (HOMA2) After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Insulin B Cell Function Measured by Homeostasis Model Assessment 2 (HOMA2) After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Body Mass Index After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Waist-to-hip Ratio After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Body Weight After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Waist Measurement After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Hip Measurement After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Visceral Abdominal Fat After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Subcutaneous Abdominal Fat After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Total Abdominal Fat After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Internal Non-Abdominal Fat After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Subcutaneous Non-Abdominal Fat After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Total Non-Abdominal Fat After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Total Internal Fat After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Total Subcutaneous Fat After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Total Fat After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Abdominal Adiposity After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean % Liver Fat After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: The Change From Baseline in Mean Appetite 0-10 Numerical Rating Scale Score After 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and End of treatment (Day 92)
measure: Adverse Events as a Measure of Patient Safety
timeFrame: Day 1 - Day 92
measure: The Change From Baseline in Mean Beck Depression Inventory-II (BDI-II) Score at the End of 91 Days (13 Weeks) of Treatment
timeFrame: Baseline (Day 1) and the End of Treatment (Day 92)
Other outcomes:
Locations:
city: Bury Saint Edmonds
country: United Kingdom
facility: Woolpit Health Centre
city: Bury Saint Edmonds
country: United Kingdom
facility: Mount Farm Surgery
city: Derby
country: United Kingdom
facility: University of Nottingham, Medical School at Derby, Royal Derby Hospital
city: Gorleston-on-Sea, Norfolk
country: United Kingdom
facility: James Paget University Hospital
city: Manchester
country: United Kingdom
facility: MAC UK Neuroscience Ltd.
Study officials:
References:
citation: Jadoon KA, Ratcliffe SH, Barrett DA, Thomas EL, Stott C, Bell JD, O'Sullivan SE, Tan GD. Efficacy and Safety of Cannabidiol and Tetrahydrocannabivarin on Glycemic and Lipid Parameters in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study. Diabetes Care. 2016 Oct;39(10):1777-86. doi: 10.2337/dc16-0650. Epub 2016 Aug 29.