Clinical Trials/NCT01217112

NCT01217112

Completed

Phase 2

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

Jazz Pharmaceuticals5 sites in 1 country62 target enrollmentOctober 2010

ConditionsDyslipidemias Diabetes Mellitus, Type 2

InterventionsGWP42004 Placebo GWP42003

DrugsGWP42003 GWP42004 Placebo

Overview

Phase: Phase 2
Intervention: GWP42004
Conditions: Dyslipidemias
Sponsor: Jazz Pharmaceuticals
Enrollment: 62
Locations: 5
Primary Endpoint: The Change From Baseline in Mean Serum High Density Lipoprotein Cholesterol Concentration After 91 Days (13 Weeks) of Treatment
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

October 2010

End Date

September 2012

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Jazz Pharmaceuticals

Responsible Party

Sponsor

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;

Arms & Interventions

GWP42004 and placebo

Contains GWP42004 5 mg and placebo (excipients only)

Intervention: GWP42004

GWP42004 and placebo

Contains GWP42004 5 mg and placebo (excipients only)

Intervention: Placebo

1:1 GWP42003 : GWP42004

Contains 5 mg each of GWP42003 and GWP42004

Intervention: GWP42003

1:1 GWP42003 : GWP42004

Contains 5 mg each of GWP42003 and GWP42004

Intervention: GWP42004

20:1 GWP42003 : GWP42004

Contains 100 mg GWP42003 and 5 mg GWP42004

Intervention: GWP42003

20:1 GWP42003 : GWP42004

Contains 100 mg GWP42003 and 5 mg GWP42004

Intervention: GWP42004

Placebo

Contains excipients only

Intervention: Placebo

GWP42003 and placebo

Contains 100 mg GWP42003 and placebo (excipients only)

Intervention: GWP42003

GWP42003 and placebo

Contains 100 mg GWP42003 and placebo (excipients only)

Intervention: Placebo

Outcomes

Primary Outcomes

The Change From Baseline in Mean Serum High Density Lipoprotein Cholesterol Concentration After 91 Days (13 Weeks) of Treatment

Time Frame: Baseline (Day 1) and End of treatment (Day 92)

At baseline and the end of treatment, an approximately 30 mL fasting blood sample was taken for measurement of serum High Density Lipoprotein cholesterol. An increase from baseline to the end of treatment, a positive value, indicates an improvement.

Secondary Outcomes

The Change From Baseline in Mean Serum Apolipoprotein B Concentration After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Serum Apolipoprotein B : Apolipoprotein A Ratio After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Serum Non-Esterified Fatty Acid Concentration After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Fasting Glucose Concentration After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Fructosamine Concentration After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Glycated Haemoglobin Concentration After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
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])(Baseline (Day 1) and End of treatment (Day 92))
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)(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Fasting Insulin Concentration After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean C-peptide Concentration After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean High Density Lipoprotein Cholesterol Concentration by Ultracentrifugation After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Serum Total Cholesterol Concentration After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Total Cholesterol Concentration by Ultracentrifugation After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Serum Low Density Lipoprotein Cholesterol Concentration After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Low Density Lipoprotein Cholesterol Concentration by Ultracentrifugation After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Serum High Density Lipoprotein : Low Density Lipoprotein Cholesterol Ratio After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean High Density Lipoprotein : Low Density Lipoprotein Cholesterol Ratio by Ultracentrifugation After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Very Low Density Lipoprotein Cholesterol Concentration by Ultracentrifugation After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Serum Triglyceride Concentration After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Triglyceride Concentration by Ultracentrifugation After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Serum Apolipoprotein A Concentration After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Insulin Resistance Measured by Homeostasis Model Assessment 2 (HOMA2-IR) After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Insulin Sensitivity Measured by Homeostasis Model Assessment 2 (HOMA2) After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Insulin B Cell Function Measured by Homeostasis Model Assessment 2 (HOMA2) After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Body Mass Index After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Waist-to-hip Ratio After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Body Weight After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Waist Measurement After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Hip Measurement After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Visceral Abdominal Fat After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Subcutaneous Abdominal Fat After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Total Abdominal Fat After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Internal Non-Abdominal Fat After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Subcutaneous Non-Abdominal Fat After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Total Non-Abdominal Fat After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Total Internal Fat After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Total Subcutaneous Fat After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Total Fat After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Abdominal Adiposity After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean % Liver Fat After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
The Change From Baseline in Mean Appetite 0-10 Numerical Rating Scale Score After 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and End of treatment (Day 92))
Adverse Events as a Measure of Patient Safety(Day 1 - Day 92)
The Change From Baseline in Mean Beck Depression Inventory-II (BDI-II) Score at the End of 91 Days (13 Weeks) of Treatment(Baseline (Day 1) and the End of Treatment (Day 92))