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A Study of GWP42004 as Add on to Metformin in the Treatment of Participants With Type 2 Diabetes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02053272
Recruitment Status : Completed
First Posted : February 3, 2014
Last Update Posted : September 5, 2016
Sponsor:
Information provided by (Responsible Party):
GW Research Ltd

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Drug: GWP42004 Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 207 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : February 2014
Actual Primary Completion Date : February 2016
Actual Study Completion Date : February 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: 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.
Drug: GWP42004
The total dose administered within any 24-hour interval will be two capsules (typically 12 hours apart).
Other Name: Delta-9-tetrahydrocannabivarin

Active Comparator: 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.
Drug: GWP42004
The total dose administered within any 24-hour interval will be two capsules (typically 12 hours apart).
Other Name: Delta-9-tetrahydrocannabivarin

Active Comparator: 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.
Drug: GWP42004
The total dose administered within any 24-hour interval will be two capsules (typically 12 hours apart).
Other Name: Delta-9-tetrahydrocannabivarin

Placebo Comparator: 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.
Drug: Placebo
The total dose administered within any 24-hour interval will be two capsules (typically 12 hours apart).
Other Name: Placebo control




Primary Outcome Measures :
  1. Change from baseline to the end of treatment in mean glycosylated haemoglobin A1c (HbA1c) level. [ Time Frame: 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.


Secondary Outcome Measures :
  1. Change from baseline to the end of treatment in mean fasting plasma glucose concentration. [ Time Frame: 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 fasting plasma glucose concentrations. A decrease from baseline to the end of treatment, a negative value, indicates an improvement.

  2. Change from baseline to the end of treatment in mean serum glucose concentration two hours post glucose challenge (Oral Glucose Tolerance Test [OGTT]) [ Time Frame: Baseline (Day 1) and End of treatment (Day 85) ]
    Fasting blood samples are taken at 0 minutes prior to a glucose drink and at 30 and 120 minutes post drink. The OGTT measures the serum glucose levels at two hours (120 minutes) compared to 0 minutes. The extent of the elevation in serum glucose levels following a glucose drink are compared between baseline and the end of treatment. A reduction in the elevation of serum glucose levels at the end of treatment, a negative value, indicates an improvement.

  3. Change from baseline to the end of treatment in mean serum fructosamine concentration. [ Time Frame: 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 serum fructosamine concentrations. A decrease from baseline to the end of treatment, a negative value, indicates an improvement.

  4. Change from baseline to the end of treatment in the number of participants with a HbA1c level below 7%. [ Time Frame: 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 glycosylated haemoglobin A1c levels. Values are calculated as a percentage of total haemoglobin. An increase in the number of participants with HbA1c levels below 7% from baseline to the end of treatment, a positive value, indicates an improvement.

  5. Change from baseline to the end of treatment in mean fasting plasma insulin concentration. [ Time Frame: 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 fasting plasma insulin concentrations. An increase from baseline to the end of treatment, a positive value, indicates an improvement.

  6. Change from baseline to the end of treatment in mean insulin resistance measured by Homeostasis Model Assessment 2 (HOMA2-IR). [ Time Frame: 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 insulin resistance calculated by HOMA2-IR. HOMA2-IR is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin resistance, which is the reciprocal of insulin sensitivity (%S) (100/%S) as a percentage of a normal reference population (normal young adults). A decrease from baseline to the end of treatment, a negative value, indicates an improvement.

  7. Change from baseline to the end of treatment in mean serum insulin concentration two hours post glucose challenge (Oral Glucose Tolerance Test [OGTT]) [ Time Frame: Baseline (Day 1) and End of treatment (Day 85) ]
    Fasting blood samples are taken at 0 minutes prior to a glucose drink and at 30 and 120 minutes post drink. The OGTT measures the serum insulin levels at two hours (120 minutes) compared to 0 minutes. The extent of the elevation in serum insulin levels following a glucose drink are compared between baseline and the end of treatment. An increase in the elevation of serum insulin levels from baseline to the end of treatment, a positive value, indicates an improvement.

  8. Change from baseline to the end of treatment in mean pro-insulin concentration. [ Time Frame: 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 pro-insulin concentrations. A decrease from baseline to the end of treatment, a negative value, indicates an improvement.

  9. Change from baseline to the end of treatment in mean C-peptide concentration. [ Time Frame: 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 C-peptide concentrations. An increase from baseline to the end of treatment, a positive value, indicates an improvement.

  10. Change from baseline to the end of treatment in mean beta cell function measured by Homeostasis Model Assessment 2 (HOMA2-%B). [ Time Frame: 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 beta cell function calculated by HOMA2. HOMA2 is a computer model that uses fasting plasma insulin and glucose concentrations to estimate beta cell function (%B) as a percentage of a normal reference population (normal young adults). An increase from baseline to the end of treatment, a positive value, indicates an improvement.

  11. Change from baseline to the end of treatment in mean Body Mass Index (BMI). [ Time Frame: Baseline (Day 1) and End of treatment (Day 85) ]
    Body Mass Index (kg/m^2) is calculated at baseline and the end of treatment. A decrease from baseline to the end of treatment, a negative value, indicates an improvement.

  12. Change from baseline to the end of treatment in mean serum total cholesterol concentration. [ Time Frame: 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 serum total cholesterol concentrations. A decrease from baseline to the end of treatment, a negative value, indicates an improvement.

  13. Change from baseline to the end of treatment in mean serum High Density Lipoprotein (HDL)-cholesterol concentration. [ Time Frame: 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 serum HDL-cholesterol. An increase from baseline to the end of treatment, a positive value, indicates an improvement.

  14. Change from baseline to the end of treatment in mean serum triglyceride concentration. [ Time Frame: 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 serum triglyceride concentrations. A decrease from baseline to the end of treatment, a negative value, indicates an improvement.

  15. Change from baseline to the end of treatment in mean C-reactive protein (CRP) concentration. [ Time Frame: Baseline (Day 1) and End of treatment (Day 85) ]
    At baseline and at the end of treatment, a fasting blood sample is taken for high sensitivity measurement of CRP concentrations. A decrease from baseline to the end of treatment, a negative value, indicates an improvement.

  16. Change from baseline to the end of treatment in mean blood pressure. [ Time Frame: Baseline (Day 1) and End of treatment (Day 85) ]
    Blood pressure is measured at baseline and at the end of treatment. A decrease from baseline to the end of treatment, a negative value, indicates an improvement.

  17. Change from baseline to the end of treatment in mean Diabetes Treatment Satisfaction Questionnaire (DTSQ): Overall Treatment Satisfaction total score. [ Time Frame: Baseline (Day 1) and End of treatment (Day 85) ]
    The DTSQ (status version) is a self-administered questionnaire consisting of eight items. Six of the eight items are rated from 0 (very dissatisfied, inconvenient, inflexible, etc.) to 6 (very satisfied, convenient, flexible, etc.) and are summed to produce an Overall Treatment Satisfaction score. As such, an increase from baseline to the end of treatment, a positive value, indicates an improvement.

  18. Change from baseline to the end of treatment in mean Diabetes Treatment Satisfaction Questionnaire (DTSQ): Glycaemic Control total score. [ Time Frame: Baseline (Day 1) and End of treatment (Day 85) ]
    The DTSQ (status version) is a self-administered questionnaire consisting of eight items. Two of the eight items are used to assess 'perceived frequency of hyperglycaemia' and 'perceived frequency of hypoglycaemia', both of which are rated from 0 (none of the time) to 6 (most of the time) and are summed to produce a Glycaemic Control score. As such, a decrease from baseline to the end of treatment, a negative value, indicates an improvement.

  19. Change from baseline to the end of treatment in mean overall health Visual Analogue Scale (0-100) total score. [ Time Frame: Baseline (Day 1) and End of treatment (Day 85) ]
    Participants are asked to assess their overall health status using a health Visual Analogue Scale (0-100), where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine'. An increase from baseline to the end of treatment, a positive value, indicates an improvement.

  20. Incidence of adverse events (AEs) as a measure of patient safety. [ Time Frame: Screening (Day -7) to Final follow-up (Day 92) ]
    The incidence of treatment-emergent AEs is recorded for the study duration, and the number of participants who experienced an adverse event is presented.

  21. Change from baseline to the end of treatment in mean Beck Depression Inventory-II (BDI-II) total score. [ Time Frame: Baseline (Day 1) and End of treatment (Day 85) ]
    The BDI-II is a multiple choice self-reported inventory that is one of the most widely used instruments for measuring the severity of depression. There are 21 questions or items, each having four possible responses. Each response is assigned a score ranging from zero to three, indicating the severity of the symptom. Items 1 to 13 assess symptoms that are psychological in nature, while items 14 to 21 assess symptoms that are more physical. The sum of all BDI-II item scores indicates the severity of depression. For participants eligible for this study, a score of 21 or over represents depression. The BDI-II can distinguish between different subtypes of depressive disorders, such as major depression and dysthymia. A decrease from baseline to the end of treatment, a negative value, indicates an improvement.

  22. The number of participants with a treatment-emergent flag using the Columbia-Suicide Severity Rating Scale (C-SSRS) during the course of the study. [ Time Frame: Baseline (Day 1) to End of treatment (Day 85) ]
    Participants are scored at each clinic visit for the following outcomes using the C-SSRS: suicidal ideation, suicidal behaviour, suicidality (including complete suicidality). Possible flags are as follows: "Wish to be Dead", "Non-specific Active Suicidal Thoughts", "Active Suicidal Ideation Without Intent", "Active Suicidal Ideation With Intent, No Plan", "Active Suicidal Ideation With Intent and Plan". The number of participants with a treatment-emergent flag is presented.

  23. Incidence of hypoglycaemic episodes during the course of the study. [ Time Frame: Screening (Day -7) to End of treatment (Day 85) ]
    The incidence of treatment-emergent hypoglycaemic episodes (blood glucose concentration below 3 mmol/L) is recorded for the study duration, and the number of participants who experienced a hypoglycaemic episode is presented.

  24. Change from baseline to the end of study in mean Cannabis Withdrawal Scale (CWS) total score. [ Time Frame: Baseline (Day 1) and Final follow-up (Day 92) ]
    The CWS is validated and used as a diagnostic instrument in clinical and research settings where regular monitoring of withdrawal symptoms is required. The CWS will be completed for UK-based participants only. The CWS is a 19 item scale with each item (withdrawal symptom) measured on a 0-10 point scale (0 = Not at all, 5 = moderately, 10 = Extremely). For each item, the participant is asked to record the extent to which it was experienced in the last 24 hours and also to rate its negative impact on their normal daily activities (i.e., two separate scores are recorded for each item using the same 0-10 scale). Scores are summed over the 19 items for each measure, extent of experience and negative impact on normal daily activities. An increase from baseline to the end of study, a positive value, indicates withdrawal.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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 3.
  • 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 1.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02053272


Locations
Show Show 25 study locations
Sponsors and Collaborators
GW Research Ltd
Investigators
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Principal Investigator: Melanie Davies, MB ChB, MRCP, MD, FRCP Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Road, Leicester LE5 4WP, UK
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Responsible Party: GW Research Ltd
ClinicalTrials.gov Identifier: NCT02053272    
Other Study ID Numbers: GWDM1302
2013-001140-61 ( EudraCT Number )
First Posted: February 3, 2014    Key Record Dates
Last Update Posted: September 5, 2016
Last Verified: September 2016
Keywords provided by GW Research Ltd:
Diabetes
Glycaemic control
Delta-9-tetrahydrocannabivarin
Cannabinoids
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases