Diabetes Mellitus, Type 2Phase 2NCT02053272
A Study of GWP42004 as Add on to Metformin in the Treatment of Participants With Type 2 Diabetes
A Phase 2 study testing GWP42004 in people with Diabetes Mellitus, Type 2, run by Jazz Pharmaceuticals at 25 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- GWP42004
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 207 participants
- Where
- 25 sitesin 2 countries
- Study dates
- Feb 2014to Feb 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
25 sites in 2 countries.
25 sites in 2 countries
Romania14 sites
Diabol SRL
Brasov, 500365
Nicodiab SRL
Bucharest, 010507
Spitalul Universitar de Urgenta Militar Central "Dr. Carol Davila"
Bucharest, 010825
Institutul National de Diabet
Bucharest, 020475
Centrul Medical 'Sanatatea Ta' SRL
Bucharest, 020614
ArtMedical Clinic
Bucharest, 021107
Societatea Civila Medicala dr. Paveliu
Bucharest, 050538
Consultmed SRL
Iași, 700547
Cabinet Medical Individual Diabet Nutritie si Boli Metabolice
Maramures, 430123
Grandmed SRL
Oradea, 410159
Spitalul Judetean de Urgente Satu Mare
Satu Mare, 440055
Spitalul Clinic Judetean de Urgenta Sibiu
Sibiu, 550245
Gagiu D. Remus Cabinet Medical Individual
Targoviste, 130083
Mediab SRL Diabet Zaharat
Târgu Mureş, 540142
United Kingdom11 sites
St Chad's Surgery
Bath, BA3 2UH
Avondale Surgery
Chesterfield, Derbyshire, S40 4TF
Hathaway Surgery
Chippenham, Wiltshire, SN14 6GT
Hull and East Yorkshire Hospitals NHS Trust
Hull, East Yorkshire, HU3 2JZ
University Hospitals of Leicester NHS Trust
Leicester, Leicestershire, LE5 4QF
Aintree University Hospitals NHS Foundation Trust
Liverpool, Merseyside, L9 7AL
Barts and The London NHS Trust
London, E1 1BB
Churchill Hospital
Oxford, Oxfordshire, OX3 9DU
Salford Royal NHS Foundation Trust
Salford, Greater Manchester, M6 8HD
Avenue Surgery
Warminster, Wiltshire, BA12 9AA
Strensall Medical Practice
York, North Yorkshire, YO32 5UA
About this study
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
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.
Read the detailed description
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:
- Body weight
- BMI
- Physical examination
- Vital signs
- Safety blood test (biochemistry and haematology)
- GWP42004 exposure blood test (plasma levels)
- Efficacy blood test (HbA1c, fasting plasma glucose, serum fructosamine, fasting plasma insulin, HOMA2-IR, pro-insulin, C-peptide, HOMA2-%B, total cholesterol, HDL-cholesterol, serum triglycerides, C-reactive protein)
- Urinalysis
- Concomitant medications
- Adverse events (AEs)
- BDI-II
- Columbia-Suicide Severity Rating Scale (C-SSRS)
- Diabetes Treatment Satisfaction Questionnaire (DTSQs)
- Overall health Visual Analogue Scale (VAS)
- Cannabis withdrawal scale assessment (UK only).
Participants will then be randomised to receive either GWP42004 (2, 5 or 15 mg bid) or placebo to be taken adjunctive to their currently prescribed medication. The first dose will be administered and a Oral Glucose Tolerance Test (OGTT) performed.
A third (Visit 3, Day 29) and fourth (Visit 4, Day 57) visit will take place mid-treatment. The day before these visits, 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. The following information will be obtained for each participant at Visits 3 and 4:
- Body weight
- BMI
- Physical examination
- Vital signs
- Safety blood test (biochemistry and haematology)
- Efficacy blood test (HbA1c, fasting plasma glucose, fasting plasma insulin, HOMA2-IR, HOMA2-%B)
- Urinalysis
- Concomitant medications
- AEs
- BDI-II
- C-SSRS
- DTSQs
- Overall health VAS
A cannabis withdrawal scale assessment will be made by telephone (UK only) between Visits 4 and 5.
A further visit will take place at the end of treatment (Visit 5, Day 85). Two days before this visit, a cannabis withdrawal scale assessment will be made by telephone (UK only). The day before Visit 5, 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. The following information will be obtained for each participant at Visit 5:
the following information will be obtained for each participant:
- Body weight
- BMI
- Physical examination
- ECG
- Vital signs
- Safety blood test (biochemistry and haematology)
- GWP42004 exposure blood test (plasma levels)
- Efficacy blood test (HbA1c, fasting plasma glucose, serum fructosamine, fasting plasma insulin, HOMA2-IR, pro-insulin, C-peptide, HOMA2-%B, total cholesterol, HDL-cholesterol, serum triglycerides, C-reactive protein)
- Urinalysis (including drugs of abuse screen)
- Pregnancy test (if appropriate)
- Concomitant medications
- Adverse events (AEs)
- BDI-II
- OGTT
- C-SSRS
- DTSQs
- Overall health VAS
One, three and seven days following Visit 5 (Days 86, 89 and 92, respectively), further cannabis withdrawal scale assessments will be made by telephone (UK only). A final review of AEs and concomitant medications will be made by telephone to all participants on Day 92.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- GWP42004, Placebo
- Keywords
- Diabetes, Glycaemic control, Delta-9-tetrahydrocannabivarin, Cannabinoids
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GWP42004Drug
Also called Delta-9-tetrahydrocannabivarin
The total dose administered within any 24-hour interval will be two capsules (typically 12 hours apart).
PlaceboDrug
Also called Placebo control
The total dose administered within any 24-hour interval will be two capsules (typically 12 hours apart).
| Study group | Role | What they receive |
|---|---|---|
| 2 mg GWP42004 bid | Active comparator | 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. Receives: Drug: GWP42004 |
| 5 mg GWP42004 bid | Active comparator | 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. Receives: Drug: GWP42004 |
| 15 mg GWP42004 bid | Active comparator | 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. Receives: Drug: GWP42004 |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline to the end of treatment in mean glycosylated haemoglobin A1c (HbA1c) level.
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.
Measured: Baseline (Day 1) and End of treatment (Day 85)
Secondary outcomes (24)
Change from baseline to the end of treatment in mean fasting plasma glucose concentration.
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.
Measured: Baseline (Day 1) and End of treatment (Day 85)
Change from baseline to the end of treatment in mean serum glucose concentration two hours post glucose challenge (Oral Glucose Tolerance Test [OGTT])
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.
Measured: Baseline (Day 1) and End of treatment (Day 85)
Change from baseline to the end of treatment in mean serum fructosamine concentration.
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.
Measured: 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%.
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.
Measured: Baseline (Day 1) and End of treatment (Day 85)
Change from baseline to the end of treatment in mean fasting plasma insulin concentration.
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.
Measured: 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).
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.
Measured: 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])
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.
Measured: Baseline (Day 1) and End of treatment (Day 85)
Change from baseline to the end of treatment in mean pro-insulin concentration.
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.
Measured: Baseline (Day 1) and End of treatment (Day 85)
Change from baseline to the end of treatment in mean C-peptide concentration.
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.
Measured: 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).
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.
Measured: Baseline (Day 1) and End of treatment (Day 85)
Change from baseline to the end of treatment in mean Body Mass Index (BMI).
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.
Measured: Baseline (Day 1) and End of treatment (Day 85)
Change from baseline to the end of treatment in mean serum total cholesterol concentration.
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.
Measured: 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.
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.
Measured: Baseline (Day 1) and End of treatment (Day 85)
Change from baseline to the end of treatment in mean serum triglyceride concentration.
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.
Measured: Baseline (Day 1) and End of treatment (Day 85)
Change from baseline to the end of treatment in mean C-reactive protein (CRP) concentration.
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.
Measured: Baseline (Day 1) and End of treatment (Day 85)
Change from baseline to the end of treatment in mean blood pressure.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: Baseline (Day 1) and End of treatment (Day 85)
Incidence of adverse events (AEs) as a measure of patient safety.
The incidence of treatment-emergent AEs is recorded for the study duration, and the number of participants who experienced an adverse event is presented.
Measured: 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.
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.
Measured: 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.
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.
Measured: Baseline (Day 1) to End of treatment (Day 85)
Incidence of hypoglycaemic episodes during the course of the study.
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.
Measured: Screening (Day -7) to End of treatment (Day 85)
Change from baseline to the end of study in mean Cannabis Withdrawal Scale (CWS) total score.
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.
Measured: Baseline (Day 1) and Final follow-up (Day 92)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2014 (estimated)
- Study startFeb 2014
- Primary completionFeb 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by Jazz PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 207 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jazz Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02053272
- Sponsor's protocol ID
- GWDM1302
- Other IDs
- 2013-001140-61
- Status last verified
- Dec 2022
- First submitted
- 31 Jan 2014
- Last updated
- 20 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02053272
- Acronym / sponsor ID
- GWDM1302
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- Diabetes, Glycaemic control, Delta-9-tetrahydrocannabivarin, Cannabinoids
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 207 participants (actual)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Feb 2014
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 3 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- Body weight
- BMI
- Physical examination
- Vital signs
- Safety blood test (biochemistry and haematology)
- GWP42004 exposure blood test (plasma levels)
- Efficacy blood test (HbA1c, fasting plasma glucose, serum fructosamine, fasting plasma insulin, HOMA2-IR, pro-insulin, C-peptide, HOMA2-%B, total cholesterol, HDL-cholesterol, serum triglycerides, C-reactive protein)
- Urinalysis
- Concomitant medications
- Adverse events (AEs)
- BDI-II
- Columbia-Suicide Severity Rating Scale (C-SSRS)
- Diabetes Treatment Satisfaction Questionnaire (DTSQs)
- Overall health Visual Analogue Scale (VAS)
- Cannabis withdrawal scale assessment (UK only).
Participants will then be randomised to receive either GWP42004 (2, 5 or 15 mg bid) or placebo to be taken adjunctive to their currently prescribed medication. The first dose will be administered and a Oral Glucose Tolerance Test (OGTT) performed.
A third (Visit 3, Day 29) and fourth (Visit 4, Day 57) visit will take place mid-treatment. The day before these visits, 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. The following information will be obtained for each participant at Visits 3 and 4:
- Body weight
- BMI
- Physical examination
- Vital signs
- Safety blood test (biochemistry and haematology)
- Efficacy blood test (HbA1c, fasting plasma glucose, fasting plasma insulin, HOMA2-IR, HOMA2-%B)
- Urinalysis
- Concomitant medications
- AEs
- BDI-II
- C-SSRS
- DTSQs
- Overall health VAS
A cannabis withdrawal scale assessment will be made by telephone (UK only) between Visits 4 and 5.
A further visit will take place at the end of treatment (Visit 5, Day 85). Two days before this visit, a cannabis withdrawal scale assessment will be made by telephone (UK only). The day before Visit 5, 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. The following information will be obtained for each participant at Visit 5:
the following information will be obtained for each participant:
- Body weight
- BMI
- Physical examination
- ECG
- Vital signs
- Safety blood test (biochemistry and haematology)
- GWP42004 exposure blood test (plasma levels)
- Efficacy blood test (HbA1c, fasting plasma glucose, serum fructosamine, fasting plasma insulin, HOMA2-IR, pro-insulin, C-peptide, HOMA2-%B, total cholesterol, HDL-cholesterol, serum triglycerides, C-reactive protein)
- Urinalysis (including drugs of abuse screen)
- Pregnancy test (if appropriate)
- Concomitant medications
- Adverse events (AEs)
- BDI-II
- OGTT
- C-SSRS
- DTSQs
- Overall health VAS
One, three and seven days following Visit 5 (Days 86, 89 and 92, respectively), further cannabis withdrawal scale assessments will be made by telephone (UK only). A final review of AEs and concomitant medications will be made by telephone to all participants on Day 92.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 2 mg GWP42004 bid | Active comparator | Drug: GWP42004Licaps® 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. |
| 5 mg GWP42004 bid | Active comparator | Drug: GWP42004Licaps® 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. |
| 15 mg GWP42004 bid | Active comparator | Drug: GWP42004Licaps® 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. |
| Placebo | Placebo comparator | Drug: PlaceboLicaps® 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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).
Key exclusion criteria (26 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GWP42004Also: Delta-9-tetrahydrocannabivarinThe total dose administered within any 24-hour interval will be two capsules (typically 12 hours apart). | Drug | 15 mg GWP42004 bid, 2 mg GWP42004 bid, 5 mg GWP42004 bid |
| PlaceboAlso: Placebo controlThe total dose administered within any 24-hour interval will be two capsules (typically 12 hours apart). | Drug | Placebo |
Primary outcome
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.
24 secondary outcomes
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)
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)
Change from baseline to the end of treatment in mean serum fructosamine concentration.
Time frame: 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%.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
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)
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)
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)
Change from baseline to the end of treatment in mean pro-insulin concentration.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
Change from baseline to the end of treatment in mean C-peptide concentration.
Time frame: 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).
Time frame: Baseline (Day 1) and End of treatment (Day 85)
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)
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)
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)
Change from baseline to the end of treatment in mean serum triglyceride concentration.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
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)
Change from baseline to the end of treatment in mean blood pressure.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
Incidence of adverse events (AEs) as a measure of patient safety.
Time frame: 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.
Time frame: 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.
Time frame: Baseline (Day 1) to End of treatment (Day 85)
Incidence of hypoglycaemic episodes during the course of the study.
Time frame: Screening (Day -7) to End of treatment (Day 85)
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
25 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GWP42004 in people with Diabetes Mellitus, Type 2, run by Jazz Pharmaceuticals at 25 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in Romania, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2022.