Testing the safety and effects of a new drug (G3215) in adult subjects
| ISRCTN | ISRCTN67889041 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN67889041 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | 2020-000051-12 |
| Integrated Research Application System (IRAS) | 278196 |
| Protocol serial number | IRAS 278196 |
| Sponsor | Imperial College London |
| Funder | Imperial College Healthcare NHS Trust: Division of Women’s, Children’s and Clinical Support |
- Submission date
- 23/10/2020
- Registration date
- 03/11/2020
- Last edited
- 18/01/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
Background and study aims
Obesity (defined as a BMI of more than 30 kg/m2) reduces life expectancy and increases the incidence of cardiovascular disease, diabetes, certain cancers, and depression. Medicinal approaches for obesity treatment have recently focused on looking at the hormonal regulation of appetite. The level of appetite in our bodies is controlled by peptide hormones which are released in the gut, such as oxyntomodulin (OXM).
OXM reduces appetite and food intake and increases the amount of energy the body uses. OXM is also known to increase the release of insulin (a hormone that helps control the levels of sugar in the body). The Study Drug, G3215, is chemically similar to OXM and is being investigated as a potential treatment for obesity and diabetes.
Who can participate?
Males aged 18 to 65 with a body mass index (BMI) between 25 and 38 kg/m² with either normal blood glucose levels, pre-diabetes or diabetes will be invited to participate in the study.
What does the study involve?
All participants will receive either the Study Drug or a placebo (saline), administered through an infusion pump (in the abdomen) continuously over a period of 14 days. The doses will vary depending on the group of participants, but will be administered incrementally (starting off at a low dose). As well as examining how safe and tolerable the Study Drug is, we will assess the participants blood glucose, body weight, energy intake and food intake. Participants will be invited back for follow up assessments to see when the Study Drug has cleared from their blood stream.
What are the possible benefits and risks of participating?
There will be no direct benefit from participating in the study. There will be no continued provision of any Study Drug or health intervention after the end of the study as the Study Drug is still being investigated for its safety. Although there may be no direct benefits of taking part, the results may lead to development of a treatment for obesity. Expected side effects of the Study Drug include temporary nausea and vomiting, and possibly skin reactions from wearing the pump or from taking blood samples.
Where is the study run from?
The study will be run from the NIHR/Wellcome Trust Imperial Clinical Research Facility (CRF) at the Hammersmith Hospital (UK). The study team is located at the Division of Metabolism, Digestion and Reproduction, Imperial College London at Hammersmith Hospital (UK).
When is the study starting and how long is it expected to run for?
January 2020 to October 2021
Who is funding the study?
The trial is being funded by a Divisional Research Funding Award from the Division of Women’s, Children’s and Clinical Support at Imperial College Healthcare NHS Trust, London (UK).
Who is the main contact?
Professor Tricia Tan, t.tan@imperial.ac.uk.
Contact information
Scientific
Imperial College London
Hammersmith Campus
Du Cane Road
London
W12 0NN
United Kingdom
 ORCID ID |
0000-0001-5873-3432 |
|---|---|
| Phone | +44 (0)20 3313 8038 |
| t.tan@imperial.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Double blind randomised placebo controlled ascending dose study in sequential groups at a single site |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | A randomised, placebo controlled study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of an Oxyntomodulin analogue (G3215) delivered via a subcutaneous infusion in adult subjects |
| Study objectives | To investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of G3215 in adult subjects |
| Ethics approval(s) | Approved 09/06/2020, London - West London & GTAC Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, UK; +44 (0)207 1048 007; westlondon.rec@hra.nhs.uk), ref: 20/LO/0411 |
| Health condition(s) or problem(s) studied | Diabetes Mellitus Obesity |
| Intervention | Subjects will be randomised to 14 days of G3215 or placebo administered by continuous SC infusion over 14 days. The G3215 doses will be increased every 12/24 hours over the first four days, starting with 0.6 mg/24 hr in the first cohort. Allocation to treatment will be according to a predetermined random order. The randomisation list will be generated using the Oracle Inform data capture system. This is a double-blind study. Randomisation of G3215 or placebo will take place for each group separately. The pair of sentinel subjects in Cohort 1 will be randomised such that 1 subject receives G3215 and 1 receives placebo. |
| Intervention type | Drug |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | G3215 0.9% Saline [w/v] (placebo) |
| Primary outcome measure(s) |
Safety and tolerability as assessed by: |
| Key secondary outcome measure(s) |
Pharmacokinetics of the continuous subcutaneous infusion of G3215: |
| Completion date | 22/10/2021 |
Eligibility
| Participant type(s) | Mixed |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Male |
| Target sample size at registration | 24 |
| Key inclusion criteria | Current inclusion criteria as of 07/09/2021: 1. Adult males aged 18 to 65 years inclusive with BMI between 25.0 and 45.0 kg/m² inclusive 2. Subjects may have normal glucose tolerance, Type 2 diabetes, impaired glucose tolerance or impaired fasting glucose according to WHO 2006 and 2011 criteria 3. The following criteria apply to subjects with Type 2 diabetes, impaired glucose tolerance or impaired fasting glucose according to WHO 2006 and 2011 criteria 3.1. They should be stably treated either with: 3.1.1. Diet and lifestyle changes only 3.1.2. Monotherapy with a sulphonylurea, metformin, or SGLT-2 inhibitor; or 3.1.3. Dual therapy with sulphonylurea/metformin, or sulphonylurea/SGLT-2 inhibitor 3.2. Patients treated with triple anti-diabetic treatments are excluded 3.3. The HbA1c at screening should be 6.0–8.5% (42–69 mmol/mol) and <±1.0% (±11 mmol/mol) from a previous HbA1c reading within the last 6 months, where available. Where an HbA1c reading within the last 6 months is not available, the subject should have HbA1c re-measured after at least 4 weeks to assure stability of glycaemia before inclusion in the study. This remeasurement may take place any time up to and including check in on Day -1 3.4. To allow assessment of eligibility, subjects without known diabetes or prediabetes, or in whom the glycaemic status is in doubt, may undergo a pre-screening visit no more than 10 weeks before Day 1 for assessment of fasting glucose, HbA1c and glucose 2 hours after a 75 g oral glucose tolerance test 4. Subjects who are otherwise healthy enough to participate, as determined by pre-study medical history, physical examination and 12-lead ECG 5. Subjects whose clinical laboratory test results are either within the normal range or if outside this range the abnormalities are judged to be not clinically relevant and are acceptable to the Investigator 6. Subjects who are negative for hepatitis B surface antigen (HBsAg), hepatitis C antibody test and human immunodeficiency virus (HIV) I and II antibody tests at screening 7. Subjects who are negative for drugs of abuse and nicotine tests at screening and admissions 8. Subjects who do not take nicotine (including consumption of tobacco by any means or use of nicotine delivery systems) for at least 3 months preceding screening 9. Subjects who agree to use acceptable methods of contraception (see 7.2.3.1 and 7.2.3.2) for at least 3 months after study drug administration 10. Subjects who agree not to donate sperm for at least 3 months after study drug administration 11. Subjects who are able and willing to give written informed consent Previous inclusion criteria: 1. Adult males aged 18 to 65 years inclusive with BMI between 25.0 and 38.0 kg/m² inclusive 2. Subjects may have normal glucose tolerance, Type 2 diabetes, impaired glucose tolerance or impaired fasting glucose according to WHO 2006 and 2011 criteria 3. The following criteria apply to subjects with Type 2 diabetes, impaired glucose tolerance or impaired fasting glucose according to WHO 2006 and 2011 criteria 4. They should be stably treated either with: 4.1. Diet and lifestyle changes only 4.2. Monotherapy with a sulphonylurea, metformin, or SGLT-2 inhibitor or 4.3. Dual therapy with sulphonylurea/metformin, or sulphonylurea/SGLT-2 inhibitor 4.4. Patients treated with triple anti-diabetic treatments are excluded 5. The HbA1c at screening should be 6.0–8.5% (42–69 mmol/mol) and <±1.0% (±11 mmol/mol) from a previous HbA1c reading within the last 6 months, where available. Where an HbA1c reading within the last 6 months is not available, the subject should have HbA1c re-measured after at least 4 weeks to assure stability of glycaemia before inclusion in the study. This remeasurement may take place any time up to and including check in on Day -1 6. To allow assessment of eligibility, subjects without known diabetes or prediabetes, or in whom the glycaemic status is in doubt, may undergo a pre-screening visit no more than 10 weeks before Day 1 for assessment of fasting glucose, HbA1c and glucose 2 hours after a 75 g oral glucose tolerance test 7. Subjects who are otherwise healthy enough to participate, as determined by pre-study medical history, physical examination and 12 lead ECG 8. Subjects whose clinical laboratory test results are either within the normal range or if outside this range the abnormalities are judged to be not clinically relevant and are acceptable to the Investigator 9. Subjects who are negative for hepatitis B surface antigen (HBsAg), hepatitis C antibody test and human immunodeficiency virus (HIV) I and II antibody tests at screening 10. Subjects who are negative for drugs of abuse, nicotine and alcohol tests at screening and admissions 11. Subjects who do not take nicotine (including consumption of tobacco by any means or use of nicotine delivery systems) for at least 3 months preceding screening 12. Subjects who agree to use acceptable methods of contraception for at least 3 months after study drug administration 13. Subjects who agree not to donate sperm for at least 3 months after study drug administration 14. Subjects who are able and willing to give written informed consent |
| Key exclusion criteria | 1. Subjects who do not conform to the above inclusion criteria 2. Subjects who have a relevant history or presence of gastrointestinal (especially associated with vomiting), respiratory, renal, hepatic, haematological, lymphatic, neurological (especially if associated with balance disorders or vomiting e.g. migraine or labyrinthitis), cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders that in the Investigator’s opinion will compromise safety, practicability or scientific value of the study 3. Subjects who have a relevant surgical history that in the Investigator’s opinion will compromise safety, practicability or scientific value of the study 4. Subjects who have used prescription drugs within 4 weeks of first dosing, with the following exceptions: a. Anti-diabetic drugs as specified in the inclusion criteria. b. Hypolipidaemic and/or antihypertensive treatments, provided that the doses have not been altered within the 4 weeks prior to entering the study. c. Other medications may be allowed if the Investigator judges that they will not affect the outcome of the study or the safety of the subject. 5. Subjects who have used over the counter medication excluding routine vitamins and paracetamol but including megadose (intake of 20 to 600 times the recommended daily dose) vitamin therapy within 7 days of first dosing, unless agreed as not clinically relevant by the Investigator and Sponsor 6. Subjects who have a history of relevant and severe atopy e.g. asthma, angioedema requiring emergency treatment, severe hayfever requiring regular treatment (i.e. taking antihistamines and/or glucorticoids more regularly than 3 times a week), severe eczema requiring regular treatment (i.e. taking antihistamines and/or glucocorticoids more regularly than 3 times a week) 7. Subjects who have a history of relevant drug hypersensitivity 8. Subjects who have a history of alcohol abuse or alcohol dependence according to DSM-IV criteria within the last two years 9. Subjects who have a history of drug or substance abuse according to DSM-IV criteria within the last 2 years 10. Subjects who have a history of clinically significant migraine as judged by the Investigator. Subjects can be included if they have not had a migraine for the last 3 years 11. Subjects with a history of pancreatitis or pancreatic cancer 12. Subjects who consume more than 21 units of alcohol a week (unit = 1 glass of wine (125 mL) = 1 measure of spirits = ½ pint of beer) 13. Subjects who have a significant infection or known inflammatory process on screening 14. Subjects who have acute gastrointestinal symptoms at the time of screening or admission (e.g. nausea, vomiting, diarrhoea, heartburn) 15. Subjects who have an acute infection such as influenza at the time of screening or admission 16. Subjects who have donated blood within 3 months prior to screening 17. Subjects who have donated plasma within the 7 days prior to screening 18. Subjects who have donated platelets within the 6 weeks prior to screening 19. Subjects who have used any investigational drug in any clinical trial within 3 months of their first admission date 20. Subjects who have received the last dose of investigational drug greater than 3 months ago but who are on extended follow-up 21. Subjects who have previously received G3215 22. Subjects who have any dietary restrictions that, in the opinion of the Investigator, will compromise the safety, practicability or scientific value of the study 23. Subjects who cannot communicate reliably with the Investigator 24. Subjects who are unlikely to co-operate with the requirements of the study 25. History or evidence of abnormal eating behaviour, as observed through the Dutch Eating Behaviour (DEBQ) and SCOFF questionnaires at screening |
| Date of first enrolment | 02/11/2020 |
| Date of final enrolment | 22/09/2021 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
Imperial Centre for Translational and Experimental Medicine
London
W12 0HS
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Other |
| IPD sharing plan | All data generated or analysed during this study will be included in the subsequent results publication |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 16/01/2024 | 18/01/2024 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
18/01/2024: Publication reference added.
07/09/2021: The inclusion criteria were updated.
27/10/2020: Trial’s existence confirmed by London - West London & GTAC Research Ethics Committee.
