Diabetes Mellitus Obesity Nutritional, Metabolic, Endocrine
Conditions
Interventions
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 w
Sponsors
Imperial College London
Eligibility
Sex/Gender
Male
Inclusion criteria
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:
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability as assessed by: 1. Adverse events reported from the signing of the Informed Consent form until at least 5 half-lives or 7 days (whichever is longer) after the last dose of the study treatment 2. Vital signs: Blood pressure and pulse rate will be measured using an automated instrument with the subject in the supine position after resting comfortably for 10 minutes. Body temperature will be measured orally in degrees Celsius using an automated thermometer at screening and all inpatient and outpatient days. Additional monitoring can be added if deemed necessary for safety reasons 3. Physical examination performed by a physician and will include the examination of the following: general inspection chest/respiratory, heart/cardiovascular, gastrointestinal/liver, musculoskeletal/extremities, dermatological/ skin, thyroid/neck, lymph nodes, neurological/psychiatric at screening and all inpatient and outpatient visits. Additional monitoring can be added if deemed necessary for safety reasons 4. Clinical laboratory safety assessment is measured by the evaluation of blood and urine tests at screening and on every inpatient and outpatient study day. Additional and repeat testing may be performed at the discretion of the Principal Investigator 5. ECG parameters measured using computerised 12-lead ECG recordings after 5 minutes supine rest. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/sec. The following parameters will be recorded: ventricular rate, PR interval, QRS duration, QT and QTc | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics of the continuous subcutaneous infusion of G3215: PK parameters will be calculated using the data from the GLP qualified LC-MS/MS assay. Pharmacokinetic (PK) parameters of the G3215 when infused continuously subcutaneously will include observed maximum concentrations (Cmax), time of occurrence of Cmax (tmax), area under the plasma concentration-time curve over 24 hr (AUC0-24h). Attainment of steady state will be investigated by visual assessment of plasma concentrations on those days where the final dose is administered. | — |
Countries
England, United Kingdom
Outcome results
None listed