Study of the Gut Hormone Analogue G3215 in Adult Subjects

Study Overview
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Brief Summary
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A randomised, placebo controlled Phase I study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of G3215 in adult subjects.

Detailed Description
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Objectives: Primary Objective To investigate the safety and tolerability of single doses of G3215 in overweight but otherwise healthy male subjects. To investigate the safety and tolerability of multiple doses of G3215 in overweight male subjects with mild stable Type 2 diabetes or prediabetes. Secondary Objectives • To assess the pharmacokinetic (PK) profile of single and multiple ascending doses of G3215 in overweight but otherwise healthy male subjects or overweight / obese male subjects with mild stable Type 2 diabetes or prediabetes. Exploratory Objective • To investigate the effects of multiple doses of G3215 on food consumption, body weight, enteropancreatic hormone changes and glucose tolerance in overweight male subjects with mild Type 2 diabetes or prediabetes.

Official Title
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A Randomised, Placebo Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Gut Hormone Analogue G3215 in Adult Subjects

Conditions
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Diabetes Mellitus, Obesity

Intervention / Treatment
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* Drug: G3215
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult males aged 18 to 60 years inclusive with body mass index (BMI) between 25.0 and 35.0 kg/m2 inclusive; Subjects who are otherwise healthy enough to participate, as determined by pre-study medical history, physical examination and 12 lead ECG; 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; Subjects who are negative for hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) I and II tests at screening; Subjects who are negative for drugs of abuse and alcohol tests at screening and admissions; Subjects who are non-smokers for at least 3 months preceding screening; Subjects who agree to use medically acceptable methods of contraception for at least 3 months after study drug administration; Subjects who are able and willing to give written informed consent. Exclusion Criteria: Subjects who do not conform to the above inclusion criteria; Subjects who have a clinically 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; Subjects who have a clinically relevant surgical history; Subjects who are currently taking thiazolidinediones, dipeptidyl peptidase IV inhibitors ('gliptins'), glucagon-like peptide-1 (GLP-1) analogues, sodium-glucose co-transporter (SGLT-2) inhibitors, and insulin; Subjects who have a history of relevant and severe atopy e.g. asthma, angioedema requiring emergency treatment, severe hayfever requiring regular treatment, severe eczema requiring regular treatment; Subjects who have a history of relevant drug hypersensitivity; Subjects who have a history of alcohol abuse or alcohol dependence according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria within the last two years; Subjects who have a history of drug or substance abuse according to DSM-IV criteria within the last 2 years; 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; Subjects with a history of pancreatitis or pancreatic cancer; 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); Subjects who have a significant infection or known inflammatory process on screening; Subjects who have acute gastrointestinal symptoms at the time of screening or admission (e.g. nausea, vomiting, diarrhoea, heartburn); Subjects who have an acute infection such as influenza at the time of screening or admission; Subjects who have used prescription drugs within 2 weeks of first dosing. For Part B, patients are allowed; monotherapy with sulphonylureas, or metformin. In addition patients in Part B are allowed to take hypolipidaemic and/or antihypertensive treatments, provided that the doses have not been altered within the 4 weeks prior to entering the study. Other medications may be allowed if the Investigator and Sponsor both agree that they will not affect the outcome of the study or the safety of the subject. 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 Principal Investigator and Sponsor; Subjects who have donated blood within 3 months prior to screening; Subjects who have donated plasma within the 7 days prior to screening; Subjects who have donated platelets within the 6 weeks prior to screening Subjects who have used any investigational drug in any clinical trial within 3 months of their first admission date; Subjects who have received the last dose of investigational drug greater than 3 months ago but who are on extended follow-up; Subjects who have previously received G3215; Subjects who are vegans or have any dietary restrictions; Subjects who cannot communicate reliably with the Investigator; Subjects who are unlikely to co-operate with the requirements of the study; History or evidence of abnormal eating behaviour, as observed through the Dutch Eating Behaviour (DEBQ) and SCOFF (Sick, Control, One Stone, Fat, Food) questionnaires at screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 12-24 mg (B1) dose of G3215<br>G3215 multiple dose, subcutaneous injection: 5 doses over a 4 week treatment period at escalating doses to a max of 24 mg. | Drug: G3215<br>* Gut hormone analogue<br>|
| Experimental: 6-10 mg (B2) dose of G3215<br>G3215 multiple dose, subcutaneous injection: 5 doses over a 4 week treatment period at escalating doses to a max of 10 mg. | Drug: G3215<br>* Gut hormone analogue<br>|
| Experimental: 5-16 mg (B3) dose of G3215<br>G3215 multiple dose, subcutaneous injection: 5 doses over a 4 week treatment period at escalating doses to a max of 16 mg. | Drug: G3215<br>* Gut hormone analogue<br>|
| Experimental: 3.2mg (C) infusion pump dose of G3215<br>G3215 subcutaneous infusion over a 4 day treatment period at escalating doses to a max of 3.2 mg (with either the first or last day administering infusion of placebo [saline]). | Drug: G3215<br>* Gut hormone analogue<br>Drug: Placebo<br>* 0.9% saline<br>* Other names: Saline;|
| Placebo Comparator: Placebo (B) - saline<br>5 subcutaneous injections of 0.9% saline, over a 4 week treatment period | Drug: Placebo<br>* 0.9% saline<br>* Other names: Saline;|
| Placebo Comparator: Placebo (A) - saline<br>Single subcutaneous injection of 0.9% saline | Drug: Placebo<br>* 0.9% saline<br>* Other names: Saline;|
| Experimental: 0.1 mg dose G3215 (A1)<br>0.1 mg G3215 single dose, subcutaneous injection | Drug: G3215<br>* Gut hormone analogue<br>|
| Experimental: 0.5 mg dose G3215 (A1)<br>0.5 mg G3215 single dose, subcutaneous injection | Drug: G3215<br>* Gut hormone analogue<br>|
| Experimental: 1.5 mg dose G3215 (A1)<br>1.5 mg G3215 single dose, subcutaneous injection | Drug: G3215<br>* Gut hormone analogue<br>|
| Experimental: 4 mg dose G3215 (A2) with varied formulation<br>4 mg G3215 single dose, subcutaneous injection | Drug: G3215<br>* Gut hormone analogue<br>|
| Experimental: 4 mg dose G3215 (A3) with varied formulation<br>4 mg G3215 single dose, subcutaneous injection | Drug: G3215<br>* Gut hormone analogue<br>|
| Experimental: 4 mg dose G3215 (A4) with varied formulation<br>4 mg G3215 single dose, subcutaneous injection | Drug: G3215<br>* Gut hormone analogue<br>|
| Experimental: 4 mg dose G3215 (A5) with varied formulation<br>4 mg G3215 single dose, subcutaneous injection | Drug: G3215<br>* Gut hormone analogue<br>|
| Experimental: 8 mg dose G3215 (A7)<br>8 mg G3215 single dose, subcutaneous injection | Drug: G3215<br>* Gut hormone analogue<br>|
| Experimental: 10 mg dose G3215 (A6)<br>10 mg G3215 single dose, subcutaneous injection | Drug: G3215<br>* Gut hormone analogue<br>|
| Experimental: 12 mg dose G3215 (A8)<br>12 mg G3215 single dose, subcutaneous injection | Drug: G3215<br>* Gut hormone analogue<br>|
| Experimental: 16 mg dose G3215 (A9)<br>16 mg G3215 single dose, subcutaneous injection | Drug: G3215<br>* Gut hormone analogue<br>|
| Experimental: 32 mg dose G3215 (A10)<br>32 mg G3215 single dose, subcutaneous injection | Drug: G3215<br>* Gut hormone analogue<br>|
| Experimental: 48 mg dose G3215 (A11)<br>48 mg G3215 single dose, subcutaneous injection | Drug: G3215<br>* Gut hormone analogue<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability] | As assessed by reporting of adverse events, vital signs, physical examination, clinical laboratory safety assessments, and ECG parameters. Possibly or definitely related to study drug | up to 28 days after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Weight (Percentage Change From Baseline) | Summary of Time-Matched % Change from Baseline in Body Weight (AM Baseline = Day 1 AM; PM Baseline = Day -1 PM | up to day 4 (am) for Part A, day 31 (pm) for Part B and day 5 (am) for Part C | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obesity, diabetes mellitus, glucagon-like peptide-1