A Randomised, Placebo Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Gut Hormone Analogue G3215 in Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- Placebo
- Conditions
- Diabetes Mellitus
- Sponsor
- Imperial College London
- Enrollment
- 90
- Locations
- 1
- Primary Endpoint
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability]
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
A randomised, placebo controlled Phase I study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of G3215 in adult subjects.
Detailed Description
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.
Investigators
Eligibility Criteria
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;
Arms & Interventions
Placebo (B) - saline
5 subcutaneous injections of 0.9% saline, over a 4 week treatment period
Intervention: Placebo
4 mg dose G3215 (A2) with varied formulation
4 mg G3215 single dose, subcutaneous injection
Intervention: G3215
12-24 mg (B1) dose of G3215
G3215 multiple dose, subcutaneous injection: 5 doses over a 4 week treatment period at escalating doses to a max of 24 mg.
Intervention: G3215
6-10 mg (B2) dose of G3215
G3215 multiple dose, subcutaneous injection: 5 doses over a 4 week treatment period at escalating doses to a max of 10 mg.
Intervention: G3215
5-16 mg (B3) dose of G3215
G3215 multiple dose, subcutaneous injection: 5 doses over a 4 week treatment period at escalating doses to a max of 16 mg.
Intervention: G3215
3.2mg (C) infusion pump dose of G3215
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 \[saline\]).
Intervention: G3215
3.2mg (C) infusion pump dose of G3215
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 \[saline\]).
Intervention: Placebo
Placebo (A) - saline
Single subcutaneous injection of 0.9% saline
Intervention: Placebo
0.1 mg dose G3215 (A1)
0.1 mg G3215 single dose, subcutaneous injection
Intervention: G3215
0.5 mg dose G3215 (A1)
0.5 mg G3215 single dose, subcutaneous injection
Intervention: G3215
1.5 mg dose G3215 (A1)
1.5 mg G3215 single dose, subcutaneous injection
Intervention: G3215
4 mg dose G3215 (A3) with varied formulation
4 mg G3215 single dose, subcutaneous injection
Intervention: G3215
4 mg dose G3215 (A4) with varied formulation
4 mg G3215 single dose, subcutaneous injection
Intervention: G3215
4 mg dose G3215 (A5) with varied formulation
4 mg G3215 single dose, subcutaneous injection
Intervention: G3215
8 mg dose G3215 (A7)
8 mg G3215 single dose, subcutaneous injection
Intervention: G3215
10 mg dose G3215 (A6)
10 mg G3215 single dose, subcutaneous injection
Intervention: G3215
12 mg dose G3215 (A8)
12 mg G3215 single dose, subcutaneous injection
Intervention: G3215
16 mg dose G3215 (A9)
16 mg G3215 single dose, subcutaneous injection
Intervention: G3215
32 mg dose G3215 (A10)
32 mg G3215 single dose, subcutaneous injection
Intervention: G3215
48 mg dose G3215 (A11)
48 mg G3215 single dose, subcutaneous injection
Intervention: G3215
Outcomes
Primary Outcomes
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability]
Time Frame: up to 28 days after dosing
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
Secondary Outcomes
- Body Weight (Percentage Change From Baseline)(up to day 4 (am) for Part A, day 31 (pm) for Part B and day 5 (am) for Part C)