Study of the Gut Hormone Analogue G3215 in Adult Subjects

NCT02692040 | Completed Phase 1 Results DMC

• 1 other identifier: 2014/G3215/01
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Diabetes Mellitus; Obesity

Keywords

obesity; diabetes mellitus; glucagon-like peptide-1

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Study Arms (19)

12-24 mg (B1) dose of G3215

EXPERIMENTAL

G3215 multiple dose, subcutaneous injection: 5 doses over a 4 week treatment period at escalating doses to a max of 24 mg.

Drug: G3215

6-10 mg (B2) dose of G3215

EXPERIMENTAL

G3215 multiple dose, subcutaneous injection: 5 doses over a 4 week treatment period at escalating doses to a max of 10 mg.

Drug: G3215

5-16 mg (B3) dose of G3215

EXPERIMENTAL

G3215 multiple dose, subcutaneous injection: 5 doses over a 4 week treatment period at escalating doses to a max of 16 mg.

Drug: G3215

3.2mg (C) infusion pump dose of G3215

EXPERIMENTAL

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; Drug: Placebo

Placebo (B) - saline

PLACEBO COMPARATOR

5 subcutaneous injections of 0.9% saline, over a 4 week treatment period

Drug: Placebo

Placebo (A) - saline

PLACEBO COMPARATOR

Single subcutaneous injection of 0.9% saline

Drug: Placebo

0.1 mg dose G3215 (A1)

EXPERIMENTAL

0.1 mg G3215 single dose, subcutaneous injection

Drug: G3215

0.5 mg dose G3215 (A1)

EXPERIMENTAL

0.5 mg G3215 single dose, subcutaneous injection

Drug: G3215

1.5 mg dose G3215 (A1)

EXPERIMENTAL

1.5 mg G3215 single dose, subcutaneous injection

Drug: G3215

4 mg dose G3215 (A2) with varied formulation

EXPERIMENTAL

4 mg G3215 single dose, subcutaneous injection

Drug: G3215

4 mg dose G3215 (A3) with varied formulation

EXPERIMENTAL

4 mg G3215 single dose, subcutaneous injection

Drug: G3215

4 mg dose G3215 (A4) with varied formulation

EXPERIMENTAL

4 mg G3215 single dose, subcutaneous injection

Drug: G3215

4 mg dose G3215 (A5) with varied formulation

EXPERIMENTAL

4 mg G3215 single dose, subcutaneous injection

Drug: G3215

8 mg dose G3215 (A7)

EXPERIMENTAL

8 mg G3215 single dose, subcutaneous injection

Drug: G3215

10 mg dose G3215 (A6)

EXPERIMENTAL

10 mg G3215 single dose, subcutaneous injection

Drug: G3215

12 mg dose G3215 (A8)

EXPERIMENTAL

12 mg G3215 single dose, subcutaneous injection

Drug: G3215

16 mg dose G3215 (A9)

EXPERIMENTAL

16 mg G3215 single dose, subcutaneous injection

Drug: G3215

32 mg dose G3215 (A10)

EXPERIMENTAL

32 mg G3215 single dose, subcutaneous injection

Drug: G3215

48 mg dose G3215 (A11)

EXPERIMENTAL

48 mg G3215 single dose, subcutaneous injection

Drug: G3215

Interventions

G3215 DRUG

Gut hormone analogue

0.1 mg dose G3215 (A1); 0.5 mg dose G3215 (A1); 1.5 mg dose G3215 (A1); 10 mg dose G3215 (A6); 12 mg dose G3215 (A8); 12-24 mg (B1) dose of G3215; 16 mg dose G3215 (A9); 3.2mg (C) infusion pump dose of G3215; 32 mg dose G3215 (A10); 4 mg dose G3215 (A2) with varied formulation; 4 mg dose G3215 (A3) with varied formulation; 4 mg dose G3215 (A4) with varied formulation; 4 mg dose G3215 (A5) with varied formulation; 48 mg dose G3215 (A11); 5-16 mg (B3) dose of G3215; 6-10 mg (B2) dose of G3215; 8 mg dose G3215 (A7)

Placebo DRUG

0.9% saline

Also known as: Saline

3.2mg (C) infusion pump dose of G3215; Placebo (A) - saline; Placebo (B) - saline

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Imperial College London: lead
• Medical Research Council: collaborator
• Covance: collaborator

Study Sites (1)

Covance Clinical Research Unit

Leeds, LS2 9LH, United Kingdom

Location

MeSH Terms

Conditions

Diabetes Mellitus; Obesity

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Dr Tricia Tan
• Organization: Imperial College London

t.tan@imperial.ac.uk

020 838 38038

Study Officials

• Jim Bush, PhD MRCS

  Covance Clinical Research Unit

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2016
• First Posted: February 25, 2016
• Study Start: January 1, 2015
• Primary Completion: January 1, 2019
• Study Completion: January 1, 2019
• Last Updated: December 23, 2020
• Results First Posted: December 23, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)