Study of the Gut Hormone Analogue Y14 in Adult Subjects

NCT03673111 | Completed Phase 1 Results DMC

• 2 other identifiers: ICIM/2016/Y14/012017-000380-33
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

A randomised, placebo controlled Phase I study to investigate investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of Y14 in adult subjects.

Conditions

Diabetes Mellitus; Obesity

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 73 days after dosing

Secondary Outcomes (4)

• Cmax

  For Part A, Cohorts A3 to A9 - up to 840 hour post dose. For Part B - up to day 70 post 1st dose

• AUC 0-72h

  Up to 72hr after dosing

• AUC 0-τ

  Up to 168h after dosing

• T 1/2

  For Part A, Cohorts A3 to A9 - up to 840 hour post dose. For Part B - up to day 70 post 1st dose

Study Arms (16)

1.0 mg Y14 (A1)

EXPERIMENTAL

Y14 single dose, subcutaneous

Drug: Y14

2.0 mg Y14 (A1)

EXPERIMENTAL

Y14 single dose, subcutaneous

Drug: Y14

6.0 mg Y14 (A1)

EXPERIMENTAL

Y14 single dose, subcutaneous

Drug: Y14

9.0 mg Y14 (A2) with varied formulation

EXPERIMENTAL

Y14 single dose, subcutaneous

Drug: Y14

18.0 mg Y14 (A5) with varied formulation

EXPERIMENTAL

Y14 single dose, subcutaneous

Drug: Y14

36.0 mg Y14 (A6) with varied formulation

EXPERIMENTAL

Y14 single dose, subcutaneous

Drug: Y14

Placebo (B)

PLACEBO COMPARATOR

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

Drug: Placebo

9-26.0 mg (B1)

EXPERIMENTAL

Y14 multiple dose, subcutaneous 5 doses over a 4 week treatment period: escalating doses to a max of 26 mg

Drug: Y14

9-36 mg (B2)

EXPERIMENTAL

Y14 multiple dose, subcutaneous 4 doses over a 4 week treatment period: escalating doses to a max of 36 mg

Drug: Y14

12-36 mg (B3)

EXPERIMENTAL

Y14 multiple dose, subcutaneous 4 doses over a 4 week treatment period: escalating doses to a max of 36 mg

Drug: Y14

Placebo (A)

PLACEBO COMPARATOR

Single subcutaneous injection of 0.9% saline

Drug: Placebo

9 mg Y14 (A3) with varied formulation

EXPERIMENTAL

Y14 single dose, subcutaneous

Drug: Y14

9 mg Y14 (A4) with varied formulation

EXPERIMENTAL

Y14 single dose, subcutaneous

Drug: Y14

18 mg Y14 (A7) with varied formulation

EXPERIMENTAL

Y14 single dose, subcutaneous

Drug: Y14

36 mg Y14 (A8) with varied formulation

EXPERIMENTAL

Y14 single dose, subcutaneous

Drug: Y14

36 mg Y14 (A9) with varied formulation

EXPERIMENTAL

Y14 single dose, subcutaneous

Drug: Y14

Interventions

Y14 DRUG

Gut hormone analogue

Also known as: Gut hormone analogue

1.0 mg Y14 (A1); 12-36 mg (B3); 18 mg Y14 (A7) with varied formulation; 18.0 mg Y14 (A5) with varied formulation; 2.0 mg Y14 (A1); 36 mg Y14 (A8) with varied formulation; 36 mg Y14 (A9) with varied formulation; 36.0 mg Y14 (A6) with varied formulation; 6.0 mg Y14 (A1); 9 mg Y14 (A3) with varied formulation; 9 mg Y14 (A4) with varied formulation; 9-26.0 mg (B1); 9-36 mg (B2); 9.0 mg Y14 (A2) with varied formulation

Placebo DRUG

0.9% saline

Also known as: Saline

Placebo (A); Placebo (B)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult males aged 18 to 65 years inclusive with BMI between 25.0 and 38.0 kg/m2 inclusive;
• (PART B only) Subjects who have normal glucose tolerance, Type 2 diabetes, impaired glucose tolerance or impaired fasting glucose according to WHO 2006 and 2011 criteria;
• 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 agree not to donate sperm 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 any of the following classes of diabetes medications: thiazolidinediones, dipeptidyl peptidase IV inhibitors ('gliptins'), GLP-1 analogues, and insulin;
• 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 glucocorticoids 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);
• Subjects who have a history of relevant drug hypersensitivity;
• Subjects who have a history of alcohol abuse or alcohol dependence according to DSMIV criteria within the last 2 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 to be treated for their diabetes with monotherapy with a sulphonylurea, metformin, or a SGLT-2 inhibitor, dual therapy with any two of the following drug types: a sulphonylurea, metformin, and/or a SGLT-2 inhibitor; triple therapy with a sulphonylurea, metformin, and a SGLT-2 inhibitor. 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

Related Publications (1)

• Tan TM, Minnion J, Khoo B, Ball LJ, Malviya R, Day E, Fiorentino F, Brindley C, Bush J, Bloom SR. Safety and efficacy of an extended-release peptide YY analogue for obesity: A randomized, placebo-controlled, phase 1 trial. Diabetes Obes Metab. 2021 Jul;23(7):1471-1483. doi: 10.1111/dom.14358. Epub 2021 Mar 9.

  PMID: 33606914 RESULT

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: Professor Tricia Tan
• Organization: Imperial College London

t.tan@imperial.ac.uk

020 8383 8038

Study Officials

• Stephen Bloom, FMedSci, FRS

  Sponsor Chief Investigator, Imperial College London

  STUDY DIRECTOR

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: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2018
• First Posted: September 17, 2018
• Study Start: April 10, 2017
• Primary Completion: February 13, 2019
• Study Completion: February 13, 2019
• Last Updated: March 18, 2025
• Results First Posted: March 18, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)