Overview

Study of the Gut Hormone Analogue Y14 in Adult Subjects

Status:
Completed
Trial end date:
2018-12-24
Target enrollment:
0
Participant gender:
Male
Summary
A randomised, placebo controlled Phase I study to investigate investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of Y14 in adult subjects.
Phase:
Phase 1
Accepts Healthy Volunteers?
Accepts Healthy Volunteers
Details
Lead Sponsor:
Imperial College London
Collaborators:
Covance
Medical Research Council
Criteria
Inclusion Criteria:

1. Adult males aged 18 to 65 years inclusive with BMI between 25.0 and 38.0 kg/m2
inclusive;

2. (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;

3. Subjects who are otherwise healthy enough to participate, as determined by pre-study
medical history, physical examination and 12-lead ECG;

4. 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;

5. Subjects who are negative for hepatitis B surface antigen (HBsAg), hepatitis C
antibody and human immunodeficiency virus (HIV) I and II tests at screening;

6. Subjects who are negative for drugs of abuse and alcohol tests at screening and
admissions;

7. Subjects who are non-smokers for at least 3 months preceding screening;

8. Subjects who agree to use medically acceptable methods of contraception for at least 3
months after study drug administration;

9. Subjects who agree not to donate sperm for at least 3 months after study drug
administration;

10. Subjects who are able and willing to give written informed consent.

Exclusion Criteria:

1. Subjects who do not conform to the above inclusion criteria;

2. 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;

3. Subjects who have a clinically relevant surgical history;

4. Subjects who are currently taking any of the following classes of diabetes
medications: thiazolidinediones, dipeptidyl peptidase IV inhibitors ('gliptins'),
GLP-1 analogues, and insulin;

5. 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);

6. Subjects who have a history of relevant drug hypersensitivity;

7. Subjects who have a history of alcohol abuse or alcohol dependence according to DSMIV
criteria within the last 2 years;

8. Subjects who have a history of drug or substance abuse according to DSM-IV criteria
within the last 2 years;

9. 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;

10. Subjects with a history of pancreatitis or pancreatic cancer;

11. 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);

12. Subjects who have a significant infection or known inflammatory process on screening;

13. Subjects who have acute gastrointestinal symptoms at the time of screening or
admission (e.g. nausea, vomiting, diarrhoea, heartburn);

14. Subjects who have an acute infection such as influenza at the time of screening or
admission;

15. 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.

16. 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;

17. 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

18. Subjects who have used any investigational drug in any clinical trial within 3 months
of their first admission date;

19. Subjects who have received the last dose of investigational drug greater than 3 months
ago but who are on extended follow-up;

20. Subjects who have previously received Y14;

21. Subjects who are vegans, vegetarian or have any dietary restriction (unless agreed as
not clinically relevant by the PI and Sponsors);

22. Subjects who cannot communicate reliably with the Investigator;

23. Subjects who are unlikely to co-operate with the requirements of the study;

24. History or evidence of abnormal eating behaviour, as observed through the Dutch Eating
Behaviour (DEBQ) and SCOFF questionnaires at screening.