A Randomised, Placebo Controlled First in Human Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Y14 in Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- Y14
- Conditions
- Diabetes Mellitus
- Sponsor
- Imperial College London
- Enrollment
- 77
- Locations
- 1
- Primary Endpoint
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (Safety and Tolerability)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
A randomised, placebo controlled Phase I study to investigate investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of Y14 in adult subjects.
Detailed Description
Objectives: Primary Objective * To investigate the safety and tolerability of single doses of Y14 in overweight/obese but otherwise healthy male subjects. * To investigate the safety and tolerability of multiple doses of Y14 in overweight/obese male subjects with normal glucose tolerance, Type 2 diabetes or prediabetes. Secondary Objectives * To assess the pharmacokinetic (PK) profile of single doses of Y14 in overweight/obese but otherwise healthy male subjects. * To assess the PK profile of multiple ascending doses of Y14 in overweight/obese male subjects with normal glucose tolerance, Type 2 diabetes or prediabetes. Exploratory Objective * To investigate the effects of multiple doses of Y14 on food consumption, body weight and glucose tolerance in overweight/obese male subjects with normal glucose tolerance, Type 2 diabetes or prediabetes.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
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 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;
Arms & Interventions
18.0 mg Y14 (A5) with varied formulation
Y14 single dose, subcutaneous
Intervention: Y14
1.0 mg Y14 (A1)
Y14 single dose, subcutaneous
Intervention: Y14
2.0 mg Y14 (A1)
Y14 single dose, subcutaneous
Intervention: Y14
6.0 mg Y14 (A1)
Y14 single dose, subcutaneous
Intervention: Y14
9.0 mg Y14 (A2) with varied formulation
Y14 single dose, subcutaneous
Intervention: Y14
36.0 mg Y14 (A6) with varied formulation
Y14 single dose, subcutaneous
Intervention: Y14
Placebo (B)
5 subcutaneous injections of 0.9% saline, over a 4 week treatment period
Intervention: Placebo
9-26.0 mg (B1)
Y14 multiple dose, subcutaneous 5 doses over a 4 week treatment period: escalating doses to a max of 26 mg
Intervention: Y14
9-36 mg (B2)
Y14 multiple dose, subcutaneous 4 doses over a 4 week treatment period: escalating doses to a max of 36 mg
Intervention: Y14
12-36 mg (B3)
Y14 multiple dose, subcutaneous 4 doses over a 4 week treatment period: escalating doses to a max of 36 mg
Intervention: Y14
Placebo (A)
Single subcutaneous injection of 0.9% saline
Intervention: Placebo
9 mg Y14 (A3) with varied formulation
Y14 single dose, subcutaneous
Intervention: Y14
9 mg Y14 (A4) with varied formulation
Y14 single dose, subcutaneous
Intervention: Y14
18 mg Y14 (A7) with varied formulation
Y14 single dose, subcutaneous
Intervention: Y14
36 mg Y14 (A8) with varied formulation
Y14 single dose, subcutaneous
Intervention: Y14
36 mg Y14 (A9) with varied formulation
Y14 single dose, subcutaneous
Intervention: Y14
Outcomes
Primary Outcomes
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (Safety and Tolerability)
Time Frame: Up to 73 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
- 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)