Safety and Pharmacokinetic Study of Y242 in Adult Subjects
Condition: Obesity
MeSH terms: Obesity
Intervention: Y242; 0.9% saline
Intervention description: Single ascending dose: subcutaneous injection of 2, 7.5, 15, 30, 60 and 90 mg Y242 (Part A); Multiple ascending dose: Y242 single subcutaneous dose, administered once a week for 5 weeks (Part B); Identical volume to that of Y242
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Part A was a single blind, randomised, placebo controlled, single ascending dose (SAD) study.
Part B was a double blind, randomised, placebo controlled, multiple ascending dose (MAD) study
Masking: Double (Participant, Investigator)
Masking description: Part A: Treatments were administered single-blind; subjects were blinded with regard to treatment and clinical staff remained blinded with regard to treatment until the Safety Committee meeting. Part B was double blind.
Enrollment: 68.0
Sex: Male
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Obesity; Peptide YY; Food intake; Safety; Pharmacokinetics

Summary:

      Obesity causes 600 premature deaths per week in the UK and existing treatments are not
      effective. When humans eat, the bowels naturally secrete chemicals into the bloodstream which
      make people feel full and which stop eating. One of these chemicals is known as Peptide YY
      (PYY). The investigators have previously shown that injections of PYY reduce appetite and
      food intake in human volunteers. The investigators have now developed a very similar
      chemical, Y242, as a treatment for obesity. Y242 has been tested in animals and has been
      shown to be safe, to reduce their appetite, and to last for much longer than PYY itself. This
      study will test Y242 to ensure that it is well tolerated in humans, and to see how long it
      lasts in the blood stream after being injected under the skin. It will also look for any
      effects on appetite.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult males aged 18 to 50 years inclusive with BMI between 23.0 and 30.0 kg/m^2
             inclusive;

          -  Subjects who are healthy 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 have a clinically relevant family history;

          -  Subjects who have a history of relevant atopy;

          -  Subjects who have a history of relevant drug hypersensitivity;

          -  Subjects who have a history of alcoholism;

          -  Subjects who have a history of drug abuse;

          -  Subjects who have a history of migraine;

          -  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 4 weeks of first dosing;

          -  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;

          -  Subjects who have donated blood or blood products within 3 months of Day -2
             (admission);

          -  Subjects who have used any investigational drug in any clinical trial within 3 months
             of Day -2 (admission);

          -  Subjects who have received the last dose of investigational drug greater than 3 months
             ago but who are on extended follow-up;

          -  Subjects who have previously received Y242;

          -  Subjects who are vegans or have any dietary restrictions;

          -  Subjects who cannot communicate reliably with the Investigator;

          -  Subjects who are unlikely to co-operate with the requirements of the study;

          -  History or evidence of abnormal eating behaviour, as observed through the Dutch Eating
             Behaviour (DEBQ) and SCOFF questionnaires at screening.