Safety and Pharmacokinetic Study of Y242 in Adult Subjects
Condition: Obesity
MeSH terms: Obesity
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      Obesity causes 600 premature deaths per week in the UK and existing treatments are less than
      ideal. Intravenous infusion of a hormone called PYY reduces food intake but its effects only
      last for a few hours and it can cause nausea. Y242 is a longacting analogue of PYY. Given
      subcutaneously in rodents, it has a profile of action of at least 72 hours and strongly
      inhibits food intake. It causes weight loss without behavioural effects. With MRC funding,
      Y242 has passed Good Laboratory Practice toxicology testing and the present proposal is a
      first in human study to investigate its safety, tolerability and pharmacokinetics in
      overweight but otherwise healthy men.

      The study is a combined single ascending dose (part A) and multiple ascending dose (part B)
      Phase 1 investigation. The primary objective is to investigate safety and tolerability. The
      secondary objective is to assess Y242's pharmacokinetic (PK) profile. Possible effects on
      food consumption will be explored. For part A up to 48 subjects are planned, with up to 40
      subjects for part B. In each part subjects are divided into groups, each of which is dosed
      with the same level, starting with a single dose (part A) much lower than is expected to
      cause an effect. Subjects are admitted to a Unit so they can be closely observed for adverse
      effects and safety tests, blood concentrations of the drug and food and liquid intake and
      output will be monitored. Subjects are allocated at random (like tossing a coin) to receive
      Y242 or placebo (dummy). Safety, tolerability and pharmacokinetic data will be summarised and
      available results considered in deciding dose escalation, with stopping rules designed to
      enable us to explore the relationship between dose and adverse effect (eg nausea) without
      causing unacceptable nausea or other symptoms in the volunteers.
    

Intervention name(s): Y242; 0.9% saline
Intervention type(s): Drug; Drug
Intervention description(s): 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
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)
Primary purpose: Treatment
Keywords: Obesity; Peptide YY; Food intake; Safety; Pharmacokinetics