Clinical trial NCT01515319
Conditions: Obesity
Keywords: Obesity Peptide YY Food intake Safety Pharmacokinetics
Sponsor: Imperial College London
Start date: 2012-04-01; Completion date: 2013-02-01
Enrollment: 68 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief 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.

Arms: arm 1: Y242 single dose, subcutaneous arm 2: Y242 single dose, subcutaneous arm 3: Y242 single dose, subcutaneous arm 4: Y242 single dose, subcutaneous arm 5: Y242 single dose, subcutaneous arm 6: Y242 single dose, subcutaneous arm 7: 0.9% saline arm 8: Y242 single subcutaneous dose, administered once a week for 5 weeks arm 9: Y242 single subcutaneous dose, administered once a week for 5 weeks arm 10: 0.9% saline
Interventions: intervention 1: Y242 intervention 2: 0.9% saline
Intervention descriptions: intervention 1: 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) intervention 2: Identical volume to that of Y242

Protocol documents: