Safety, Tolerability and Efficacy Study of PP1420 in HV — PP14201b1c  

Obesity Clinical Trial

Official title: A Double-Blind, Randomised, Placebo-Controlled Dose Escalation Study to Assess the Safety, Tolerability and Efficacy of Single and Multiple Doses of PP 1420 in Healthy Subjects.

Status Terminated

Clinical Trial Summary

Obesity is a growing pandemic which affects 1 in 4 adults in the UK, and shortens life by increasing cardiovascular disease, diabetes and cancer. Current treatments for obesity have either poor efficacy or significant side effects. Pancreatic polypeptide (PP) is a promising new drug target as it produces powerful appetite suppression which, following a 90-minute infusion continues to act for 24 h in man. We have developed a new long lasting high potency analogue of PP, PP1420. This is delivered as a once-a-day subcutaneous injection via a painless fine-gauge needle.

In a first-time-in-man Phase 1a trial, that PP 1420 proved safe, well tolerated, and had extended pharmacokinetics compared to PP itself.

We now plan to study the safety and PK of PP1420 up to 64mg. We will also assess:

1. Its efficacy in reducing food intake after a single dose in a Phase 1B study in healthy volunteers.

2. Its efficacy in reducing food intake and weight after multiple dosing in a Phase 1C study in healthy volunteers.

Clinical Trial Description

More than 25% of people in the UK are obese. People with obesity have a shorter life expectancy, and have a higher risk of having heart attacks, strokes, high blood pressure, diabetes, and certain cancers.

At the moment, there is no treatment for obesity that is both effective and safe. Advising people to change their diet and to exercise more is frequently ineffective, and any loss in weight seen is usually temporary. There is only one medications licensed for the purpose of losing weight, but they are limited by side-effects. Finally, gastric bypass and similar surgeries are effective at reducing weight permanently, but can be risky and restricted only to very motivated people.

"Gut hormones" are natural chemicals made by the bowels when you eat. They work to reduce appetite and hunger when you eat, so that you will eat enough for your needs. We think that one of the reasons why gastric bypass surgery is so effective is because the surgery causes an increase in gut hormone secretion into the bloodstream, which suppresses appetite. One of these hormones is pancreatic polypeptide (PP), which is released into the bloodstream by cells in the pancreas after eating. When human PP is given to healthy volunteers as an injection, we see that they have a reduced appetite and food intake with no side-effects such as feeling sick or vomiting.

Human PP does not last long in the blood stream. In order to make it into a new, safe and effective drug for obesity, we have developed a new form of PP, which is very similar but not identical to human PP, that we expect will last longer in the blood. We call this PP 1420.

In testing, PP 1420 reduced food intake in animals, and was safe in them at much higher doses than those we plan to give in the current study.

PP1420 has previously been give to healthy volunteers in single doses up to 8mg without any serious problems. All doses were well tolerated.

This study will examine the safety and tolerability of PP 1420 when given at single doses of higher doses, up to 64 mg, and the safety, tolerability and efficacy of PP 1420 when given in multiple doses for up to 28 days. ;

Related Conditions & MeSH terms

• Obesity

• NCT number: NCT02221765
• Study type: Interventional
• Source: Imperial College London
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: August 2014
• Completion date: May 2016