A First-Time-in-Human Study to Assess the Safety and Tolerability of PP 1420 in Healthy Subjects
Condition: Obesity
MeSH terms: Obesity
Study type: Interventional
Phase: Phase 1

Summary: 
      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 "Pancreatic
      Polypeptide" (PP). We have previously shown that injections of human PP reduces appetite and
      food intake. We have now developed a very similar chemical, PP 1420, as a treatment for
      obesity. PP 1420 has been tested in animals and has been shown to be safe, and to reduce
      their appetite. This study will test PP 1420 for its safety and tolerability in humans.
    

Detailed description: 
      More than 20 percent 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 are a couple of licensed medications 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 it can be risky and is 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. This study will assess the safety and
      tolerability of PP 1420 in humans, and is the first time humans have been given this
      medication.
    

Intervention name(s): PP 1420; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Single dose of PP 1420, administered subcutaneously at either 2mg, 4mg or 8mg.; 0.9% saline
Other intervention name(s): PP 1420 pancreatic polypeptide analog; Saline
Intervention MeSH terms: Pancreatic Polypeptide
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: There were three dosing periods. Each subject (n=12) was randomised to receive up to two doses of placebo and/or up to three ascending doses of PP 1420 dosed as s.c. injection. During each dosing period eight subjects received active drug and four received placebo. Subjects could also be randomised to receive one further dose of PP 1420 or placebo, if needed, to explore an intermediate dose based upon a review of safety, tolerability, and PK data from the previous cohorts.
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: obesity; pancreatic polypeptide; gut hormones