A First-Time-in-Human Study to Assess the Safety and Tolerability of PP 1420 in Healthy Subjects
Condition: Obesity
MeSH terms: Obesity
Intervention: PP 1420; Placebo
Intervention description: Single dose of PP 1420, administered subcutaneously at either 2mg, 4mg or 8mg.; 0.9% saline
Intervention MeSH terms: Pancreatic Polypeptide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
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)
Masking description: This was a double-blind study
Enrollment: 13.0
Sex: Male
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: obesity; pancreatic polypeptide; gut hormones

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy male as determined by a responsible physician, based on a medical evaluation
             including history, physical examination, vital signs, laboratory tests and 12-lead
             ECG.

          -  Between 18 and 50 years of age, inclusive, at the time of signing and dating the
             informed consent form.

          -  Body weight ≥70 kg and body mass index (BMI) within the range 18 - 35 kg/m2
             (inclusive).

          -  Capable of giving written informed consent, which includes compliance with the
             requirements and restrictions listed in the consent form.

          -  Willing and able to comply with the protocol for the duration of the study.

        Exclusion Criteria:

          -  As a result of the medical interview, physical examination, or screening
             investigations, the Investigator considers the subject unsuitable for the study.

          -  The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that
             will be screened for include amphetamines, barbiturates, cocaine, opiates,
             cannabinoids and benzodiazepines.

          -  A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
             result within 3 months of screening.

          -  A positive test for human immunodeficiency virus (HIV) antibody.

          -  History of migraine.

          -  History or evidence of abnormal eating behaviour, as observed through the Dutch Eating
             Behaviour (DEBQ) and SCOFF questionnaires.

          -  History of excessive alcohol consumption within 6 months of the study defined as an
             average weekly intake of greater than 21 units or an average daily intake of greater
             than 3 units. One unit is equivalent to 8 g of alcohol, a half-pint (approximately 240
             mL) of beer or 1 measure (25 mL) of spirits or 1 glass (125 mL) of wine.

          -  Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or
             nicotine-containing products within 6 months prior to screening.

          -  Has QTc at screening >450 msec.

          -  Systolic blood pressure outside the range 85 - 160 mmHg, diastolic blood pressure
             outside the range 45 - 100 mmHg, and/or heart rate outside the range 40 - 110 bpm.

          -  The subject has participated in a clinical trial and has received an investigational
             product within the following time period prior to the dosing day in the current study:
             90 days, five half-lives or twice the duration of the biological effect of the
             investigational product (whichever is longer).

          -  Exposure to more than four new chemical entities within 12 months prior to the first
             dosing day.

          -  Use of prescription or non-prescription drugs, including vitamins, herbal and dietary
             supplements within 14 days or five half-lives (whichever is longer) prior to the dose
             of study medication, which, in the opinion of the Investigator, may interfere with the
             study procedures or compromise subject safety.

          -  History of sensitivity to any of the study medications, or components thereof or a
             history of drug or other allergy that, in the opinion of the Investigator,
             contraindicates their participation.

          -  Where participation in the study would result in donation of blood in excess of 500 mL
             within 3 months before or after the study.

          -  Unwilling to abstain from consumption of caffeine- or xanthine- containing products
             for 24 hours prior to dosing until the post-dose assessment at each treatment level.

          -  Unwilling to abstain from use of illicit drugs.

          -  Unwilling to abstain from alcohol for 48 hours prior to dosing until final post-dose
             assessment at each treatment level.

          -  Unwilling to abstain from smoking or otherwise consuming tobacco for 24 hours prior to
             dosing until the post-dose assessment at each treatment level.

          -  Unwilling to use a condom during sexual activity from first dose until the end of the
             study.

          -  Vegans and subjects with milk or wheat intolerance or allergy as reported by the
             subject.

          -  Unwillingness or inability to follow the procedures outlined in the protocol.