Investigation of Efficacy and Safety of PPC-5650 to Experimental Induced Sensation and Pain in the Rectosigmoid
Condition: Pain
Study type: Interventional
Phase: Phase 1

Summary: 
      Irritable Bowel Syndrome (IBS) is a gastrointestinal disorder characterized by chronic
      abdominal pain and altered bowel habits in the absence of any organic cause. Patients with
      IBS visit the doctor more frequently, use more diagnostic tests, consume more medications,
      miss more workdays, and consume more overall direct costs than patients without IBS. More
      specific treatment of the localized symptoms of IBS is therefore needed, why the present
      study will investigate the effect and mechanisms of PPC-5650. PPC-5650 is a new chemical
      entity that can negatively modulate the activity of Acid sensing ion channels (ASICs). It is
      a potent low molecular weight inhibitor for this class of ion channels described to date.

      It is hypothesized that safety, efficacy and mechanisms of local administration in the rectum
      of PPC-5650 can be evaluated by use of experimental induced sensation and pain in the rectum.
    

Detailed description: 
      Clinical pain and especially visceral pain is diffuse and widespread, and normally associated
      with many autonomic symptoms that may blur the characterization of disease in clinical
      practice. When treating clinical pain analgesic effects are difficult to evaluate due to a
      number of factors other than the pain intensity. These modifiers of the effect may include
      complaints relating to psychological, cognitive and social aspects of the illness, as well as
      systemic reactions. Hence, any change in these factors will invariably also interfere with
      pain intensity and pain quality and bias the assessment of analgesics in clinical trials.

      Because of the confounders mentioned above, experimental pain models are often advantageous
      for characterizing analgesics. Basic mechanisms in pain perception, transduction and central
      processing can also be explored by means of human experimental pain models. These models,
      when applied to healthy volunteers or to patients, provide an important translational link
      between preclinical animal testing and human clinical trials. In clear contrast to clinical
      pain, experimental pain models allow the possibility of controlling the duration, the
      intensity and the nature of the pain stimulus. As pain is a multidimensional perception it is
      obvious that the reaction to a single stimulus of a certain modality only represents a
      limited part of the pain experience and therefore a variety of stimulus modalities are
      required to mimic the clinical situation. By use of a multi-modal pain model it is possible
      to induce sensation and pain in the rectum, investigating safety, effect and mechanisms of
      drugs.

      This is an exploratory study investigating effect, mechanisms and safety of PPC-5650 to
      experimental induced pain in patients with IBS. The study aims to provide data to support
      further evaluation of PPC-5650 in the gastrointestinal area.
    

Intervention name(s): PPC-5650; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Solution for administration in the rectum Single dose of 25µg/ml at a volume of 50ml; Solution for administration in the rectum Identical tp active solution but without active drug
Other intervention name(s): No other name; No other name
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Experimental pain; IBS; Rectum