Study on Analgesia of GIC-1001 & GIC-1002 on Visceral Pain, Rectal Sensory Threshold Using the Barostat Method
Condition: Pain; Cancer; Colonic Disease
MeSH terms: Colonic Diseases; Visceral Pain
Study type: Interventional
Phase: Phase 1

Summary: 
      This study evaluates colonic analgesia by comparing two novel formulations, GIC-1001 and
      GIC-1002 with placebo using a barostat distender. The healthy male and female volunteers
      randomized to one of 5 possible treatments will be exposed to rectal distension following a
      3-day treatment TID. The barostat methodology is a well-established and validated way to
      assess visceral pain. Visceral pain will be evaluated during exposure to varying distender
      pressures using a visual analog scale.
    

Detailed description: 
      The objectives of this single center, randomized, double-blinded, placebo-controlled Phase I
      clinical study include the evaluation of visceral pain intensity under rectal distension
      following the oral administration of either of two doses of GIC-1001 or of either of two
      doses of GIC-1002, equimolar to the first formulation, or of placebo in 90 healthy subjects.

      The barostat intra-balloon pressure required to elicit pre-defined rectal sensory symptoms
      (i.e. first sensation, need to defecate, urgency to defecate and pain) will also be
      determined. Rectal sensory symptom ratings and rectal compliance under increased rectal
      distension will also be evaluated.

      The contribution of hydrogen sulphide (H2S) to the colonic analgesic activity of GIC-1001 by
      comparison to that of GIC-1002 will be evaluated following steady state pharmacokinetic
      analysis. To further comprehend the non-linear, U shape dose response curve observed with
      GIC-1001 in a previous Phase II a trial.

      Finally, the safety of GIC-1002 in healthy volunteers will also be evaluated.
    

Intervention name(s): GIC-1001 375 mg TID; GIC-1001 500 mg TID; GIC-1002 345 mg TID (equimolar to GIC-1001 375 mg TID); GIC-1002 460 mg (equimolar to GIC-1001 500 mg); Placebo
Intervention type(s): Drug; Drug; Drug; Drug; Other
Intervention description(s): GIC-1001 375 mg TID mid-dose, oral tablet, white-coated, to be taken with water; GIC-1001 500 mg TID high-dose, oral tablet, white-coated, to be taken with water; GIC-1002 345 mg TID mid-dose, oral tablet, white-coated, to be taken with water; GIC-1002 460 mg TID high-dose, oral tablet, white-coated, to be taken with water; Placebo identical and matching active drugs GIC-1001 and GIC-1001
Other intervention name(s): trimebutine 3-thiocarbamoylbenzenesulfonate , TB-905-02; trimebutine 3-thiocarbamoylbenzenesulfonate , TB-905-02; non-H2S releasing tosylate salt; non-H2S releasing tosylate salt; sugar -pill
Intervention MeSH terms: Trimebutine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: rectal distension; rectal compliance; visceral pain; pain intensity; barostat; distender; VAS (Visual Analog Scale); rectal sensory threshold; analgesia; trimebutine; pain management; peripheral; colon cancer; H2S (hydrogen sulfide)