A Phase 2a, Proof-of-Concept Study of GIC-1001 in the Management of Visceral Pain During Sedation-Free, Full Colonoscopy
Condition: Pain; Cancer; Colonic Diseases
MeSH terms: Colonic Diseases; Visceral Pain
Intervention: GIC-1001
Intervention description: GIC-1001 oral tablet, white-coated, to be taken with water
Intervention MeSH terms: Trimebutine
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 308.0
Sex: All
Minimum age: 40 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: colonoscopy; sedation-free; colorectal cancer; CRC screening; prevention; analgesia; colonic; kappa; opioid agonist; pain management; oral; hydrogen sulfide; peripheral

Summary:

      GIC-1001 is a novel, orally-administered, colonic analgesic drug developed as an alternative
      to i.v. sedation during full colonoscopy. It will be evaluated for efficacy and safety in a
      multi-center, randomized, double-blind, placebo controlled, dose-ranging, proof of concept
      Phase 2a trial. Up to 240 patients will receive one of 3 doses of GIC-1001 or its matching
      placebo. A pharmacokinetic evaluation will be carried out on a subset of patients (N: 24).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Signed and dated written Informed Consent obtained.

          2. Males or females.

          3. Aged 40-75 years.

          4. Indication for full colonoscopy for colorectal cancer screening or investigation,
             including subjects presenting suggestive symptoms and who need a differential
             diagnosis.

          5. Colonoscopy naïve subjects, i.e. who never underwent colonoscopy before, will be
             eligible, as well as non-naïve subjects who have previously undergone unsedated
             colonoscopy , or who had sedated colonoscopy at least 10 years prior (i.e. ≥ 10 years)
             to enrolment

          6. Eligible for a procedure without sedation.

          7. Able to complete questionnaires and use a Visual Analog Scale (VAS), including
             sufficient English, French or Spanish speaking skills as well as adequate eyesight and
             hearing

          8. BMI ≥ 19, BMI ≤ 40 kg/m2.

        Exclusion Criteria:

          1. Known allergy or intolerance to trimebutine (Modulon® or generic).

          2. Known allergy or intolerance to sulfur-containing drugs (e.g. N-acetylcysteine or
             captopril).

          3. Previous gastrointestinal or gynecologic surgery, e.g. ileostomy, pelvic surgery,;
             however, patients with an appendectomy are eligible.Patients who have had a tubal
             ligation at least 10 years prior (i.e. ≥ 10 years) to enrolment are also eligible.

          4. Diagnosed Inflammatory Bowel Disease (IBD).

          5. Visceral hypersensitivity conditions such as Irritable Bowel Syndrome (IBS).

          6. Clinically significant renal and/or hepatic impairment.

          7. History of peritonitis.

          8. Known severe diverticular disease.

          9. Severe diverticulosis as documented by prior imaging series

         10. Known or suspected stenosis of the colon.

         11. Chronic pain syndrome such as fibromyalgia and endometriosis.

         12. Any clinically-relevant abnormality identified on the screening, history, physical
             examination, 12-lead ECG or laboratory examination, which would, in the Investigator's
             opinion, preclude the administration of investigational drug product, GIC1001

         13. Unexpected and significant visceral pain reported by subject prior to colonoscopy.

         14. Dementia.

         15. Diagnosed clinically significant psychiatric illness, including severe anxiety
             disorders that may affect the subject's perception of visceral pain or ability to
             participate in the study.

         16. Patient is a lactating female.

         17. Female is of childbearing potential sexually active who are unwilling or unable to use
             an acceptable method of contraception (which includes oral or implanted
             contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap, use of a
             condom by the sexual partner or sterile sexual partner) throughout the duration of the
             study and 1 month following study completion.

         18. Female is of childbearing potential, sexually abstinent who does not agree to continue
             abstinence or to use one of the acceptable methods of birth control should sexual
             activity commence.

         19. Any serious medical condition that could increase the risk of adverse reactions with
             trimebutine.

         20. Participation in another experimental drug trial within 30 days of randomization.