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A Phase 2a, Proof-of-Concept Study of GIC-1001 in the Management of Visceral Pain During Sedation-Free, Full Colonoscopy

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ClinicalTrials.gov Identifier: NCT01926444
Recruitment Status : Completed
First Posted : August 21, 2013
Results First Posted : May 8, 2019
Last Update Posted : May 8, 2019
Sponsor:
Collaborators:
JSS Medical Research Inc.
Algorithme Pharma Inc
Information provided by (Responsible Party):
gicare Pharma Inc.

Brief 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).

Condition or disease Intervention/treatment Phase
Pain Cancer Colonic Diseases Drug: GIC-1001 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 308 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Proof-of-Concept Study of GIC-1001 for the Management of Visceral Pain in Subjects Undergoing Sedation-Free, Full Colonoscopy
Study Start Date : July 2013
Actual Primary Completion Date : March 2014
Actual Study Completion Date : March 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Colonoscopy

Arm Intervention/treatment
Experimental: GIC-1001 low dose
GIC-1001 , 250 mg TID during 3 consecutive days + a last, 10th dose in the morning of Day 4 (colonoscopy day)
Drug: GIC-1001
GIC-1001 oral tablet, white-coated, to be taken with water
Other Names:
  • trimebutine 3-thiocarbamoylbenzenesulfonate
  • TB-905-02

Experimental: GIC-1001 mid-dose
GIC-1001 , 375 mg TID during 3 consecutive days + a 10th dose in the morning of day 4 (colonoscopy day)
Drug: GIC-1001
GIC-1001 oral tablet, white-coated, to be taken with water
Other Names:
  • trimebutine 3-thiocarbamoylbenzenesulfonate
  • TB-905-02

Experimental: GIC-1001 , high dose
GIC-1001 , 500 mg TID during 3 consecutive days + a 10th dose in the morning of day 4 (colonoscopy day)
Drug: GIC-1001
GIC-1001 oral tablet, white-coated, to be taken with water
Other Names:
  • trimebutine 3-thiocarbamoylbenzenesulfonate
  • TB-905-02

Placebo Comparator: GIC-1001 matching placebo
Placebo, TID during 3 consecutive days, + a 10 th dose in the morning of day 4 (colonoscopy day)
Drug: GIC-1001
GIC-1001 oral tablet, white-coated, to be taken with water
Other Names:
  • trimebutine 3-thiocarbamoylbenzenesulfonate
  • TB-905-02




Primary Outcome Measures :
  1. Measurements of Visceral Pain, Using a 100-mm Visual Analog Scale (VAS) [ Time Frame: Assessed at different anatomical locations: (1) before colonoscopy, (2) insertion of scope in anus, (3) at rectosigmoid flexure, (4) at splenic flexure, (5) at hepatic flexure, (6) at caecum, (7) at splenic flexure on way back, (8) after colonoscopy. ]
    The Primary Outcomes Measure was the pain VAS 100-mm AUC (0mm = no pain; 100mm = worst pain), constructed from serial pain VAS measurements performed during colonoscopy. At least 8 pain VAS measurements were made, and the length of the colonoscope inserted (or removed on the way out) was recorded at every measurement. The X-axis of the VAS versus anatomical locations was defined accordingly: each VAS value corresponded to a relative length of inserted colonoscope (d/2Lc) of the X axis, where d was the actual length of the inserted colonoscope and 2Lc represented twice the total length of the colon examined (Lc). Before scope insertion the X value equaled zero. Once the caecum was reached, the X value was 0.5. Upon complete removal of the endoscope, the X value was 1. This allowed standardization of colonic length between study subjects. Visceral pain AUC (mm) was calculated from all serial measurements, where the length of inserted colonoscope determined the VAS measurement's location


Secondary Outcome Measures :
  1. Time to Caecum [ Time Frame: From the time of introduction of the colonoscope, to removal of colonoscope. Range of duration of colonoscopy 5.00- 50.10 minutes. ]
    Time to Caecum is the time taken by the physician to reach the caecum with the colonoscope, from the insertion in the anus. Time to Caecum was measured during colonoscopy, for which total duration of colonoscopy ranged between a minimum of 5.00 and a maximum of 50.10 minutes.

  2. Colonoscopy Completion Rate (%) [ Time Frame: Number of patients during trial with a complete colonoscopy, where the scope has reached the caecum during the colonoscopy. Range of duration of colonoscopy 5.00- 50.10 minutes. ]
    Qualitative outcome: colonoscopy completion is defined as a procedure performed entirely, from initial anal insertion, reaching of caecum, and complete removal of the scope. Completion rate is then the number of patient (%) with a complete colonoscopy (up to the caecum) divided by the number of trial participants.

  3. Safety-Plasma Concentrations of Trimebutine and N-Desmethyl-Trimebutine [ Time Frame: Day 4 prior to colonoscopy. ]
    A pharmacokinetic (PK) analysis was carried out on the first 24 patients randomized, equally distributed between treatment groups; 18 patients were assigned to active treatment

  4. Total Examination Time (Colonoscopy) [ Time Frame: From the time of introduction of the colonoscope, to removal of colonoscope. Range of duration of colonoscopy 5.00- 50.10 minutes. ]
    Defined as the time from endoscope insertion to complete removal of the endoscope; measured in minutes

  5. Endoscopist's Perception of Colonoscopy- Adequacy of Analgesia, Difficulty of Insertion and Withdrawal [ Time Frame: From the time of introduction of the colonoscope, to removal of colonoscope. Range of duration of colonoscopy 5.00- 50.10 minutes. ]
    Endoscopist's perception of the adequacy of analgesia, difficulty of insertion and withdrawal measured on a five-point Likert scale: Strongly Agree, Agree, Agree nor Disagree, Disagree, Strongly Disagree

  6. Endoscopist's Perception of Colonoscopy- Amount of Colonic Spasm on Insertion and Withdrawal [ Time Frame: From the time of introduction of the colonoscope, to removal of colonoscope. Range of duration of colonoscopy 5.00- 50.10 minutes. ]
    Endoscopist's perception of the amount of colonic spasm on insertion and withdrawal measured on five-point Likert scale according to the following: Strongly Agree, Agree, Agree nor Disagree, Disagree, Strongly Disagree

  7. Patient's Willingness to Repeat Experience [ Time Frame: Post-colonoscopy- during subject recovery ]
    Patients' willingness for repeat colonoscopy, was assessed with the Patient Willingness to Repeat Experience (P.W.R.E.) questionnaire (1 question), asking patients to rate their willingness to repeat the procedure according to a 5-point Likert scale: Strongly Agree, Agree, Agree nor Disagree, Disagree, Strongly Disagree. The P.W.R.E was administered after the colonoscopy during subject recovery.

  8. Subject Satisfaction and Acceptability of the Colonic Analgesia - Patient's Global Impression of Abdominal Pain [ Time Frame: Post-colonoscopy- during subject recovery ]
    Subject satisfaction and acceptability of the colonic analgesia modality offered by GIC-1001 was assessed with the Patient Global Impression of Abdominal Pain (P.G.I.A.P.) (1 question), asking patients to rate their pain during the procedure according to a 5-point Likert scale: Absent, Mild, Moderate, Severe, Intolerable. The P.G.I.A.P was administered after the colonoscopy during subject recovery.



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Ages Eligible for Study:   40 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01926444


Locations
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United States, Arizona
Mayo Clinic
Scottsdale, Arizona, United States, 85259
United States, California
Anaheim Clinical Trials
Anaheim, California, United States, 92801
Precision Research Institute
Chula Vista, California, United States, 91910
Precision Research Institute
San Diego, California, United States, 92114
United States, Florida
Avail Clinical Research LLC
DeLand, Florida, United States, 32720
The Center for GI Disorders
Hollywood, Florida, United States, 33021
United States, Maryland
Mid-Atlantic Medical Research Centers
Hollywood, Maryland, United States, 20636
United States, Minnesota
Mayo Clinic Rochester
Rochester, Minnesota, United States, 55910
United States, New Jersey
PharmaTrials
Hillsborough, New Jersey, United States, 08844
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
United States, South Carolina
Gastroenterology Associates of Orangeburg
Orangeburg, South Carolina, United States, 29118
Canada, British Columbia
GIRI (GI Research Institute)
Vancouver, British Columbia, Canada, V6Z 2K5
Canada, Ontario
Toronto Digestive Disease Associates
Toronto, Ontario, Canada, L4L4Y7
Canada, Quebec
Clinique 1037
Montreal, Quebec, Canada, H2X3H9
Spécialistes MD Specialists
Montreal, Quebec, Canada, H3Z 2P9
Sponsors and Collaborators
gicare Pharma Inc.
JSS Medical Research Inc.
Algorithme Pharma Inc
Investigators
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Study Chair: Mark V Larson, MD Mayo Clinic, Rochester, MN, USA
Principal Investigator: Michael DeMicco, MD Anaheim Clinical Trials, Anaheim, CA, USA
Principal Investigator: Mark Lamet, MD The Center of GI Disorders, Hollwood, FL, USA
Principal Investigator: Taddese Desta, MD Precision Research Institute, San Diego, CA, USA
Principal Investigator: Cynthia Schaeffer, MD Precision Research Institute, Chula Vista, CA, USA
Principal Investigator: Vivek Gumaste, MD Montefiore Medical Center, NY, USA
Principal Investigator: Theadore Ptak, MD Toronto Digestive Disease Associates, Toronto, ON, Canada
Principal Investigator: Anand Sahai, MD Clinique 1037, Montreal, QC, Canada
Principal Investigator: Umedchandra Shah, MD Mid-Atlantic Medical Research Centers, Hollyword, MD, USA
Principal Investigator: Suryakanth R. Gurudu, MD Mayo Clinical, Scottsdale Arizona
Principal Investigator: Robert Enns, MD GIRI (GI Research Institute), Vancouver, Canada
Principal Investigator: Narayanachar S Murali, MD Gastroenterology Associates of Orangeburg, SC, USA
Principal Investigator: Vishal Gupta, MD Avail Clinical Research LLC
Principal Investigator: Albert Cohen, MD Spécialistes MD Specialists
Principal Investigator: Vitaly Fishbein, MD PharmaTrials
Study Director: Dennis Riff, MD Anaheim Clinical Trials

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Responsible Party: gicare Pharma Inc.
ClinicalTrials.gov Identifier: NCT01926444     History of Changes
Other Study ID Numbers: GIC13-01
First Posted: August 21, 2013    Key Record Dates
Results First Posted: May 8, 2019
Last Update Posted: May 8, 2019
Last Verified: May 2019

Keywords provided by gicare Pharma Inc.:
colonoscopy
sedation-free
colorectal cancer
CRC screening
prevention
analgesia
colonic
kappa
opioid agonist
pain management
oral
hydrogen sulfide
peripheral

Additional relevant MeSH terms:
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Colonic Diseases
Visceral Pain
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Nociceptive Pain
Pain
Neurologic Manifestations
Signs and Symptoms