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

NCT01926444 | Completed Phase 2 Results DMC

• 1 other identifier: GIC13-01
• Study Type: interventional
• Target: 308
• Locations: 2 countries
• Sites: 15

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).

Conditions

Pain; Cancer; Colonic Diseases

Keywords

colonoscopy; sedation-free; colorectal cancer; CRC screening; prevention; analgesia; colonic; kappa; opioid agonist; pain management; oral; hydrogen sulfide; peripheral

Outcome Measures

Primary Outcomes (1)

• Measurements of Visceral Pain, Using a 100-mm Visual Analog Scale (VAS)

  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

  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.

Secondary Outcomes (8)

• Time to Caecum

  From the time of introduction of the colonoscope, to removal of colonoscope. Range of duration of colonoscopy 5.00- 50.10 minutes.

• Colonoscopy Completion Rate (%)

  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.

• Safety-Plasma Concentrations of Trimebutine and N-Desmethyl-Trimebutine

  Day 4 prior to colonoscopy.

• Total Examination Time (Colonoscopy)

  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 Colonoscopy- Adequacy of Analgesia, Difficulty of Insertion and Withdrawal

  From the time of introduction of the colonoscope, to removal of colonoscope. Range of duration of colonoscopy 5.00- 50.10 minutes.

Study Arms (4)

GIC-1001 low dose

EXPERIMENTAL

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 mid-dose

EXPERIMENTAL

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 , high dose

EXPERIMENTAL

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 matching placebo

PLACEBO COMPARATOR

Placebo, TID during 3 consecutive days, + a 10 th dose in the morning of day 4 (colonoscopy day)

Drug: GIC-1001

Interventions

GIC-1001 DRUG

GIC-1001 oral tablet, white-coated, to be taken with water

Also known as: trimebutine 3-thiocarbamoylbenzenesulfonate, TB-905-02

GIC-1001 , high dose; GIC-1001 low dose; GIC-1001 matching placebo; GIC-1001 mid-dose

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated written Informed Consent obtained.
• Males or females.
• Aged 40-75 years.
• Indication for full colonoscopy for colorectal cancer screening or investigation, including subjects presenting suggestive symptoms and who need a differential diagnosis.
• 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
• Eligible for a procedure without sedation.
• 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
• BMI ≥ 19, BMI ≤ 40 kg/m2.

You may not qualify if:

• Known allergy or intolerance to trimebutine (Modulon® or generic).
• Known allergy or intolerance to sulfur-containing drugs (e.g. N-acetylcysteine or captopril).
• 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.
• Diagnosed Inflammatory Bowel Disease (IBD).
• Visceral hypersensitivity conditions such as Irritable Bowel Syndrome (IBS).
• Clinically significant renal and/or hepatic impairment.
• History of peritonitis.
• Known severe diverticular disease.
• Severe diverticulosis as documented by prior imaging series
• Known or suspected stenosis of the colon.
• Chronic pain syndrome such as fibromyalgia and endometriosis.
• 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
• Unexpected and significant visceral pain reported by subject prior to colonoscopy.
• Dementia.
• 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.

Sponsors & Collaborators

• gicare Pharma Inc.: lead
• JSS Medical Research Inc.: collaborator
• Algorithme Pharma Inc: collaborator

Study Sites (15)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

Anaheim Clinical Trials

Anaheim, California, 92801, United States

Location

Precision Research Institute

Chula Vista, California, 91910, United States

Location

Precision Research Institute

San Diego, California, 92114, United States

Location

Avail Clinical Research LLC

DeLand, Florida, 32720, United States

Location

The Center for GI Disorders

Hollywood, Florida, 33021, United States

Location

Mid-Atlantic Medical Research Centers

Hollywood, Maryland, 20636, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55910, United States

Location

PharmaTrials

Hillsborough, New Jersey, 08844, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Gastroenterology Associates of Orangeburg

Orangeburg, South Carolina, 29118, United States

Location

GIRI (GI Research Institute)

Vancouver, British Columbia, V6Z 2K5, Canada

Location

Toronto Digestive Disease Associates

Toronto, Ontario, L4L4Y7, Canada

Location

Clinique 1037

Montreal, Quebec, H2X3H9, Canada

Location

Spécialistes MD Specialists

Montreal, Quebec, H3Z 2P9, Canada

Location

MeSH Terms

Conditions

Pain; Neoplasms; Colonic Diseases; Colorectal Neoplasms; Agnosia

Interventions

trimebutine 3-thiocarbamoylbenzenesulfonate

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Rectal Diseases; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases

Results Point of Contact

• Title: Patrick Colin
• Organization: PCC INC.

PCOLIN@VIDEOTRON.CA

514-586 9297

Study Officials

• Mark V Larson, MD

  Mayo Clinic, Rochester, MN, USA

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

• Dennis Riff, MD

  Anaheim Clinical Trials

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2013
• First Posted: August 21, 2013
• Study Start: July 1, 2013
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: May 8, 2019
• Results First Posted: May 8, 2019

Record last verified: 2019-05

Locations

CA (4); US (11)