Study on Analgesia of GIC-1001 & GIC-1002 on Visceral Pain, Rectal Sensory Threshold Using the Barostat Method

NCT02276768 | Completed Phase 1

• 2 other identifiers: GIC1.14.1.02GCR-P7-403
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pain; Cancer; Colonic Disease

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)

Outcome Measures

Primary Outcomes (1)

• Mean visceral pain intensity score following dosing with GIC-1001 375 mg TID

  Mean visceral pain intensity score in millimeters (mm) on a 100-mm Visual Analog Scale (VAS) based on 7 measurements collected at increasing rectal distension pressures from 24 to 60 mmHg following the oral administration of the GIC-1001 375 mg TID x 3 days regimen, and comparing it to placebo.

  Stage IV, test lasts approximately 20 min.VAS scores collected every 2 minutes at a colorectal distension pressures 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60 mmHg in random order, each maintained for 1 minute.A 1-minute resting period follows between.

Secondary Outcomes (13)

• Mean visceral pain intensity score following dosing with GIC-1001 500 mg TID

  Stage IV, test lasts approx. 20 min.VAS scores collected every 2 min. at colorectal distension pressures 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60 mmHg in random order, each maintained for 1 minute. A 1-minute resting period follows VAS scoring..

• Mean visceral pain intensity score following dosing with GIC-1002 345 mg TID and GIC-1002 460 mg TID

  Stage IV, test lasts approx. 20 min.VAS scores collected every 2 min. at colorectal distension pressures 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60 mmHg in random order, each maintained for 1 minute. A 1-minute resting period follows VAS scoring.

• Barostat pressure required to elicit pre-defined rectal sensory symptoms

  Stage III lasts about 15 min.VAS scores collected every 1 minute at increasing colorectal distension pressures: 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56 and 60 mmHg. Each pressure is held for 1 minute for VAS score report. No resting period.

• Rectal sensory intensity score

  Stage III lasts about 15 min.Intensity score recorded every minute at te same time as VAS for rectal sensory compliance...

• Rectal compliance under increasing rectal distension

  Stage III lasts about 15 min. Overall rectal compliance is calculated over a 15-minute period with pressure increasing sequentially from 4 to 60 mmHg.

Study Arms (5)

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 375 mg TID

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 500 mg TID

GIC-1002 mid-dose

ACTIVE COMPARATOR

GIC-1002 345 mg TID (equimolar to GIC-1001 375 mg) 345 mg TID during 3 consecutive days + a 10th dose in the morning of day 4 (colonoscopy day)

Drug: GIC-1002 345 mg TID (equimolar to GIC-1001 375 mg TID)

GIC-1002 high-dose

ACTIVE COMPARATOR

GIC-1002 460 mg (equimolar to GIC-1001 500 mg) 460 mg TID during 3 consecutive days + a 10th dose in the morning of day 4 (colonoscopy day)

Drug: GIC-1002 460 mg (equimolar to GIC-1001 500 mg)

Placebo matching GIC-1001 and GIC-1002

PLACEBO COMPARATOR

Placebo matching GIC-1001 doses Placebo matching GIC-1002 doses Placebo, TID during 3 consecutive days, + a 10 th dose in the morning of day 4 (colonoscopy day)

Other: Placebo

Interventions

GIC-1001 375 mg TID DRUG

GIC-1001 375 mg TID mid-dose, oral tablet, white-coated, to be taken with water

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

GIC-1001 mid-dose

GIC-1001 500 mg TID DRUG

GIC-1001 500 mg TID high-dose, oral tablet, white-coated, to be taken with water

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

GIC-1001 high-dose

GIC-1002 345 mg TID (equimolar to GIC-1001 375 mg TID) DRUG

GIC-1002 345 mg TID mid-dose, oral tablet, white-coated, to be taken with water

Also known as: non-H2S releasing tosylate salt

GIC-1002 mid-dose

GIC-1002 460 mg (equimolar to GIC-1001 500 mg) DRUG

GIC-1002 460 mg TID high-dose, oral tablet, white-coated, to be taken with water

Also known as: non-H2S releasing tosylate salt

GIC-1002 high-dose

Placebo OTHER

Placebo identical and matching active drugs GIC-1001 and GIC-1001

Also known as: sugar -pill

Placebo matching GIC-1001 and GIC-1002

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female volunteer
• A female volunteer must meet one of the following criteria:
• Participant is of childbearing potential and agrees to use one of the accepted contraceptive regimens from at least 28 days prior to the first dosing, during the study and for at least 30 days after the last dosing or participant is of non-childbearing potential, i.e. surgically sterile or menopausal (at least 1 year without menses)
• Age between 18 to 65 years
• kg/m2 ≥ Body Mass Index ≤ 18.50 kg/m2
• Light-, non- or ex-smokers. A light smoker is smoking 2 cigarettes or less per day for at least 3 months before Day 1. An ex-smoker is someone who completely stopped smoking for at least 6 months before Day 1
• Barostat naive or no barostat experience in the year preceding screening
• Clinical laboratory values within the laboratory's stated normal range; or without any clinical significance
• Have no history of clinically significant diseases or evidence of clinically significant findings on physical exam and/or clinical laboratory tests
• Have a normal anorectal area, confirmed by entry digital rectal exam (DRE) and
• Signed dated informed consent form by subject

You may not qualify if:

• Pregnant or lactating females
• History of significant hypersensitivity to trimebutine, to sulfur-containing drugs or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
• Presence of significant gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose undesired effects
• Diagnosis of Inflammatory Bowel Disease or Irritable Bowel Syndrome
• Criteria for functional bowel disorder (i.e. functional constipation, functional diarrhea and IBS) or abdominal pain, as reported by questionnaire
• Known history of rectosigmoid disease
• Abnormal anorectal findings during entry DRE
• History of abdominal surgery (except appendectomy or cholecystectomy)
• History of gastrointestinal obstruction, any rectal or colon surgery
• Known presence of piles or fissures, peri-anal pathology or any other rectal abnormalities
• Female subjects with history of gynecological surgery (˂ 10 years prior to screening or 1 year for tubal ligation or hysterectomy)
• Known history of, or risk factors for pelvic floor injury
• History of significant gastrointestinal, liver or kidney disease, or surgery
• Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease
• Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases

Sponsors & Collaborators

• gicare Pharma Inc.: lead
• Algorithme Pharma Inc: collaborator

Study Sites (1)

Algorithme Pharma Inc.

Montreal, Quebec, H3P-3P1, Canada

Location

MeSH Terms

Conditions

Pain; Neoplasms; Colonic Diseases; Visceral Pain; Agnosia; Colonic Neoplasms

Interventions

trimebutine 3-thiocarbamoylbenzenesulfonate

Condition Hierarchy (Ancestors)

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

Study Officials

• Eric Sicard, M.D.

  Algorithme Pharma Inc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2014
• First Posted: October 28, 2014
• Study Start: October 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: August 10, 2016

Record last verified: 2016-08

Locations

CA (1)