Dr Eric Sicard
Algorithme Pharma Inc.
1200 Beaumont Ave
+1 514 858 6077
A double-blind, placebo controlled, phase I study to assess safety, tolerability and pharmacokinetics of single and multiple ascending oral doses of GIC-1001 in normal healthy volunteers
GIC-1001 is a non-centrally-acting, orally-administered, hydrogen sulfide releasing opioid agonist, which intends to provide adequate colonic analgesia to patients undergoing sedation-free colonoscopy.
Please note that as of 11/03/2013, the anticipated end date for this trial was updated from 31/05/2013 to 08/03/2013.
Institutional Board Review Services, 09 November 2012 ref: IBRS-GIC-1001-09-NOV-2012
Randomized controlled phase I trial
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Gastroenterology / pain management / management of visceral pain during sedation-free colonoscopy
Experimental: GIC-1001 oral tablets
GIC-1001; 125 mg oral tablets; Single ascending doses (SAD) from 125 mg to 1000 mg; multiple ascending dose (MAD) from 125 mg to 500 mg TID over 7 successive days
Part 1: Single Doses Cohort A: Single dose of 125 mg of GIC-1001 or placebo; Cohort B: Single dose of 250 mg of GIC-1001 or placebo; Cohort C: Single dose of 375 mg of GIC-1001 or placebo; Cohort D: Single dose of 500 mg of GIC-1001 or placebo; and Cohort E: Single dose of 1000 mg of GIC-1001 or placebo. Up to 21 blood samples will be obtained over a 36 hour period.
Part 2: Multiple Doses, three times a day (TID) during 7 consecutive days; Cohort F: Multiple doses of 125 mg of GIC-1001 or placebo; Cohort G: Multiple doses of 250 mg of GIC-1001 or placebo; Cohort H: Multiple doses of 375 mg of GIC-1001 or placebo; and Cohort I: Multiple doses of 500 mg of GIC-1001 or placebo. Up to 18 blood samples will be obtained over a 7 day period.
Part 3: one single dose of GIC-1001 to be selected for the Food Effect cross-over evaluation. A total of 16 blood samples will be obtained over a 36 hour period.
Placebo Comparator: GIC-1001 matching placebo
Matching placebo, single or multiple dosing
Physical exams, 24 hour cardiac monitoring, and a complete battery of biochemical and hematological lab tests will be done to assess the safety and tolerability of GIC-1001 in all dosing cohorts.
Primary outcome measures
Safety and Tolerability: Single and multiple (7 consecutive days) doses
In this Phase I study, 5 single ascending doses of GIC-1001 will be studied, as well as 4 multiple doses administered during 7 consecutive days ( TID regimen). As well, one single dose will be administered with and without food to assess the effect of food intake on the PK of the study drug. Safety issues monitored.
Secondary outcome measures
Pharmacokinetics: Up to 36 hours for single ascending doses; every day and up to 8 hour post last dose for multiple ascending doses
Blood samples will be obtained over a 36 hour period in the single dose portion of the study and over 7 days, every morning prior to GIC-1001, as well as 8 hours post-last dose in the multiple dosing phase. Main absorption and disposition parameters using a non-compartmental approach will be measured.
For GIC-1001 and its metabolites, the pharmacokinetic parameters of interest for the single dose regimens will be Cmax, AUC0-8, AUCT, AUC∞, Tmax, AUCT/∞, Kel, T½el, Cl/F and Vd/F. The parameters Cmax, AUC0-8, AUCT and AUC∞ will be dose-normalized, and their natural logarithm will be calculated. The pharmacokinetic parameters of interest for the multiple dose regimens will be Cmax, Tmax, AUCτ, Cmin, Cpds, Fluctuation and Swing. The parameters Cmax, AUCτ and Cmin will be dose-normalized, and the natural logarithm of Cmax, AUCτ, Cmin and Cpds of will be calculated. For hydrogen sulfide and thiosulfate, the pharmacokinetic parameters of interest will be Cmax, Tmax and AUC0-4.
Overall trial start date
Overall trial end date
Participant inclusion criteria
1. Male or female volunteer
2. A female volunteer must meet one of the following criteria:
2.1. Participant is of childbearing potential and agrees to use one of the accepted contraceptive regimens from the screening visit until 2 months after the last drug administration. Additionally, if the participant is using systemic contraceptives, she must use an additional form of acceptable contraception from first drug administration until 2 months after the last drug administration. OR
2.2. Participant is of non-childbearing potential, defined as a female who had had a hysterectomy or tubal ligation, is clinically considered infertile or is in a menopausal state (at least 1 year without menses)
3. A male volunteer with sexual partners who are pregnant, possibly pregnant, or who could become pregnant must meet the following criterion: Participant agrees to use one of the accepted contraceptive regimens from first drug administration until 3 months after the last drug administration. An acceptable method of contraception includes one of the following: Abstinence from heterosexual intercourse or condom with spermicide
4. Volunteer aged of at least 18 years but not older than 50 years
5. Volunteer with a body mass index (BMI) greater than or equal to 18.50 and below 30 kg/m2
6. Non- or ex-smokers. An ex-smoker is defined as someone who completely stopped smoking for at least 6 months before day 1 of this study
7. Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without any clinical significance
8. Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on physical examination and/or clinical laboratory evaluations (hematology, biochemistry, ECG and urinalysis)
Target number of participants
Participant exclusion criteria
1. History of significant hypersensitivity to trimebutine, to sulfur containing drugs (e.g. Captopril) or any related products (including excipients of the formulation) as well as severe hypersensitivity reactions (like angioedema) to any drugs
2. Presence of significant gastrointestinal, liver/kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects
3. History of significant gastrointestinal, liver or kidney disease that may affect drug bioavailability
4. Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease
5. Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases
6. Presence of out-of-range cardiac interval (PR < 110 msec, PR > 200 msec, QRS <60 msec, QRS >110 msec and QTc > 440 msec) on the screening ECG or other clinically significant ECG abnormalities
7. Known presence of rare hereditary problems of galactose and /or lactose intolerance
8. Use of cysteine, methionine, and other sulfur containing amino acid supplements in the previous 7 days before day 1 of this study
9. Maintenance therapy with any drug, or significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
10. Any clinically significant illness in the previous 28 days before day 1 of this study
11. Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin and St John's Wort), in the previous 28 days before day 1 of this study
12. Any history of tuberculosis and/or prophylaxis for tuberculosis
13. Positive urine screening of ethanol and/or drugs of abuse
14. Positive results to HIV, HBsAg or anti-HCV tests
15. Females who are pregnant according to a positive serum pregnancy test
16. Volunteers who took an Investigational Product (in another clinical trial) or donated 50 mL or more of blood in the previous 28 days before day 1 of this study
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Algorithme Pharma Inc.
gIcare Pharma Inc (Canada)
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting