A clinical phase I study on GIC-1001 in healthy volunteers
| ISRCTN | ISRCTN09480239 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN09480239 |
| ClinicalTrials.gov number | NCT01738425 |
| Secondary identifying numbers | GIC-P2-458 |
- Submission date
- 26/11/2012
- Registration date
- 11/12/2012
- Last edited
- 26/04/2017
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Background and study aims
GIC-1001 is a drug that is intended to provide analgesia (pain relief) for patients undergoing colonoscopy, where a thin flexible tube with a tiny camera on the end (colonoscope) is used to look inside the bowel. It may later be used for pain management in colonic diseases such as irritable bowel syndrome and ulcerative colitis. The aim of this study is to assess the safety, tolerability (side effects) and pharmacokinetic profile (movement of the drug into, through, and out of the body) of GIC-1001 in healthy volunteers.
Who can participate?
Healthy volunteers aged 18 to 50
What does the study involve?
In Part 1 participants are randomly allocated to take GIC-1001 tablets at one of five doses or placebo (dummy) tablets once a day for 7 days. Up to 21 blood samples are taken over a 36-hour period. In Part 2 participants are randomly allocated to take GIC-1001 tablets at one of four doses or placebo (dummy) tablets three times a day for 7 days. Up to 18 blood samples are taken over a 7-day period. In Part 3 participants take a single dose of GIC-1001 in two periods with and without food to assess the effects of food intake on GIC-1001. A total of 16 blood samples are taken over a 36-hour period. Physical examinations, 24-hour cardiac (heart) monitoring and lab tests are carried out to assess the safety and tolerability of GIC-1001 in all groups.
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
Algorithme Pharma (Canada)
When is the study starting and how long is it expected to run for?
November 2012 to March 2013
Who is funding the study?
gIcare Pharma Inc (Canada)
Who is the main contact?
Dr Patrick Colin
pcolin@gicarepharma.com
Contact information
Dr Eric Sicard
Scientific
Scientific
Algorithme Pharma Inc.
1200 Beaumont Ave
Montreal
H7V 4B3
Canada
| Phone | +1 (0)514 858 6077 |
|---|---|
| esicard@algopharm.com |
Study information
| Study design | Randomized controlled phase I trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | 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 |
| Study acronym | GIC-1001 |
| Study objectives | 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. |
| Ethics approval(s) | Institutional Board Review Services, 09/11/2012, ref: IBRS-GIC-1001-09-NOV-2012 |
| Health condition(s) or problem(s) studied | Gastroenterology/pain management/management of visceral pain during sedation-free colonoscopy |
| Intervention | 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. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | GIC-1001 |
| Primary outcome measure | 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 study start date | 14/11/2012 |
| Completion date | 08/03/2013 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 80 |
| Key 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) |
| Key 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 |
| Date of first enrolment | 14/11/2012 |
| Date of final enrolment | 08/03/2013 |
Locations
Countries of recruitment
- Canada
Study participating centre
Algorithme Pharma Inc.
Montreal
H7V 4B3
Canada
H7V 4B3
Canada
Sponsor information
gIcare Pharma Inc (Canada)
Industry
Industry
c/o Dr Patrick Colin
2202 Av Oxford
Montreal
H4A 2X8
Canada
| Phone | +1 (0)514 586 9297 |
|---|---|
| pcolin@gicarepharma.com | |
| Website | http://www.gicarepharma.com |
Funders
Funder type
Industry
gIcare Pharma Inc (Canada)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/11/2014 | Yes | No |
Editorial Notes
26/04/2017: Plain English summary and publication reference added.
11/03/2013: The overall trial end date was changed from 31/05/2013 to 08/03/2013.
