A Clinical Phase I Study on GIC-1001 in Healthy Volunteers
|Colonic Diseases||Drug: GIC-1001; 125 mg oral tablets Drug: GIC-1001 matching placebo||Phase 1|
|Study Design:||Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official 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|
- Change in physical status [ Time Frame: 8 hours post- drug administration ]Safety and Tolerability Monitoring: changes from baseline in blood pressure, pulse rate, oxygen saturation of blood, and body temperature will be measured at 8 hours post drug administration.
- Pharmacokinetics [ Time Frame: 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.
- Change in ECG recording [ Time Frame: 3 hours post drug administration ]Safety and Tolerability Monitoring: In all cohorts, change from baseline of 12-lead ECG will be measured at 3 hours post-drug administration.
- Cardiac monitoring [ Time Frame: 23 hours post drug administration ]
Safety and Tolerability Monitoring: During Single Ascending Dosing only, continuous cardiac monitoring will be performed from approximately 1 hour prior to drug administration until at least 23 hours post-dose.
In cases where the alarm activation of the monitoring system takes place for notification of concerns and/or rhythm changes, a rhythm strip will be printed and filed as source data. These occurrences will be followed up through further medical investigation, and/or filing of AEs.
Any interruption of the patient monitoring due to clinical activities or else will be documented.
|Study Start Date:||November 2012|
|Study Completion Date:||May 2013|
|Primary Completion Date:||April 2013 (Final data collection date for primary outcome measure)|
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
Drug: GIC-1001; 125 mg oral tablets
Single ascending doses (SAD) from 125 mg to 1000 mg;
Multiple ascending doses from 125 mg to 500 mg, TID over 7 successive days
Other Name: hydrogen sulfide releasing opioid agonist
Placebo Comparator: GIC-1001 matching placebo
Matching placebo, single or multiple dosing
Drug: GIC-1001 matching placebo
Single ascending doses (SAD) [equivalent to active arm, 125 mg to 1000 mg]
Multiple ascending doses, TID over 7 successive days [equivalent to the active arm, 125 mg to 500 mg]
Other Name: Same tablet-based excipients, without GIC-1001 (active)
Each cohort of enrolled healthy volunteers will include a total of eight (8) subjects: Six (6) subjects randomized to the active GIC-1001 and two (2) subjects randomized to a matching placebo.
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01738425
|Algorithme Pharma Inc.|
|Montreal, Quebec, Canada, H7V 4B3|
|Principal Investigator:||Eric Sicard, MD||Algorithme Pharma Inc|