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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 1b Clinical Study on the Analgesic Effect of GIC-1001 and GIC-1002 on Visceral Pain Under Rectal Distension and Rectal Sensory Threshold Using the Barostat Method in Male and Female Healthy Vo

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.

Detailed Summary:

The objectives of this single center, randomized, double-blinded, placebo-controlled Phase I clinical study include the evaluation of visceral pain intensity under rectal distension following the oral administration of either of two doses of GIC-1001 or of either of two doses of GIC-1002, equimolar to the first formulation, or of placebo in 90 healthy subjects.

The barostat intra-balloon pressure required to elicit pre-defined rectal sensory symptoms (i.e. first sensation, need to defecate, urgency to defecate and pain) will also be determined. Rectal sensory symptom ratings and rectal compliance under increased rectal distension will also be evaluated.

The contribution of hydrogen sulphide (H2S) to the colonic analgesic activity of GIC-1001 by comparison to that of GIC-1002 will be evaluated following steady state pharmacokinetic analysis. To further comprehend the non-linear, U shape dose response curve observed with GIC-1001 in a previous Phase II a trial.

Finally, the safety of GIC-1002 in healthy volunteers will also be evaluated.


Sponsor: gicare Pharma Inc.

Current Primary Outcome: Mean visceral pain intensity score following dosing with GIC-1001 375 mg TID [ Time Frame: 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. ]

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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Mean visceral pain intensity score following dosing with GIC-1001 500 mg TID [ Time Frame: 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 in mm on a 100-mm VAS based on 7 measurements collected at increasing rectal distension pressures from 24 to 60 mmHg following the oral administration of the GIC-1001 500 mg TID x 3 days regimen, compared to placebo.
  • Mean visceral pain intensity score following dosing with GIC-1002 345 mg TID and GIC-1002 460 mg TID [ Time Frame: 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 in mm on a 100-mm VAS, based on 7 measurements collected at increasing rectal distension pressures from 24 to 60 mmHg following the oral administration of two doses of GIC-1002 (345 mg TID and 460 mg TID x 3 days regimen), compared to placebo.
  • Barostat pressure required to elicit pre-defined rectal sensory symptoms [ Time Frame: 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. ]
    Barostat intra-balloon pressure in mm Hg required to elicit pre-defined rectal sensory symptoms (i.e. first sensation, need to defecate, urgency to defecate and pain) following the oral administration of GIC-1001 or GIC 1002, respectively at two equimolar doses
  • Rectal sensory intensity score [ Time Frame: Stage III lasts about 15 min.Intensity score recorded every minute at te same time as VAS for rectal sensory compliance... ]
    Rectal sensory intensity score (i.e. first sensation, need to defecate, urgency to defecate and pain) in mm on a 100-mm VAS following the oral administration of GIC-1001 or GIC-1002, respectively at two equimolar doses.
  • Rectal compliance under increasing rectal distension [ Time Frame: 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. ]
    Rectal compliance in ml/mmHg under increased rectal distension following the oral administration of GIC-1001 or GIC-1002, respectively at two equimolar doses.
  • Contributing hydrogen sulfide analgesia as evaluated by comparing mean visceral pain intensity score differences [ Time Frame: Approx. 35 minutes, during total barostat testing period ]
    Contribution of H2S to GIC-1001 analgesic effects in terms of mean VAS scores differences between GIC-1001 and GIC-1002 at equimolar doses.
  • Steady state pharmacokinetic AUC (ng/ml/hour) for GIC-1001 and GIC-1002 [ Time Frame: Pre-dose, 0, 24, 36, 72, 80 hours post dose ]
    Steady State pharmacokinetics of GIC-1001 and GIC-1002 at the end of their proposed dosing regimens at pre-dosing times on Treatment Days 1, 2, 3 and on Day 4 of the barostat procedure then 8 hours post-dose .
  • Number of participants with adverse events [ Time Frame: 5 days, from Treatment Day 1 until 24 hours post-barostat distension ]
    Number of subjects reporting AEs during participation
  • Number of adverse events [ Time Frame: 5 days, from Treatment Day 1 until 24 hours post-barostat distension ]
    Number of adverse events reported overall
  • ECG measures [ Time Frame: At baseline and post-barostat Day 4 ]
    Safety evaluation: Standard ECG measures
  • Normality of physical exam [ Time Frame: At baseline and post-barostat Day 4 ]
    Safety evaluation: Complete physical examination at both entry and exit
  • Normality of Proctoscopic examination [ Time Frame: On Day 4, prior and post barostat distension ]
    Safety evaluation: Evaluation of rectum
  • Standard laboratory measures (biochemistry, hematology, urinalysis) [ Time Frame: At screening, pre-dosing (baseline) and post-barostat Day 4 ]
    Safety evaluation: comparative assessment with baseline for all components


Original Secondary Outcome: Same as current

Information By: gicare Pharma Inc.

Dates:
Date Received: October 20, 2014
Date Started: October 2014
Date Completion:
Last Updated: August 8, 2016
Last Verified: August 2016