A Clinical Phase I Study on GIC-1001 in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
gicare Pharma Inc.
ClinicalTrials.gov Identifier:
NCT01738425
First received: November 23, 2012
Last updated: July 17, 2013
Last verified: July 2013
  Purpose

The objectives of this single center, randomized, double-blinded, placebo-controlled Phase I clinical study are to evaluate the safety and tolerability of five (5) single and four (4) multiple increasing oral doses of GIC-1001 compared to placebo, and to evaluate the pharmacokinetics of GIC-1001 following single and multiple-dose administration in 80 healthy, 18-50 years old male and female subjects. Moreover, the effect of food on the pharmacokinetics of GIC-1001 in healthy subjects will be assessed. This study is designed with an integrated, adaptive approach which allows the evaluation of single and multiples doses of GIC-1001 in a progressive, overlapped fashion.


Condition Intervention Phase
Colonic Diseases
Drug: GIC-1001; 125 mg oral tablets
Drug: GIC-1001 matching placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by gicare Pharma Inc.:

Primary Outcome Measures:
  • Change in physical status [ Time Frame: 8 hours post- drug administration ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]

    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.



Enrollment: 80
Study Start Date: November 2012
Study Completion Date: May 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Male or female volunteer
  2. A female volunteer must meet one of the following criteria:

    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.

      or

    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.
  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)

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01738425

Locations
Canada, Quebec
Algorithme Pharma Inc.
Montreal, Quebec, Canada, H7V 4B3
Sponsors and Collaborators
gicare Pharma Inc.
Investigators
Principal Investigator: Eric Sicard, MD Algorithme Pharma Inc
  More Information

No publications provided

Responsible Party: gicare Pharma Inc.
ClinicalTrials.gov Identifier: NCT01738425     History of Changes
Other Study ID Numbers: GIC P2-458
Study First Received: November 23, 2012
Last Updated: July 17, 2013
Health Authority: Canada: Health Canada

Keywords provided by gicare Pharma Inc.:
GIC-1001
opioid agonist
sulfide
colonoscopy
gicare
Phase I
safety
tolerability
pharmacokinetics
healthy subjects
single ascending dose
multiple ascending dose
SAD
MAD
food effect

Additional relevant MeSH terms:
Colonic Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Analgesics, Opioid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants

ClinicalTrials.gov processed this record on April 15, 2014