Title

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

    Phase 1
  • Study Type

    Interventional
  • Status

    Completed No Results Posted
  • Intervention/Treatment

    gic-1001 ...
  • Study Participants

    80
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.
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.
Study Started
Nov 30
2012
Primary Completion
Apr 30
2013
Study Completion
May 31
2013
Last Update
Jul 19
2013
Estimate

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 names: hydrogen sulfide releasing opioid agonist

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 names: Same tablet-based excipients, without GIC-1001 (active)

GIC-1001 oral tablets Experimental

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

GIC-1001 matching placebo Placebo Comparator

Matching placebo, single or multiple dosing

Criteria

Inclusion Criteria:

Male or female volunteer

A female volunteer must meet one of the following criteria:

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

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)
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.
Volunteer aged of at least 18 years but not older than 50 years
Volunteer with a body mass index (BMI) greater than or equal to 18.50 and below 30 kg/m2
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
Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without any clinical significance
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:

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
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
History of significant gastrointestinal, liver or kidney disease that may affect drug bioavailability
Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease
Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases
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
Known presence of rare hereditary problems of galactose and /or lactose intolerance
Use of cysteine, methionine, and other sulfur containing amino acid supplements in the previous 7 days before day 1 of this study
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)
Any clinically significant illness in the previous 28 days before day 1 of this study
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
Any history of tuberculosis and/or prophylaxis for tuberculosis
Positive urine screening of ethanol and/or drugs of abuse
Positive results to HIV, HBsAg or anti-HCV tests
Females who are pregnant according to a positive serum pregnancy test
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
No Results Posted