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

NCT01738425 | Completed Phase 1 DMC

• 1 other identifier: GIC P2-458
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colonic Diseases

Keywords

GIC-1001; opioid agonist; sulfide; colonoscopy; gicare; Phase I; safety; tolerability; pharmacokinetics; healthy subjects; single ascending dose; multiple ascending dose; SAD; MAD; food effect

Outcome Measures

Primary Outcomes (1)

• Change in physical status

  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.

  8 hours post- drug administration

Secondary Outcomes (3)

• Pharmacokinetics

  Up to 36 hours for single ascending doses; every day and up to 8 hour post last dose for multiple ascending doses

• Change in ECG recording

  3 hours post drug administration

• Cardiac monitoring

  23 hours post drug administration

Study Arms (2)

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

Drug: GIC-1001; 125 mg oral tablets

GIC-1001 matching placebo

PLACEBO COMPARATOR

Matching placebo, single or multiple dosing

Drug: GIC-1001 matching placebo

Interventions

GIC-1001; 125 mg oral tablets DRUG

Single ascending doses (SAD) from 125 mg to 1000 mg; Multiple ascending doses from 125 mg to 500 mg, TID over 7 successive days

Also known as: hydrogen sulfide releasing opioid agonist

GIC-1001 oral tablets

GIC-1001 matching placebo DRUG

Single ascending doses (SAD) \[equivalent to active arm, 125 mg to 1000 mg\] Multiple ascending doses, TID over 7 successive days \[equivalent to the active arm, 125 mg to 500 mg\]

Also known as: Same tablet-based excipients, without GIC-1001 (active)

GIC-1001 matching placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• gicare Pharma Inc.: lead

Study Sites (1)

Algorithme Pharma Inc.

Montreal, Quebec, H7V 4B3, Canada

Location

Related Publications (1)

• Paquette JM, Rufiange M, Iovu Niculita M, Massicotte J, Lefebvre M, Colin P, Telmat A, Ranger M. Safety, tolerability and pharmacokinetics of trimebutine 3-thiocarbamoylbenzenesulfonate (GIC-1001) in a randomized phase I integrated design study: single and multiple ascending doses and effect of food in healthy volunteers. Clin Ther. 2014 Nov 1;36(11):1650-64. doi: 10.1016/j.clinthera.2014.08.005. Epub 2014 Sep 15.

  PMID: 25224876 DERIVED

MeSH Terms

Conditions

Colonic Diseases

Interventions

trimebutine 3-thiocarbamoylbenzenesulfonate; Exercise

Condition Hierarchy (Ancestors)

Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Eric Sicard, MD

  Algorithme Pharma Inc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2012
• First Posted: November 30, 2012
• Study Start: November 1, 2012
• Primary Completion: April 1, 2013
• Study Completion: May 1, 2013
• Last Updated: July 19, 2013

Record last verified: 2013-07

Locations

CA (1)