Evaluation of the Response of Itraconazole and Terbinafine Therapy in Subjects With Crohn's Disease

Evaluation of the Response of Itraconazole and Terbinafine Therapy in Subjects With Crohn's Disease Not Responding Adequately to Current Therapy

This study will evaluate the response of itraconazole and terbinafine therapy compared to placebo in patients with mild to moderate Crohn's disease (CD).

This multicenter, randomized, double-blind, placebocontrolled, phase II, proof of concept study will randomize 68 subjects at 2 to 5 clinical sites in Canada. Following signature of informed consent, subjects who meet entry criteria will be randomized in a 1:1 ratio to receive either itraconazole and terbinafine, or matching placebos. During the first 4 weeks subjects will receive itraconazole 200 mg twice daily or matching placebo, followed by itraconazole 200 mg twice daily and terbinafine 250 mg twice daily or matching placebos for the remaining 16 weeks. The 2 drugs will be administered orally.

Inclusion Criteria:

• Subjects with endoscopy/radiology confirmation of active disease within 6 months prior to enrolment;
• Mild to moderate active CD defined by the HBI score of ≥ 5 to ≤ 16 at baseline;
• Female of childbearing potential must have a negative urine pregnancy test at screening and at randomization baseline Visit 2. Women are considered not of childbearing potential if they either:
• Have had a hysterectomy or tubal ligation prior to baseline visit or;
• Are postmenopausal defined as no menses for 12 months or a FSH level (if available) in the menopausal range.
• Women of childbearing potential must agree to use an effective double method of birth control throughout the study: barrier method (e.g. male or female condoms, spermicides, sponges, foams, jellies, and diaphragm) in combination with other methods of contraception including implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, intrauterine devices, abstinence, or a sterile sexual partner.
• Subjects with the capacity to provide informed consent.

Exclusion Criteria:

• Subject with a current diagnosis of ulcerative colitis (UC);

• Contraindication to the use of itraconazole including congestive heart failure, ventricular dysfunction, ventricular arrhythmia, or negative inotropic state;

• Subjects with elevated or abnormal liver enzymes (ALT/AST>3 ULN) or patients with pre-existing chronic or active liver disease at screening;

• Female subject who is pregnant, planning to become pregnant during the study, or breastfeeding;

• Subject with renal impairment (creatinine clearance ≤ 50 mL/min using Cockcroft-Gault equation);

• Subject with a known hypersensitivity to itraconazole, terbinafine, or any of their excipients;

• Subjects on medications which interact with itraconazole: methadone, pimozide, quinidine or other CYP3A4 inhibitors;

• Positive C. difficile toxin test at screening;

• Use of steroid greater than 20 mg/day;

• Change of steroid dosage in the 2 weeks prior to enrolment;

• Change in CD therapy:

  • The Anti-TNFs, anti-integrins, anti-IL12/23 in the 4 months prior to enrolment;
  • Thiopurines or methotrexate (MTX), in the 2 months prior to enrolment;

• Participation in other clinical trial within 30 days of signing the Information and Consent Form (ICF).