An open label phase IIa trial to assess efficacy and tolerability of a once a week oral dose of 200 mg R126638 in disto-lateral toenail onychomycosis. - R126638 in toenail onychomycosis

• Conditions: Onychomycosis; MedDRA version: 8.1Level: LLTClassification code 10030338Term: Onychomycosis

• Registration Number: EUCTR2005-004611-30-NL
• Lead Sponsor: Barrier Therapeutics nv

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-07-05
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1.Male and female subjects 18 to 70 years old, inclusive.
2.Clinical diagnosis of disto-lateral onychomycosis of the toenails.
3.Diagnosis confirmed by microscopic examination and culture.
4.If the subject is of childbearing potential, she must have a negative urine pregnancy test at inclusion and agree to use effective forms of birth control (double barrier method) during the duration of the clinical trial or until the first menses after 60 days following the last dose of study medication, whichever is longer. She must be on a stable regimen, for at least one month, of oral contraceptives, contraceptive implant or depot injection, contraceptive patch, IUD, condom and spermicidal agent or diaphragm and spermicidal agent.
5.Availability of a signed informed consent prior to beginning protocol-specific procedures, indicating an understanding of the purpose of this trial and a willingness to adhere to the treatment regimen and trial procedures described in this protocol.
6.The subject is in good health and free of any disease or physical condition which, in the investigator’s opinion, might impair evaluation of onychomycosis of the toenail(s).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Distolateral-toenail onychomycosis with involvement of the lanula.
2.An involvement of the nail matrix.
3.Longitudinal yellow streaks on the affected toenail
4.Extensive hyperkeratosis (>3mm nail thickness) on the most severely affected toenail.
5.Toe nail onychomycosis limited to little toe nails only.
6.Psoriasis or diabetes.
7.History of significant sensitivity, or significant allergy to azoles or related drugs or any ingredient in the study medication.
8.Severe coexisting hepatic, renal, or bone marrow disease, hyperlipidemia, chronic pancreatitis, or a history indicating adrenal cortex dysfunction or any other serious disease (including cancer and subjects known to be HIV positive).
9.History of heart-failure, myocardial infarction within the past six months, cardiac arrhythmia, or under treatment for heart disorders.
10.Clinically significant abnormal ECG-intervals or morphology of the ECG, QT or QTc>450 ms.
11.Use of any local or systemic anti-mycotic therapy two weeks (local) or three months (systemic) before treatment.
12.Any use of nail polish or acrylic nails is prohibited on the toenails.
13.Medications that reduce gastric acidity may potentially interfere with azole absorption. Use of H2-receptor blockers and proton-pump inhibitors within the 7 days period prior to dosing or within 4 hours after dosing of study medication. Antacids may not be taken within 4 hours after dosing.
14.Current use of prohibited medication. CYP3A4 metabolized substrates such as triazolam, oral midazolam, alprazolam, buspirone, Ca-channel blockers such as dihydropyridines and verapamil, tiralazad, fentanyl, alfentanyl, coumarins; CYP3A4 metabolized HMG-CoA reductase inhibitors such as lovastatin, simvastatin, atorvastatin, pravastatin; potent enzyme inducers of CYP3A4, e.g. phenytoin phenobarbital, carbamazepine, isoniazid, rifampin, rifabutin; potent inhibitors of CYP3A4, e.g. ritonavir, indinavir and saquinavir; drugs known to prolong QT-interval such as class Ia and III antiarrythmics, sotalol, terfenadine, astemizole, cisapride, levacetylmethadol (levomethadyl), misolastine, azolastine, antimalarials such as chloroquine, quinidine and halofantrine, macrolides, quinolones, antipsychotics; systemic immunosuppressants e.g. cyclosporine and tacrolimus, rapamycin (sirolimus), methotrexate, 6-mercaptopurine; systemic corticosteroids.
15.Out of range laboratory values that the investigators consider as pathologic.
16.History or suspicion of alcohol abuse or drug abuse, or psychological or other emotional problems which, in the investigator’s opinion, are likely to invalidate informed consent, or limit the ability of the subject to comply with the protocol requirements.
17.Females who are nursing or are pregnant.
18.Participation in an investigational study within 30 days prior to study entry.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objective of this open label phase IIa exploratory trial is to evaluate the efficacy and tolerability of a once a week oral dose of 200 mg R126638, for 12 weeks, for the treatment of toenail onychomycosis. <br>Efficacy is assessed by therapeutic cure (mycological and clinical cure) (primary endpoint);Secondary Objective: Secondary endpoints are scoring of individual signs and symptoms, measuring length of unaffected nail and mycological evaluation;Primary end point(s): The primary efficacy variable will be defined as therapeutic cure of the target toenail, i.e. both mycological eradication and clinical cure (clearance of all signs and symptoms) at 12 weeks after start of treatment.