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.

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 20

Inclusion Criteria

1. Male and female subjects of 18 to 70 years old including extremes.
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).

Exclusion Criteria

1. More than 50% involvement of the most severely affected toenail.
2. An involvement of the nail matrix.
3. Lateral onychomycosis involving > 50% of the length of the most severely affected toenail.
4. Extensive hyperkeratosis (>3mm nail thickness) on the most severely affected toenail.
5. An involvement nail of the little toes only
6. Psoriasis or diabetics.
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. Clinical 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. 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, terenadine, 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.
13. Out of range laboratory values that the investigators considers as pathologic.
14. 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.
15. Breasting-feeding women and pregnant women.
16. Participation in an investigational study within 30 days prior to study entry.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Therapeutic cure i.e. mycological and clinical cure </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Scoring of individual signs and symptoms<br /><br>Measuring length of unaffected nail<br /><br>Mycological evaluation</p><br>

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