Single ascending dose safety, tolerability, and pharmacokinetic study of econazole in healthy volunteers

ABSTRACT

Introduction

Econazole has been found efficacious as antitubercular in in vitro and in vivo animal studies. However, limited information is available for its safety and pharmacokinetics in humans. In our present study we have conducted single ascending dose, safety, and pharmacokinetic evaluation in healthy human volunteers with the purpose of enabling translation for tuberculosis.

Methods

This study was conducted as a single-center, ascending-dose, placebo-controlled, double blind design. Three ascending dose were chosen (250 , 500 , and 1000 mg) to be administered as a single oral dose. The volunteers were screened for potential eligibility. Participants were randomized to receive either Econazole or Placebo in a 6:2 design. Safety assessments and pharmacokinetic evaluations were carried out for each cohort.

Results

Econazole was found to be safe at all dose levels. No serious or severe adverse events occurred during the study. The AUC (0–∞) showed a response relationship with a value of 49 ± 3.47 h* µg/ml, 17. 86 ± 8.40 hr* µg/ml, 35.54 ± 13.94 hr* µg/ml for 250 mg, 500 mg, and 1000 mg, respectively.

Conclusion

Based on the findings of our study, a dose of 500 mg Econazole, once a day orally was considered as appropriate for further evaluation.

KEYWORDS:

• Econazole
• Phase 1 study
• pharmacokinetic evaluation
• multi drug resistant tuberculosis
• healthy volunteers

Acknowledgments

We would like to acknowledge ICMR for providing with funding support and providing guidance during the study conduct through the subject expert committee.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Ethical approval

The study had been approved by Institute Ethics Committee.

Additional information

Funding

ICMR had provided funding support through the grant No: 5/8/5/12/ITRC-Therapeutics/2019/ECD.