Skin reactions in a phase 3 study of a testosterone topical solution applied to the axilla in hypogonadal men

Abstract

Objective:

Axiron (testosterone topical solution 2%) is an approved topical testosterone replacement therapy applied to the axilla. The axilla is a novel application site for testosterone replacement therapy, with differences in skin structure and exposure that could impact the type and/or severity of skin reactions observed with testosterone topical solution 2%. We therefore present a detailed description of data from a pivotal clinical trial regarding the incidence, time of onset, duration, and severity of patient-reported skin reactions as well as visual assessments made by investigators and rated using Draize scoring.

*Axiron is a trademark of Eli Lilly and Company, Indianapolis, IN, USA.

Methods:

Data were analyzed from a multinational, open-label, clinical study in which a 2% testosterone topical solution was applied to the axilla in hypogonadal men. The primary study was for 120 days (N = 155) with a 60-day extension that evaluated skin safety (N = 71). At each visit investigators asked patients about adverse skin reactions (including those occurring between study visits); visually assessed the application site; and graded observed instances of erythema or edema using Draize scoring (rated from 0 to 4).

Results:

Application-site irritation following study drug application was the most commonly reported event (n = 12 patients) and was generally mild (n = 11; moderate, n = 1) in severity. Application-site irritation did not increase in severity over time and led to only one discontinuation. Erythema was the second most common patient-reported skin reaction (n = 10 patients) and was also generally mild (n = 9; moderate, n = 1). Draize scoring rated all directly observed cases of erythema as grade 1 (very slight, 6 patients) or grade 2 (well-defined, two patients), and identified two instances of erythema not reported by patients. Erythema was typically transient, and in most cases resolved without interruption of therapy. Three cases of edema were reported by patients, and two of these were also identified by visual inspection; all cases of edema occurred in conjunction with erythema. Two cases of acne (facial, shoulders) and one of folliculitis (scalp) were also reported.

Conclusions:

Skin reactions were observed in a minority of patients, were mild or at most moderate in severity, and seldom led to discontinuation.

Keywords::

• Adverse event
• Androgen
• Application site reaction
• Axilla
• Draize method
• Men
• Testosterone
• Topical

Transparency

Declaration of funding

This research project was funded by Eli Lilly and Company, and describes data obtained from a study originally funded by Acrux Pty. Ltd.

Declaration of financial/other relationships

E.A.K. and D.M. were employees and stockholders of Eli Lilly and Company. T.M. is an employee of PharmaNet/i3, and provided medical writing services for the manuscript, working under contract with Eli Lilly and Company.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors would like to acknowledge Gordon Berry of Eli Lilly and Company for editorial assistance, Jennifer Jarvis of Eli Lilly and Company for assistance with data collection, and Bobbi McLean of PharmaNet/i3 for technical assistance in the preparation of this manuscript.

Notes

*Axiron is a trademark of Eli Lilly and Company, Indianapolis, IN, USA.