A Randomized, Double-blind, Placebo-Controlled Proof of Concept Trial of Topical Cidofovir, 1% and 3%, for the Prevention of Beard Hair Growth in Men FREE

Unwanted facial hair, hirsutism, and pseudofolliculitis barbae occur commonly, and billions of dollars are spent annually on hair removal products.^1- 2 Eflornithine, the only prescription topical agent approved in the United States for female facial hirsutism, has only a 32% success rate and has not been evaluated in men.¹ Therefore, additional topical treatments effective in preventing hair growth are needed. The antiviral agent cidofovir has been reported to induce local alopecia when applied topically.³ In this study, we evaluate the efficacy and safety of topical cidofovir in preventing beard hair growth in healthy men.

Eligible participants were men who shaved daily and had beards scoring 4 (dense) or 5 (very dense) on the physician global assessment (PGA) of hair density.⁴ Subjects were excluded if they used any medication affecting hair growth or had a history of alopecia areata. The study was approved by the institutional review board and registered at ClinicalTrials.gov (NCT00948506).

Subjects were randomized as to which side of the face received cidofovir or placebo and to either the 1% or 3% concentration. Cidofovir and placebo were applied once daily after shaving to a circular area (2.5-cm diameter) within the beard in a split-face design. Templates delineating the treatment area were used in drug application and evaluation.⁴ Treatment duration was increased from 6 to 8 weeks following an interim analysis of the first 5 subjects. Subjects were evaluated every 2 weeks during treatment; those receiving 6-week treatment were evaluated post treatment at weeks 8 and 10, while those receiving 8-week treatment were seen at weeks 10 and 12 only if they had a PGA change or unresolved adverse event at week 8. Subjects did not shave for 48 hours before visits to grow visible hair for assessment.

At each visit, the investigator performed a PGA and photographed the treatment areas. The number of hairs within the treatment area in each photograph were counted as previously described.⁴ Laboratory test results, including for renal and liver function, were assessed at baseline and every 2 to 4 weeks.

The primary outcome was response to treatment, which was defined as a PGA score of 2 (sparse) or lower at the end of treatment. We compared response rates and hair count changes between cidofovir and placebo sites in both intention-to-treat and as-treated populations. Data were analyzed using Stata IC, version 10 (StataCorp LP).

Of 39 subjects screened, 20 were enrolled. Seventy percent of subjects were white (n  =  14), 15% black (n  =  3), and 15% Asian (n  =  3). The median age of subjects was 32 years (interquartile range, 26-42 years). Four subjects withdrew during treatment owing to scheduling conflicts and health problems unrelated to the study. Sixteen subjects (8 each in the 1% and 3% groups) completed treatment, and 11 subjects followed up post treatment. Baseline PGA scores and hair counts did not differ significantly between the active and placebo groups or between the 1% and 3% groups (Table). All subjects had normal baseline blood urea nitrogen and creatinine levels.

We observed a 5% (95% confidence interval 0.1%-24.9%) response rate in the cidofovir and placebo groups (Table). Hair count changes did not differ significantly between the cidofovir and placebo sites. However, we observed a negative trend in hair counts within the 3% group compared with placebo (median difference in hair count changes [ Δ Δ] −73) (P  =  .08).

Twelve subjects experienced 24 adverse events, the most common being upper respiratory infection (20%; [n  =  4]), headache (15%; [n  =  3]), and erythema and/or hyperpigmentation (15%; [n  =  3]), or pruritus of the treatment area (10%; [n  =  2]). However, all local skin reactions were mild and dose independent, did not require stopping application of the drug, and resolved with little or no intervention by 8 weeks after treatment cessation. No significant changes in laboratory values were observed.

The negative trend in hair count with use of cidofovir, 3%, suggests a dose-response relationship and that the 3% concentration may be promising for preventing hair growth. We did not observe induction of total alopecia as was previously reported when topical cidofovir was applied to virally infected skin of immunocompromised patients.³ Treatment dose and duration may have been insufficient to trigger cidofovir's effect in normal skin. Nevertheless, topical cidofovir was well tolerated and showed an incidence of local skin reactions similar to that of eflornithine.¹

Limitations of this trial include the low statistical power of a small study. The use of templates to localize the treatment area may have introduced variability in drug application or evaluation. Finally, preventing facial hair growth in men may be a high-efficacy bar relative to preventing facial hair growth in women; cidofovir likely needs to reach the rapidly proliferating bulb matrix cells in the deepest portion of the follicle, which reside deeper in male beard follicles than female facial follicles.⁵

In conclusion, topical cidofovir was safe and well tolerated, and the 3% concentration may be promising for further studies of hair growth prevention. Future trials evaluating higher concentrations, longer treatment durations, and use in women are warranted.