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Early and visible improvements after application of k101 in the appearance of nails discoloured and deformed by onychomycosis

Journal of Cosmetics, Dermatological Sciences and Applications, 2011, 1, 59-63
doi:10.4236/jcdsa.2011.13010 Published Online August 2011 (http://www.SciRP.org/journal/jcdsa)
Early and Visible Improvements after Application
of K101 in the Appearance of Nails Discoloured
and Deformed by Onychomycosis
Jan Faergemann1, Sören Gullstrand2, Kjell Rensfeldt3
1Department of Dermatology, Sahlgrenska University Hospital, Gothenburg, Sweden; 2Möllevångens Husläkargrupp, Malmö, Swe-
den; 3Moberg Derma AB, Bromma, Sweden.
Email: [email protected]
Received June 9th, 2011; revised July 14th, 2011; accepted July 19th, 2011.

ABSTRACT
Onychomycosis is a fungal infection of the nails of the fingers and toes and is difficult to cure. A previous 24-week,
placebo-controlled study demonstrated that a solution containing propylene glycol, urea and lactic acid (K101) was
well-tolerated and effective in the treatment of onychomycosis. Patients who received K101 judged that their condition
had improved from Week 2 of treatment onwards. The aim of the current study was to further evaluate and document
early visible effects on nail appearance after application of topical K101 in an 8-week baseline-controlled study in 75
patients. Patients graded the appearance of their nail compared with baseline using a four-point scale. Compared with
baseline, 91.8% (67/73; 95% confidence interval (CI): 83.0%, 96.9%) of the patients experienced at least some im-
provement in their target nail after 8 weeks of treatment. At Week 2, the proportion showing some improvement was
76.7% (56/73; 95% CI: 65.4%, 85.8%) with this number increasing to 87.7% (64/73; 95% CI: 77.9%, 94.2%) at Week 4.
Proportions of patients reporting less thickened, less discoloured, less brittle and softer nails increased over the course
of the study. No safety issues were identified. In conclusion, K101 provided early visible improvements in nails affected
by onychomycosis.

Keywords: K101, Onychomycosis, Early Effects, Topical
1. Introduction
can include fatal liver toxicity [8]. Topical agents are usually formulated as lacquers that adhere to the nail Onychomycosis is a fungal infection that affects the nails plate and include antifungal drugs such as amorolfine, of the hand and foot. Infection rates in Western adult tioconazole and ciclopirox 8% [5,7]. Topical application populations range from 2% to 14%, although onycho- allows targeted delivery to infected areas, minimising the mycosis may affect up to 50% of people over 70 years of risk of secondary effects related to systemic exposure. age [1]. Prevalence of onychomycosis is also higher in the immuno-compromised, children with Down's syn- K101, a topical treatment for onychomycosis, is a drome and patients with diseases that affect the periph- combination of propylene glycol, urea and lactic acid. eral circulation, such as diabetes mellitus [2,3]. Ony- The concept of using propylene glycol solutions of urea chomycosis is often associated with pain and discomfort and lactic acid to treat onychomycosis was investigated coupled with a significant negative impact on emotional in a study of 23 patients who applied a test solution twice health and social image [4,5]. daily for 2 - 6 months. The solution was effective in 21 Onychomycosis can be treated pharmacologically with of the 23 patients treated [9]. The efficacy of K101 was both systemic and topical agents [6]. Systemic antifungal confirmed in a placebo-controlled study that documented drugs such as terbinafine and itraconazole are effective the efficacy and tolerability of K101 versus placebo in treatments; although their use must be balanced against 493 patients with onychomycosis. A greater number of the risk of unpleasant side-effects that include gastroin- patients who received K101 experienced mycological testinal disorders, skin rashes and headache [5,7]. Serious cure after 26 weeks of treatment (27% versus 10%) [10]. side-effects occur in less than 1% of patients, but these Also, almost half the patients who received K101 con- Copyright 2011 SciRes. JCDSA
Early and Visible Improvements after Application of K101 in the Appearance of Nails Discoloured and
Deformed by Onychomycosis
sidered that their condition had shown at least some im- tients. Photographs were taken at baseline and after 2, 4 provement from Week 2, and approximately 75% from and 8 weeks of treatment. Patients were asked the fol- Week 8 of treatment onwards. In the light of these find- lowing question: "How do you perceive your target nail ings, and to investigate in more detail the early clinical appearance compared to baseline?", and then evaluated effects of K101, we conducted an 8-week study in pa- the efficacy of their treatment using a four-point Global tients with nails affected by onychomycosis. Assessment Scale. The scores used were: 1) no im- provement; 2) some improvement; 3) clear improvement; 2. Methods
and 4) very good improvement. Patients were also asked 2.1. Study Population
whether the target nail had become less thickened, dis- coloured or brittle and whether it had softened. The study population comprised men and women aged at least 18 years with clinically diagnosed onychomycosis 2.4. Safety Assessments
affecting between 25% and 75% of at least one big toe- Adverse events were recorded from the start of the first nail or thumbnail. Patients were excluded if they had treatment period to the end of the study. At each study proximal subungual onychomycosis or other conditions visit, investigators asked patients the following question: known to cause abnormal nail appearance. Patients who "Have you had any health problems since your last had participated in another study with K101 or in any visit?". The Investigator rated any reported events for study with an investigational drug or device within 4 intensity and relationship to study treatment. weeks of screening were ineligible, as were patients who had used topical antifungal nail treatment within 1 month 2.5. Statistical Analysis
or systemic antifungal treatment within 3 months of Seventy patients were to be enrolled to provide 65 screening. Patients with a known allergy to any of the evaluable patients. With a sample size of 65, a two-sided study treatment components were excluded from the 95% confidence interval (CI) for the proportion of study. The study was conducted at Sahlgrenska Univer- patients who experienced at least some improvement in sity Hospital (Gothenburg, Sweden) and Möllevångens target nail appearance (who scored 2 or more according Husläkar-grupp (Malmö, Sweden) after approval by the to the Global Assessment Scale) after 8 weeks' treatment, Regional Ethics Committee (Gothenburg, Sweden). All was to extend 0.12 from the observed proportion for an patients provided signed and dated informed consent expected proportion of 0.50. prior to screening. The primary efficacy endpoint was an improvement in 2.2. Study Design
target nail appearance at 8 weeks compared with baseline, which was defined as the proportion of patients scoring This was an 8-week baseline-controlled study to assess at least 2 on the Global Assessment Scale. Other end- the efficacy of K101 in improving nail appearance. At points included the proportion of patients scoring at least the baseline visit at the study site, patients were taught 2 on the Global Assessment Scale at Week 2 and Week 4 how to apply K101 by study staff. K101 is a clear, col- and individual nail attributes at Week 2, Week 4 and ourless liquid supplied in a 10 mL plastic tube with a Week 8. All efficacy endpoints were presented as point silicon drop tip to ensure accurate application to the af- estimates with two-sided 95% CIs computed using the fected nail. A thin layer of the K101 solution was applied Clopper-Pearson (exact) method. Adherence was calcu- to all affected fingers and/or toenails at bedtime every day. An affected big toenail or thumbnail was selected as lated as the percentage of maximum use of K101. The safety analysis set comprised all randomised pa- the target nail for all subsequent assessments. After their tients who applied study medication at least once. The visit at baseline, patients returned 2, 4 and 8 weeks after per protocol set was a subset of the full analysis set and starting treatment to undergo efficacy and safety evalua- consisted of patients with 80% adherence who had not tions. At each study visit after starting treatment, patients experienced major protocol violations and who had a were asked "On average, how many days per week have measure of the primary endpoint. SAS® software (ver- you applied the test product since last visit?". sion 9.2, SAS Institute Inc., Cary, NC, USA) was used 2.3. Efficacy Assessments
for the statistical analysis. The target nail was photographed in a standardised way 3. Results
using a digital camera and camera stand; the stand was 3.1. Patient Disposition
equipped with lighting to create consistent light condi- tions. Care was taken to ensure that the distance between Seventy-five patients were enrolled and 72 completed the the camera and the nail was exactly the same for all pa- study. The mean age of the patients was 60 years. Most Copyright 2011 SciRes. JCDSA

Early and Visible Improvements after Application of K101 in the Appearance of Nails Discoloured and
Deformed by Onychomycosis
patients were male (63.5%) and Caucasian (97.3%). Table 3. Patient assessment of individual nail attributes (full
Three patients were discontinued from the study: one due analysis set; N = 73).
to protocol non-compliance and two due to non-atten- dance at follow-up visits. All patients had abnormal fin- ger and/or toenails and 22 (29.7%) had abnormal skin on hands and feet as a result of fungal infection. Overall, mean (standard deviation) adherence was 99.45 (2.3) % (full analysis set). 3.2. Efficacy Results
The proportion of patients experiencing at least some improvement of the target nail at 8 weeks, compared with baseline, was 91.8% (67/73 patients; 95% CI; 83.0, 96.9) (Table 1. full analysis set). After 2 weeks of treat-
ment, 76.7% (56/73) of patients experienced at least some improvement of the target nail; this proportion in- CI: confidence interval. creased to 87.7% (64/73) after 4 weeks. Similar results
were obtained for the per protocol data set. During the
treatment period, the number (%) of patients reporting
clear/very good improvement of the target nail increased
from nine (12.4%) at Week 2 to 38 (52.0%) at Week 8
(Table 2).
Over the 8 weeks of the study, increasing proportions of patients reported that, compared with baseline, their
target nails were less thickened (from 32.9% at Week 2
to 75.3% at Week 8), less discoloured (from 60.3% to
67.1%), less brittle (from 15.1% to 45.2%) and softened
(from 35.6% to 71.2%) (Table 3). Visible improvements
in the condition of the target nails from baseline to Week
8 are presented in Figure 1 for a patient with infection of
moderate baseline intensity and in Figure 2 for a patient
Figure 1. Photographic sequence showing target nail ap-
with infection of severe baseline intensity. In the course pearance at baseline (Panel A), at Week 2 (Panel B), Week 4
(Panel C) and Week 8 (Panel D) for a patient with onycho-
of treatment, visible signs of fungal infection regressed mycosis of moderate intensity at baseline.
Table 1. Improvement in target nail (defined as a score ≥ 2
on the Global Assessment Scale).
Full analysis set (N = 73) Per protocol set (N = 71) CI: confidence interval
Table 2. Patient experience of target nail appearance com-
pared with baseline (full analysis set; N = 73)
Figure 2. Photographic sequence showing target nail ap-
Some improvement pearance at baseline (Panel A), at Week 2 (Panel B), Week 4
Clear improvement (Panel C) and Week 8 (Panel D) for a patient with onycho-
Very good improvement mycosis of severe intensity at baseline.
Copyright 2011 SciRes. JCDSA
Early and Visible Improvements after Application of K101 in the Appearance of Nails Discoloured and
Deformed by Onychomycosis
and in general, a more uniform and smooth appearance study; no adverse events were judged to be treat- was observed throughout the nail. ment-related by the Investigator. In a 24-week long, dou- 3.3. Safety and Tolerability
ble-blind, placebo-controlled study with K101, irrita- tion/pain was observed in the periungual skin in 22 Eight patients (10.8%) experienced nine adverse event (6.4%) patients who received K101. In that study, K101 episodes; none of these was judged to be related to K101 was applied to the nail drop-wise, which presumably by the Investigator. Seven of the events were considered increased the likelihood that the solution would contact to be mild and two were moderate in intensity. The most and leach into the skin surrounding the infected nail. frequently reported adverse event was rhinorrhoea (n = Also, the target nail was occluded with surgical tape for the first 4 weeks of treatment, which may have amplified 4. Discussion
skin irritation. In the current study, the applicator con- sisted of a tube with a silicon tip so that the K101 solu- This 8-week, open-label study was designed to evaluate tion could be spread more precisely over the nail surface, the early clinical effects of treatment with K101 in pa- thus minimising the risk for irritation or pain in the peri- tients with onychomycosis. Efficacy was assessed in ungual skin. Photographs from the current study showed terms of improvement from baseline in nail appearance. that, in some cases, the treated nails became more opaque. Standardised photographic techniques were used to However, this was not reflected in the adverse event re- document at regular intervals any changes in appearance porting indicating that patients did not consider this to be from baseline. With just 2 weeks of treatment the propor- tion of patients with visible improvements in the target In conclusion, data from the current study support ear- nail was of 76.7% and this number increased to 91.8% by lier findings that clearly demonstrate rapid improvements Week 8 (primary endpoint). As the study progressed, in nail condition after application of K101; early, visible, treatment was associated with the retreat of typical signs positive effects compared with baseline were observed of fungal nail infection such as the development of a less from 2 weeks onwards. This topically applied solution discoloured and smoother nail surface. also appears to demonstrate characteristics conducive to When rating the condition of their nails for thickness, good adherence such as an excellent tolerability profile discolouration, brittleness and softness, patients generally and once daily application. reported improvements from baseline at Week 2, Week 4 5. Acknowledgements
and Week 8. These data support the findings of a previ-ous study in which half the patients enrolled (152/304 The authors would like to thank the patients and staff who participated patients) perceived at least some improvement in their in the study. This study was funded by Moberg Derma AB. condition after only 2 weeks of treatment [10]. There are limited data within the scientific literature REFERENCES
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