Trial Outcomes & Findings for Resin vs. Amorolfine vs. Terbinafine Treatment in Onychomycosis (NCT NCT01851590)

Last Updated: 2015-11-30

Results Overview

To analyze the rate of complete mycological cure i.e. fungal eradication in terms of negative mycological culture AND negative potassium hydroxide (KOH) stain at 4- and 10 months time-points from the beginning of the study.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

129 participants

Primary outcome timeframe

At 4- and 10 months time-points from the beginning of the study.

Results posted on

2015-11-30

Participant Flow

In November 2013, on the basis of a newspaper advertisement, a total of 129 adult volunteers were assessed for eligibility at Vääksy Medical Center, Finland. Eligible subjects were required to provide toenail samples for screening. Inclusion criteria were a positive dermatophyte culture and a positive potassium hydroxide (KOH) stain.

Of those 129 patients screened, 48 (37%) were excluded due to negative KOH staining or cultures and 8 (6%) were excluded because onychomycosis was caused by nondermatophyte mold or yeast. At baseline, 73 (57%) patients who met the entry criteria were randomly allocated to receive 1 of 3 therapies for dermatophyte onychomycosis (3 treatment arms).

Participant milestones

Participant milestones
Measure	Resin Lacquer Arm Topical treatment: 30 % Resin Lacquer (Abicin®) Resin Lacquer was administered locally in the form of lacquer (Abicin®) onto infected nail once a day for 9 months in toenail onychomycosis.	Amorolfine Lacquer Arm Topical treatment with 5 % Amorolfine Lacquer (Loceryl®) Amorolfine: Amorolfine was administered locally in the form of lacquer (Loceryl®) onto infected nail once a week for 9 months in toenail onychomycosis.	Terbinafine Arm Oral medication with 250 mg terbinafine / day Terbinafine: Terbinafine 250 mg was administered orally once a day for 3 months in toenail onychomycosis.
Overall Study STARTED	23	25	25
Overall Study At 3 Month: End of Terbinafine Treatment	23	24	22
Overall Study At 4 Month: Follow-up Visit and Control	23	24	22
Overall Study At 9 Month: End of Topical Treatments	23	24	22
Overall Study At 10 Month: Follow-up Visit and Control	23	24	22
Overall Study COMPLETED	23	24	22
Overall Study NOT COMPLETED	0	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Amorolfine Lacquer Arm Topical treatment with 5 % Amorolfine Lacquer (Loceryl®) Amorolfine: Amorolfine was administered locally in the form of lacquer (Loceryl®) onto infected nail once a week for 9 months in toenail onychomycosis.	Terbinafine Arm Oral medication with 250 mg terbinafine / day Terbinafine: Terbinafine 250 mg was administered orally once a day for 3 months in toenail onychomycosis.
Overall Study Withdrawal by Subject	0	1
Overall Study Adverse Event	0	2
Overall Study Lack of Efficacy	1	0

Baseline Characteristics

Resin vs. Amorolfine vs. Terbinafine Treatment in Onychomycosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Resin Lacquer Arm n=23 Participants Topical treatment: 30 % Resin Lacquer (Abicin®) Resin Lacquer is administered locally in the form of lacquer (Abicin®) onto infected nail once a day for 9 months in toenail onychomycosis.	Amorolfine Lacquer Arm n=25 Participants Topical treatment with 5 % Amorolfine Lacquer (Loceryl®) Amorolfine Lacquer is administered locally in the form of lacquer (Loceryl®) onto infected nail once a week for 9 months in toenail onychomycosis.	Terbinafine Arm n=25 Participants Oral medication with 250 mg Terbinafine / day Terbinafine 250 mg is administered orally once a day for 3 months in toenail onychomycosis.	Total n=73 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	18 Participants n=5 Participants	20 Participants n=7 Participants	20 Participants n=5 Participants	58 Participants n=4 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	15 Participants n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants	15 Participants n=4 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	20 Participants n=7 Participants	17 Participants n=5 Participants	58 Participants n=4 Participants
Region of Enrollment Finland	23 participants n=5 Participants	25 participants n=7 Participants	25 participants n=5 Participants	73 participants n=4 Participants
Positive mycological culture in toenail samples	23 participants n=5 Participants	25 participants n=7 Participants	25 participants n=5 Participants	73 participants n=4 Participants
BMI	25 kg/m^2 STANDARD_DEVIATION 3 • n=5 Participants	27 kg/m^2 STANDARD_DEVIATION 4 • n=7 Participants	27 kg/m^2 STANDARD_DEVIATION 4 • n=5 Participants	26 kg/m^2 STANDARD_DEVIATION 4 • n=4 Participants
Specific dermatophyte species in mycological culture Trichophyton rubrum	20 participants n=5 Participants	24 participants n=7 Participants	21 participants n=5 Participants	65 participants n=4 Participants
Specific dermatophyte species in mycological culture Trichophyton mentagrophytes	3 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants	8 participants n=4 Participants
Plasma creatinine	76 μmol/l STANDARD_DEVIATION 15 • n=5 Participants	78 μmol/l STANDARD_DEVIATION 13 • n=7 Participants	79 μmol/l STANDARD_DEVIATION 11 • n=5 Participants	78 μmol/l STANDARD_DEVIATION 14 • n=4 Participants
Plasma γ-glutamyl transferase	29 U/I n=5 Participants	21 U/I n=7 Participants	27 U/I n=5 Participants	25 U/I n=4 Participants

PRIMARY outcome

Timeframe: At 4- and 10 months time-points from the beginning of the study.

Population: Primary and secondary outcome analyses were based on the intent-to-treat (ITT) population and missing values were imputed using the last observation carried forward (LOCF) method.

Outcome measures

Outcome measures
Measure	Resin Lacquer Arm n=23 Participants Topical treatment with 30 % Resin Lacquer (Abicin®) Resin is administered locally in the form of lacquer (Abicin®) onto infected nail once a day for 9 months in toenail onychomycosis.	Amorolfine Lacquer Arm n=25 Participants Topical treatment with 5 % Amorolfine Lacquer (Loceryl®) Amorolfine is administered locally in the form of lacquer (Loceryl®) onto infected nail once a week for 9 months in toenail onychomycosis.	Terbinafine Arm n=25 Participants Oral medication with 250 mg Terbinafine / day Terbinafine 250 mg is administered orally once a day for 3 months in toenail onychomycosis.
Mycological Cure Mycological cure at 4-month	17 Percentage of participants Interval 1.0 to 34.0	28 Percentage of participants Interval 9.0 to 47.0	16 Percentage of participants Interval 0.0 to 31.0
Mycological Cure Mycological cure at 10-month	13 Percentage of participants Interval 0.0 to 28.0	8 Percentage of participants Interval 0.0 to 19.0	56 Percentage of participants Interval 35.0 to 77.0

SECONDARY outcome

Timeframe: At 4- and 10 months time-points from the beginning of the study.

Population: Intention-to-treat population, last observation carried forward.

Clinical responses to treatment were based on the proximal linear growth of healthy nail; thus, the clinical responses were classified as partial (evident proximal linear growth of healthy nail) or complete. Partial responses were defined as significant reductions in onycholysis, subungual hyperkeratosis, and streaks. A complete response was a fully normal appearance of the toenail.

Outcome measures

Outcome measures
Measure	Resin Lacquer Arm n=23 Participants Topical treatment with 30 % Resin Lacquer (Abicin®) Resin is administered locally in the form of lacquer (Abicin®) onto infected nail once a day for 9 months in toenail onychomycosis.	Amorolfine Lacquer Arm n=25 Participants Topical treatment with 5 % Amorolfine Lacquer (Loceryl®) Amorolfine is administered locally in the form of lacquer (Loceryl®) onto infected nail once a week for 9 months in toenail onychomycosis.	Terbinafine Arm n=25 Participants Oral medication with 250 mg Terbinafine / day Terbinafine 250 mg is administered orally once a day for 3 months in toenail onychomycosis.
Clinical Responses to the Treatments Partial clinical response at 4-month	0 percentage of participants	0 percentage of participants	44 percentage of participants
Clinical Responses to the Treatments Complete clinical response at 4-month	0 percentage of participants	0 percentage of participants	0 percentage of participants
Clinical Responses to the Treatments Partial clinical response at 10-month	30 percentage of participants	28 percentage of participants	36 percentage of participants
Clinical Responses to the Treatments Complete clinical response at 10-month	0 percentage of participants	0 percentage of participants	16 percentage of participants

SECONDARY outcome

Timeframe: At 10-month time-point

Cost analysis was based on the retail price (€) and consumption of a 10 ml bottle of Abicin® 30% resin lacquer, a 5 ml bottle of Loceryl® 5% amorolfine lacquer, and 98 tablets of generic 250 mg terbinafine, sold by the University Pharmacy in Helsinki, Finland, January 2014. The cost was expressed as the average treatment cost per patient; for the total cost, this average was extrapolated to the entire study treatment arm. The results show the treatment costs (€) per day per patient in each group.

Outcome measures

Outcome measures
Measure	Resin Lacquer Arm n=23 Participants Topical treatment with 30 % Resin Lacquer (Abicin®) Resin is administered locally in the form of lacquer (Abicin®) onto infected nail once a day for 9 months in toenail onychomycosis.	Amorolfine Lacquer Arm n=25 Participants Topical treatment with 5 % Amorolfine Lacquer (Loceryl®) Amorolfine is administered locally in the form of lacquer (Loceryl®) onto infected nail once a week for 9 months in toenail onychomycosis.	Terbinafine Arm n=25 Participants Oral medication with 250 mg Terbinafine / day Terbinafine 250 mg is administered orally once a day for 3 months in toenail onychomycosis.
Cost-effectiveness 1	0.15 Euros (€) Interval 0.14 to 0.15	0.21 Euros (€) Interval 0.2 to 0.21	0.56 Euros (€) Interval 0.52 to 0.59

SECONDARY outcome

Timeframe: At 10-month time-point

Outcome measures

Outcome measures
Measure	Resin Lacquer Arm n=23 Participants Topical treatment with 30 % Resin Lacquer (Abicin®) Resin is administered locally in the form of lacquer (Abicin®) onto infected nail once a day for 9 months in toenail onychomycosis.	Amorolfine Lacquer Arm n=25 Participants Topical treatment with 5 % Amorolfine Lacquer (Loceryl®) Amorolfine is administered locally in the form of lacquer (Loceryl®) onto infected nail once a week for 9 months in toenail onychomycosis.	Terbinafine Arm n=25 Participants Oral medication with 250 mg Terbinafine / day Terbinafine 250 mg is administered orally once a day for 3 months in toenail onychomycosis.
Cost-effectiveness 2	40.7 Euros (€) Interval 38.8 to 42.6	55.2 Euros (€) Interval 52.9 to 57.5	52.1 Euros (€) Interval 46.8 to 53.0

SECONDARY outcome

Timeframe: At 4-month time-point

Population: Percentage describes the proportion of patients who declared that they have been followed the instructions completely (100%).

Evaluation of compliance was based on patient self-reports of whether the treatment protocol was followed 100% (complete), 80% (good), 60% (moderate), or 40% (poor) of the time.

Outcome measures

Outcome measures
Measure	Resin Lacquer Arm n=23 Participants Topical treatment with 30 % Resin Lacquer (Abicin®) Resin is administered locally in the form of lacquer (Abicin®) onto infected nail once a day for 9 months in toenail onychomycosis.	Amorolfine Lacquer Arm n=25 Participants Topical treatment with 5 % Amorolfine Lacquer (Loceryl®) Amorolfine is administered locally in the form of lacquer (Loceryl®) onto infected nail once a week for 9 months in toenail onychomycosis.	Terbinafine Arm n=25 Participants Oral medication with 250 mg Terbinafine / day Terbinafine 250 mg is administered orally once a day for 3 months in toenail onychomycosis.
Compliance to the Treatment	100 percentage of participants	96 percentage of participants	100 percentage of participants

Adverse Events

Resin Lacquer Arm

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Amorolfine Lacquer Arm

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Terbinafine Arm

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Resin Lacquer Arm n=23 participants at risk Topical treatment with 30 % resin lacquer (Abicin®) Resin is administered locally in the form of lacquer (Abicin®) onto infected nail once a day for 9 months in toenail onychomycosis.	Amorolfine Lacquer Arm n=25 participants at risk Topical treatment with 5 % amorolfine lacquer (Loceryl®) Amorolfine is administered locally in the form of lacquer (Loceryl®) onto infected nail once a week for 9 months in toenail onychomycosis.	Terbinafine Arm n=25 participants at risk Oral medication with 250 mg terbinafine / day Terbinafine 250 mg is administered orally once a day for 3 months in toenail onychomycosis.
Gastrointestinal disorders Diarrhoea	0.00% 0/23 • Adverse effects or side-effects during the 10-month follow-up All side-effects or adverse events were recorded systematically. Information on the side-effects were specifically asked by the research coordinator during the two follow-up visits (at 4- and 10-month) and three telephone contacts. Patients were asked to contact research coordinator if any obvious or suspected side-effect would emerge.	0.00% 0/25 • Adverse effects or side-effects during the 10-month follow-up All side-effects or adverse events were recorded systematically. Information on the side-effects were specifically asked by the research coordinator during the two follow-up visits (at 4- and 10-month) and three telephone contacts. Patients were asked to contact research coordinator if any obvious or suspected side-effect would emerge.	4.0% 1/25 • Number of events 1 • Adverse effects or side-effects during the 10-month follow-up All side-effects or adverse events were recorded systematically. Information on the side-effects were specifically asked by the research coordinator during the two follow-up visits (at 4- and 10-month) and three telephone contacts. Patients were asked to contact research coordinator if any obvious or suspected side-effect would emerge.
Skin and subcutaneous tissue disorders Rash	0.00% 0/23 • Adverse effects or side-effects during the 10-month follow-up All side-effects or adverse events were recorded systematically. Information on the side-effects were specifically asked by the research coordinator during the two follow-up visits (at 4- and 10-month) and three telephone contacts. Patients were asked to contact research coordinator if any obvious or suspected side-effect would emerge.	0.00% 0/25 • Adverse effects or side-effects during the 10-month follow-up All side-effects or adverse events were recorded systematically. Information on the side-effects were specifically asked by the research coordinator during the two follow-up visits (at 4- and 10-month) and three telephone contacts. Patients were asked to contact research coordinator if any obvious or suspected side-effect would emerge.	4.0% 1/25 • Number of events 1 • Adverse effects or side-effects during the 10-month follow-up All side-effects or adverse events were recorded systematically. Information on the side-effects were specifically asked by the research coordinator during the two follow-up visits (at 4- and 10-month) and three telephone contacts. Patients were asked to contact research coordinator if any obvious or suspected side-effect would emerge.

Additional Information

Janne Jokinen, MD, PhD, Consultant Cardiothoracic Surgeon

Department of Cardiac Surgery, Heart and Lung Centre, Helsinki University Hospital, Finland

Phone: 50 554 8103

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place