Safety and Efficacy Study of Subjects With Onychomycosis of the Great Toenail

An Open-Label, Rising Multiple-Dose, Multi-Center Study to Evaluate the Safety and Efficacy of Topically Applied AN2690 5.0% and 7.5% Solution for the Treatment of Adult Subjects With Onychomycosis of the Great Toenail

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01278394

Enrollment

Registered

2011-01-17

Start date

2007-03-31

Completion date

2008-07-31

Last updated

2018-12-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Onychomycosis

Keywords

Onychomycosis, Fungal Nail

Brief summary

The purpose of the study is to determine the safety and efficacy of 5.0% AN2690 Solution in the treatment of distal, subungual onychomycosis of the great target toenail.

Detailed description

In this cohort, only the targeted great toenail identified at Baseline prior to the commencement of treatment from culture results collected at the Screening visit were evaluated for primary efficacy whereas all treated toenails were evaluated for safety. At each visit, the investigator was asked to make a clinical evaluation of the targeted great nail, marking whether or not they considered the nail to be clear of onychomycosis. This evaluation was the basis for determining whether or not study medication should be dispensed at the visit. This record includes information only for Cohort 3 (5% solution) of the study. Cohorts 1 and 2, are described in NCT00679523 (7.5% solution). No comparison was made between Cohorts 1&2 and Cohort 3.

Interventions

DRUGAN2690 Solution, 5.0%

Once daily application for 360 days

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

1. Subjects must meet all of the following criteria to be included in the study: 2. Witnessed, signed informed consent approved by Ethics Committee. 3. Male or female subjects of any race at least 18 years of age but not older than 65 years of age at the time of screening. 4. For Cohorts 1 and 2, subjects with a diagnosis of onychomycosis of at least one great toenail and with a positive KOH wet mount from that nail. For Cohort 3, subjects must have a diagnosis of onychomycosis of at least one great toenail and a positive KOH wet mount AND fungal culture from that nail. 5. Onychomycosis involving 20-60% of the affected great toenail as determined by visual inspection after the nail has been trimmed. 6. The combined thickness of the distal nail plate and the associated hyperkeratotic nail bed \<3 mm. 7. Affected great toenail to be treated is capable of re-growth as documented by history or recent observation of at least 2 mm of growth. 8. Normal or not clinically significant screening safety labs.

Exclusion criteria

1. Females of childbearing potential not using a highly effective method of birth control (e.g. implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices) during the study. 2. Diabetes mellitus requiring treatment other than diet and exercise. 3. Subjects with chronic moccasin type of T. pedis. 4. Subjects with a history of having failed any previous topical antifungal therapy for their onychomycosis. 5. Subjects unwilling to refrain from the use of nail cosmetics such as clear and or colored nail lacquers from the screening visit until the end of the study. 6. Subjects that have not undergone the specified washout period(s) for the following topical preparations or subjects who require the concurrent use of any of the following topical medications: * Topical antifungal applied to the feet (does not include antifungals for treatment of T. pedis during the study): 4 weeks * Anti-inflammatories, corticosteroids, topical immunomodulators: 2 weeks 7. Subjects that have not undergone the specified washout period(s) for the following systemic medications or subjects who require the concurrent use of any of the following systemic medications: * Corticosteroids (including intramuscular injections): 2 weeks * Antifungals for treatment of onychomycosis or any systemic antifungal with known activity against dermatophytes: 24 weeks * Systemic immunomodulators: 4 weeks 8. Treatment of any type for cancer within the last 6 months. 9. History of any significant internal disease. 10. Subjects with a medical history of current or past psoriasis of the skin and/or nails. 11. Concurrent lichen planus. 12. Subjects who are known to be allergic to any of the test product(s) or any components in the test product(s) or history of hypersensitivity or allergic reactions to any of the study preparations as described in the Investigator's Brochure. 13. Nail or anatomic abnormalities of the toe, e.g., genetic nail disorders, primentary disorders, onychogryphosis, trauma to the nail(s) to be treated. 14. AIDS or AIDS related complex. 15. History of street drug or alcohol abuse. 16. Any subject not able to meet the study attendance requirements. 17. Subjects who have participated in any other trial of an investigational drug or device within 60 days prior to enrollment or participation in a research study concurrent with this study.

Design outcomes

Primary

Measure	Time frame	Description
Clinical Evidence of Complete Clearance of the Treatment-targeted Great Toenail Plus a Negative Fungal Culture at Day 360	Day 360	Proportion of subjects with a clinical assessment of a clear (completely normal) nail unit plus a negative fungal culture from the treatment-targeted toenail at Day 360.

Secondary

Measure	Time frame	Description
Clear Nail Growth of the Targeted Toenail	Day 360	Clear nail was measured on digital images as the distance in millimeters from the proximal nail fold to the proximal limit of the disease as marked by the Investigator. New Clear Nail Growth (CNG) was calculated from the clear nail measurements.
Mycological Evaluations (Negative Potassium Hydroxide (KOH) and Negative Fungal Culture) Compared to Baseline	Day 90	Number of subjects with negative KOH, and number of subjects with negative fungal cultures.
Mycological Evaluations (Negative KOH and Negative Fungal Culture) Compared to Baseline	Day 180	Number of subjects with negative KOH, and number of subjects with negative fungal cultures.
Length of Time to Clinical Evaluation of Clear or at Least 5 mm of CNG	Baseline to 360	Length of time to clinical evaluation of clear or at least 5 mm of CNG.

Countries

Mexico

Participant flow

Recruitment details

Subjects were screened and enrolled and two investigative sites in Mexico. The study population included men and women of any race, 18-65 years of age who had distal, subungual onychomycosis of the great toenail. The first subject visit occurred on March 28, 2007, and the last subject visit occurred on July 11, 2008.

Pre-assignment details

All subjects in Cohort 3 were treated with 5.0% AN2690 Solution.

Participants by arm

Arm	Count
AN2690 Solution, 5.0% AN2690 Solution, 5.0%: Once daily application for 360 days	29
Total	29

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Lost to Follow-up	1

Baseline characteristics

Characteristic	AN2690 Solution, 5.0%
Age	46.9 years STANDARD_DEVIATION 10.15
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	29 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	29 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Region of Enrollment Mexico	29 participants
Sex: Female, Male Female	11 Participants
Sex: Female, Male Male	18 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	16 / 29
serious Total, serious adverse events	1 / 29

Outcome results

Primary

Clinical Evidence of Complete Clearance of the Treatment-targeted Great Toenail Plus a Negative Fungal Culture at Day 360

Proportion of subjects with a clinical assessment of a clear (completely normal) nail unit plus a negative fungal culture from the treatment-targeted toenail at Day 360.

Time frame: Day 360

Population: Efficacy data were analyzed for the ITT population. For efficacy variables, the last observation was carried forward (LOCF) to impute missing observations.

Arm	Measure	Group	Value (NUMBER)
AN2690 Solution, 5.0%	Clinical Evidence of Complete Clearance of the Treatment-targeted Great Toenail Plus a Negative Fungal Culture at Day 360	Success	2 participants
AN2690 Solution, 5.0%	Clinical Evidence of Complete Clearance of the Treatment-targeted Great Toenail Plus a Negative Fungal Culture at Day 360	Failure	27 participants

Secondary

Clear Nail Growth of the Targeted Toenail

Clear nail was measured on digital images as the distance in millimeters from the proximal nail fold to the proximal limit of the disease as marked by the Investigator. New Clear Nail Growth (CNG) was calculated from the clear nail measurements.

Time frame: Day 360