Tinea Pedis, Tinea Cruris
Conditions
Brief summary
This is an open-label, maximal use study to evaluate whether luliconazole in plasma acts as an inhibitor of cytochrome P2C19 (CYP2C19) as measured by circulating levels of omeprazole before and after treatment with a maximum dose of luliconazole cream 1% in participants with moderate to severe tinea pedis and tinea cruris.
Interventions
DRUGOmeprazole 40 mg
Oral capsule to be taken as per the instructions regarding proper dosing technique.
Topical cream to be applied as per the instructions regarding proper study drug application technique.
Sponsors
Bausch Health Americas, Inc.
Bausch & Lomb Incorporated
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with a clinical diagnosis of moderate to severe interdigital tinea pedis, as defined by a Physician's Global Assessment (PGA) score of 2 or 3 on both feet, and moderate to severe tinea cruris, as defined by a PGA score of 2 or 3 * Participants with a mycological diagnosis of tinea pedis and tinea cruris confirmed by the detection of fungal hyphae on a microscopic potassium hydroxide (KOH) wet mount * Participants must be in good general health and free of any disease that might interfere with study evaluations * Participants with the ability and willingness to follow all study procedures, attend all scheduled visits, and successfully complete the study
Exclusion criteria
* Female participants who are pregnant and/or nursing or planning a pregnancy during the course of the trial * Participants who are immunocompromised * Participants who have a recent history of or currently known drug or alcohol abuse * Participants with a history of intolerance or hypersensitivity to imidazole compounds, proton pump inhibitors, or the inactive components of luliconazole cream 1% or omeprazole * Participants with a life-threatening condition within the last 6 months * Participants with uncontrolled diabetes mellitus * Participants who are unable to communicate or cooperate with the Investigator * Participants using medications for treatment of tinea pedis and/or tinea cruris (see Investigator for length of time prior to study start) * Participants receiving concomitant drugs that are known to inhibit and/or induce CYP2C19 and/or CYP3A4, or that interact with omeprazole * Because of the potential for drug interaction with luliconazole, administration with medications that are known to be substrates of CYP3A4, CYP2B6, CYP2C8, and CYP2C19 should be carefully monitored
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Circulating Levels (Plasma Concentration) of Omeprazole Prior to Treatment With Luliconazole Cream 1% | 15 minutes predose; 15, 30, 45, and 60 minutes postdose; and 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 24 hours postdose of omeprazole on Day 1 | Circulating plasma levels of omeprazole were measured using validated liquid chromatography with tandem mass spectrometry detection (LS/MS-MS) methods. The range for omeprazole determination was 4.64-9.27 nanograms/milliliter (ng/mL). Serial blood sampling occurred in each enrolled participant up to 24 hours post treatment (Day 1) with omeprazole (before the start of luliconazole cream 1% treatment on Day 2). |
| Circulating Levels (Plasma Concentration) of Omeprazole After 1 Week of Treatment With Luliconazole Cream 1% | 15 minutes predose; 15, 30, 45, and 60 minutes postdose; and 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 24 hours postdose of omeprazole on Day 8 | Circulating plasma levels of omeprazole were measured using validated LS/MS-MS methods. The range for omeprazole determination was 4.64-9.27 ng/mL. Serial blood sampling occurred in each enrolled participant up to 24 hours post treatment (Day 8) with omeprazole (after using luliconazole cream 1% treatment for 1 week). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Luliconazole Cream 1% Participants received 1 oral capsule of omeprazole 40 mg on Day 1 and Day 8. Participants also received luliconazole cream 1% to cover the entire affected surface areas and adjacent areas once daily in the morning on Day 2 (24 hours after initial omeprazole dosing) through Day 8. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Failed drug screen test | 1 |
Baseline characteristics
| Characteristic | Luliconazole Cream 1% |
|---|---|
| Age, Continuous | 45.05 years STANDARD_DEVIATION 10.47 |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Circulating Levels (Plasma Concentration) of Omeprazole After 1 Week of Treatment With Luliconazole Cream 1%
Circulating plasma levels of omeprazole were measured using validated LS/MS-MS methods. The range for omeprazole determination was 4.64-9.27 ng/mL. Serial blood sampling occurred in each enrolled participant up to 24 hours post treatment (Day 8) with omeprazole (after using luliconazole cream 1% treatment for 1 week).
Time frame: 15 minutes predose; 15, 30, 45, and 60 minutes postdose; and 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 24 hours postdose of omeprazole on Day 8
Population: Randomized participants who received at least 1 dose of study drug and had evaluable data at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole After 1 Week of Treatment With Luliconazole Cream 1% | Predose | 0 ng/mL | Standard Deviation 0 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole After 1 Week of Treatment With Luliconazole Cream 1% | 15 minutes postdose | 0 ng/mL | Standard Deviation 0 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole After 1 Week of Treatment With Luliconazole Cream 1% | 30 minutes postdose | 18.11 ng/mL | Standard Deviation 68.24 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole After 1 Week of Treatment With Luliconazole Cream 1% | 45 minutes postdose | 142.72 ng/mL | Standard Deviation 298.29 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole After 1 Week of Treatment With Luliconazole Cream 1% | 1 hour postdose | 317.21 ng/mL | Standard Deviation 401.97 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole After 1 Week of Treatment With Luliconazole Cream 1% | 1.5 hours postdose | 637.56 ng/mL | Standard Deviation 509.09 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole After 1 Week of Treatment With Luliconazole Cream 1% | 2 hours postdose | 763.51 ng/mL | Standard Deviation 607.8 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole After 1 Week of Treatment With Luliconazole Cream 1% | 2.5 hours postdose | 700.91 ng/mL | Standard Deviation 423.74 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole After 1 Week of Treatment With Luliconazole Cream 1% | 3 hours postdose | 730.56 ng/mL | Standard Deviation 349.1 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole After 1 Week of Treatment With Luliconazole Cream 1% | 4 hours postdose | 586.83 ng/mL | Standard Deviation 309.83 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole After 1 Week of Treatment With Luliconazole Cream 1% | 6 hours postdose | 323.40 ng/mL | Standard Deviation 219.5 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole After 1 Week of Treatment With Luliconazole Cream 1% | 8 hours postdose | 190.15 ng/mL | Standard Deviation 154.82 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole After 1 Week of Treatment With Luliconazole Cream 1% | 10 hours postdose | 111.51 ng/mL | Standard Deviation 102.3 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole After 1 Week of Treatment With Luliconazole Cream 1% | 24 hours postdose | 6.84 ng/mL | Standard Deviation 10.01 |
Primary
Circulating Levels (Plasma Concentration) of Omeprazole Prior to Treatment With Luliconazole Cream 1%
Circulating plasma levels of omeprazole were measured using validated liquid chromatography with tandem mass spectrometry detection (LS/MS-MS) methods. The range for omeprazole determination was 4.64-9.27 nanograms/milliliter (ng/mL). Serial blood sampling occurred in each enrolled participant up to 24 hours post treatment (Day 1) with omeprazole (before the start of luliconazole cream 1% treatment on Day 2).
Time frame: 15 minutes predose; 15, 30, 45, and 60 minutes postdose; and 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 24 hours postdose of omeprazole on Day 1
Population: Randomized participants who received at least 1 dose of study drug and had evaluable data at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole Prior to Treatment With Luliconazole Cream 1% | Predose | 0 ng/mL | Standard Deviation 0 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole Prior to Treatment With Luliconazole Cream 1% | 15 minutes postdose | 0 ng/mL | Standard Deviation 0 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole Prior to Treatment With Luliconazole Cream 1% | 30 minutes postdose | 23.67 ng/mL | Standard Deviation 89.46 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole Prior to Treatment With Luliconazole Cream 1% | 45 minutes postdose | 196.30 ng/mL | Standard Deviation 301.31 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole Prior to Treatment With Luliconazole Cream 1% | 1 hour postdose | 463.74 ng/mL | Standard Deviation 546.51 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole Prior to Treatment With Luliconazole Cream 1% | 1.5 hours postdose | 526.98 ng/mL | Standard Deviation 499.6 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole Prior to Treatment With Luliconazole Cream 1% | 2 hours postdose | 655.70 ng/mL | Standard Deviation 520.31 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole Prior to Treatment With Luliconazole Cream 1% | 2.5 hours postdose | 621.08 ng/mL | Standard Deviation 464.55 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole Prior to Treatment With Luliconazole Cream 1% | 3 hours postdose | 636.60 ng/mL | Standard Deviation 508.53 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole Prior to Treatment With Luliconazole Cream 1% | 4 hours postdose | 468.79 ng/mL | Standard Deviation 355.49 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole Prior to Treatment With Luliconazole Cream 1% | 6 hours postdose | 235.20 ng/mL | Standard Deviation 214.29 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole Prior to Treatment With Luliconazole Cream 1% | 8 hours postdose | 129.70 ng/mL | Standard Deviation 129.08 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole Prior to Treatment With Luliconazole Cream 1% | 10 hours postdose | 74.24 ng/mL | Standard Deviation 84.54 |
| Luliconazole Cream 1% | Circulating Levels (Plasma Concentration) of Omeprazole Prior to Treatment With Luliconazole Cream 1% | 24 hours postdose | 3.32 ng/mL | Standard Deviation 6.18 |