Leishmaniasis, Cutaneous
Conditions
Keywords
leishmaniasis, cutaneous, WR 279,396, paromomycin, gentamicin, pharmacokinetics, safety, efficacy
Brief summary
The objectives of the study are to evaluate the pharmacokinetics (PK), safety, and efficacy of WR 279,396 (Paromomycin + Gentamicin Topical Cream) and Paromomycin Topical Cream in subjects with cutaneous leishmaniasis (CL).
Detailed description
This study is a single-site, randomized, double-blind, two group trial assessing the PK, safety and efficacy of WR 279,396 Topical Cream and Paromomycin Topical Cream in subjects with CL. Subjects will be screened over a period up to 28 days for eligibility including parasitology for confirmation of ulcerative CL. Subjects will be randomized in a targeted 1:1 ratio to receive either WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream) (target n=15) or Paromomycin Topical Cream (15% paromomycin topical cream) (target n=15) by topical application to CL lesions once daily for 20 days. Because the primary objective of this trial is to determine PK in all age groups, subjects will be stratified by age: 5-11 yrs, 12-17 yrs, and ≥ 18 yrs with at least 6 PK subjects in each age stratum and no more than 18 total subjects will be randomized in any age range. A target of 30 subjects who complete the PK part of the study is the goal. Any subject who does not complete the PK portion of the study will be replaced with another subject from the same age group that will be given the same treatment assignment to maintain the balance. Safety will be assessed by monitoring adverse events (AEs), lesion site reactions, vital signs, and blood creatinine levels. The primary efficacy analysis will be by evaluation of an index lesion with secondary efficacy analyses including all lesions. Lesions will also be examined for parasite negativity by classical means (positive culture for promastigotes or microscopic identification of amastigotes in stained lesion tissue) on Day 21. In adult subjects, on Days 1 and 20, blood will be collected prior to topical cream application and at 0.5h, 1h, 2h, 3h, and 4h ± 5 minutes and 8h, 12h, and 24h ± 15 minutes after completion of cream application to determine plasma levels of paromomycin and gentamicin to calculate PK parameters. Thus, the last blood draw in this series will occur on Day 21. In addition, blood will be collected on Days 4, 7, 12, and 17 ± 1 day before study drug application to examine trough plasma levels of paromomycin and gentamicin. A follow-up plasma sample for PK analysis will also be obtained on Day 28 ± 2 days. Subjects under the age of 18 years will have a total of four blood samples drawn. The first will be drawn at pre-application and the second will be drawn at 4 hours ± 5 minutes after completion of application of the topical cream on Study Day 1. The third will be drawn pre-application and the fourth at 4 hours ± 5 minutes after completion of application of the topical cream on Study Day 20. Subjects who receive Paromomycin Topical Cream are not expected to have blood levels of gentamicin, but as the study is blinded, plasma specimens will be tested for both paromomycin and gentamicin. The index lesion (primary ulcerated) and all other ulcerated lesions will be assessed for clinical response by measurement of the length and width of area of ulceration. A lesion will be considered to be completely cured if 100% re-epithelialization is observed (i.e., this is a measurement of ulceration of 0 x 0 mm). Non-ulcerated lesions will also be measured to monitor the total area of exposure of lesions to study drug and will be evaluated for cure (i.e., absence of signs of an active lesion). Subjects will have an in-clinic follow-up weekly (Days 28, 35, 42, 49, 56, and 63 ± 2 days) after completion of treatment for safety assessments, lesion measurements, and lesion photographs. On Day 21, index lesions in adult subjects that have not completely re-epithelialized will be assessed for parasites by classical means (positive culture for promastigotes or microscopic identification of amastigotes in stained lesion tissue). An interim analysis of all of the data collected on all subjects who were randomized and completed the nominal Day 63 follow-up will be performed to make decisions about the final design of a Phase 3 trial. Subjects will continue to be followed for outcomes at Day 100 and 168 ± 14 days. A final analysis of outcomes after the longer term followup period has been completed for all subjects will be performed when the trial is closed. Follow-up evaluations include AEs, medication use, lesion measurements, and lesion photographs. Patients who fail therapy (see definition of failure below) may be administered rescue therapy at the discretion of the patient's personal physician.
Interventions
topical application to CL lesions once daily for 20 days
topical application to CL lesions once daily for 20 days
Sponsors
U.S. Army Medical Research and Development Command
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
5 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* To be eligible for the study, the following must be answered YES or not applicable, as appropriate for the study subject: 1. Is the subject a male or female at least 5 years-of-age? 2. Is the subject or legal guardian able to give written informed consent or assent, as appropriate? 3. Does the subject have a diagnosis of CL in at least one lesion by at least one of the following methods: 1) positive culture for promastigotes, or 2) microscopic identification of amastigotes in stained lesion tissue. 4. Does the subject have at least one ulcerative lesion ≥ 1 cm and ≤ 5 cm, that meets the criteria for an index lesion? 5. Is the subject willing to forego other forms of treatments for CL including other investigational treatments during the study? 6. In the opinion of the investigator, is the subject (or their legal guardian) capable of understanding and complying with the protocol? 7. If female and of child-bearing potential, did the subject have a negative pregnancy test during screening and agree to use an acceptable method of birth control during the treatment phase and for 1 month after treatment is completed? 8. Does the subject have adequate venous access for blood draws?
Exclusion criteria
To be eligible for the study, the following must be answered NO or not applicable as appropriate for the study subject: 1. Does the subject have only a single lesion whose characteristics include any of the following: verrucous or nodular lesion (non-ulcerative), lesion \<1 cm in its greatest diameter, lesion in a location that in the opinion of the Investigator is difficult to maintain application of study drugs topically? 2. Does the subject have a lesion due to leishmania that involves the mucosa or palate or any signs of mucosal disease that might be due to leishmania? 3. Does the subject have signs and symptoms of disseminated disease in the opinion of the Principal Investigator? 4. Does the subject have \> 10 lesions? 5. Is the subject a female who is breast-feeding? 6. Does the subject have an active malignancy or history of solid, metastatic or hematologic malignancy with the exception of basal or squamous cell carcinoma of the skin that has been removed? 7. Does the subject have significant organ abnormality, chronic disease such as diabetes, severe hearing loss, evidence of renal or hepatic dysfunction, or creatinine greater than 15%, or aspartate aminotransferase (AST), or alanine aminotransferase (ALT) greater than 1.5 times the above the upper limit of normal (ULN) as defined by the clinical laboratory defined normal ranges? 8. Has the subject received treatment for leishmaniasis including any medication with pentavalent antimony including sodium stibogluconate (Pentostam), meglumine antimoniate (Glucantime); amphotericin B (including liposomal amphotericin B and amphotericin B deoxycholate); or other medications containing paromomycin (administered parenterally or topically) or methylbenzethonium chloride (MBCL); gentamicin; fluconazole; ketoconazole; pentamidine; miltefosine, azithromycin or allopurinol that was completed within 8 weeks of starting study treatments? 9. Does the subject have a history of known or suspected hypersensitivity or idiosyncratic reactions to aminoglycosides? 10. Does the subject have any other topical disease/condition which would interfere with the objectives of this study?
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Final Clinical Cure for Index Lesions | Initial clinical cure by day 63 and no relapse by day 168 | Final clinical cure was defined as follows: 1. Subject has initial clinical cure (100% re-epithelialization of index lesion by nominal Day 63); OR, 2. Subject has initial clinical improvement (\> 50% re-epithelialization of index lesion by nominal Day 63 followed by 100% re-epithelialization of the index lesion on or before nominal Day 100; AND, 3. Subject has no relapse of index lesion by Day 168. Relapse was defined as an index lesion meeting the criteria for initial clinical cure that had any new ulceration/nodule (\> 0 x 0 mm measurement) by nominal day 168, or an index lesion meeting the criteria for initial clinical improvement that subsequently enlarged by nominal Day 168. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Paromomycin Plasma Concentrations in Children | 0 and 4 hours on days 1 and 20 | Paromomycin plasma concentrations 4 hours following administration of paromomycin alone or WR 279,396 in children |
| Pharmacokinetic Parameter: Cmax | 0, 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, 12.0, 24.0 hours on both Days 1 and 20 | Cmax of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama |
| Pharmacokinetic Parameter: Tmax | 0, 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, 12.0, 24.0 hours on both Days 1 and 20 | Pharmacokinetic Parameter: Tmax |
| Pharmacokinetic Parameter: Area Under the Curve (AUC) | 0, 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, 12.0, 24.0 hours on both Days 1 and 20 | Area under the curve (AUC) of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama |
| Detectable Paromomycin Plasma Levels | Day 4, 7, 12, 17, 20, 28 | Paromomycin plasma concentrations following administration of paromomycin alone or WR 279,396 in adults |
| Pharmacokinetic Parameter: Cmax/D | 0, 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, 12.0, 24.0 hours on both Days 1 and 20 | Maximum observed plasma concentration divide by topical dose (Cmax/D) of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama |
| Pharmacokinetic Parameter: AUC/D | Days 1 and 20 | Area under the plasma concentration-time curve over 24 hrs divided by topical dose (AUC/D) of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama |
| Final Clinical Cure on All Lesions Independent of Subjects | Initial clinical cure by day 63 and no relapse by day 168 | Final clinical cure was defined as follows: 1. Subject has initial clinical cure (100% re-epithelialization of lesion by nominal Day 63); OR, 2. Subject has initial clinical improvement (\> 50% re-epithelialization of lesion by nominal Day 63 followed by 100% re-epithelialization of the lesion on or before nominal Day 100; AND, 3. Subject has no relapse of lesion by Day 168. Relapse was defined as a lesion meeting the criteria for initial clinical cure that had any new ulceration/nodule (\> 0 x 0 mm measurement) by nominal day 168, or a lesion meeting the criteria for initial clinical improvement that subsequently enlarged by nominal Day 168. |
| Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 1, 4, 7, 12, 17, 20, 28, 35, 42, 49, 56, 63, 100, 168 | Number of study participants who meet the criteria for clinical cure (100% re-epithelialization) at specified timepoints during the study. |
| Pharmacokinetic Parameter: t(1/2) | 0, 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, 12.0, 24.0 hours on both Days 1 and 20 | t(1/2) of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama |
Countries
Peru
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Paromomycin Alone Treatment Paromomycin Alone Cream (15% paromomycin topical cream): topical application to CL lesions once daily for 20 days | 16 |
| WR 279,396 WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream): topical application to CL lesions once daily for 20 days | 14 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Disease dissemination | 1 | 1 |
| Overall Study | Index lesion relapse | 1 | 3 |
| Overall Study | Treatment failure | 3 | 1 |
Baseline characteristics
| Characteristic | Paromomycin Alone Treatment | WR 279,396 | Total |
|---|---|---|---|
| Age, Continuous | 20.7 years STANDARD_DEVIATION 16.2 | 18.2 years STANDARD_DEVIATION 15.1 | 19.5 years STANDARD_DEVIATION 15.5 |
| Age, Customized Adults (18+ years) | 5 participants | 4 participants | 9 participants |
| Age, Customized Children (12 to 17 years) | 5 participants | 3 participants | 8 participants |
| Age, Customized Children (5 to 11 years) | 6 participants | 7 participants | 13 participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 11 Participants | 10 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 16 | 14 / 14 |
| serious Total, serious adverse events | 0 / 16 | 0 / 14 |
Outcome results
Primary
Final Clinical Cure for Index Lesions
Final clinical cure was defined as follows: 1. Subject has initial clinical cure (100% re-epithelialization of index lesion by nominal Day 63); OR, 2. Subject has initial clinical improvement (\> 50% re-epithelialization of index lesion by nominal Day 63 followed by 100% re-epithelialization of the index lesion on or before nominal Day 100; AND, 3. Subject has no relapse of index lesion by Day 168. Relapse was defined as an index lesion meeting the criteria for initial clinical cure that had any new ulceration/nodule (\> 0 x 0 mm measurement) by nominal day 168, or an index lesion meeting the criteria for initial clinical improvement that subsequently enlarged by nominal Day 168.
Time frame: Initial clinical cure by day 63 and no relapse by day 168
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paromomycin Alone Treatment | Final Clinical Cure for Index Lesions | 11 participants |
| WR 279,396 | Final Clinical Cure for Index Lesions | 9 participants |
Secondary
Detectable Paromomycin Plasma Levels
Paromomycin plasma concentrations following administration of paromomycin alone or WR 279,396 in adults
Time frame: Day 4, 7, 12, 17, 20, 28
Population: Adults (18+ years)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paromomycin Alone Treatment | Detectable Paromomycin Plasma Levels | Day 17 | 210.0 ng/mL | Standard Deviation 327 |
| Paromomycin Alone Treatment | Detectable Paromomycin Plasma Levels | Day 7 | 10.3 ng/mL | Standard Deviation 23.1 |
| Paromomycin Alone Treatment | Detectable Paromomycin Plasma Levels | Day 20 | 87.3 ng/mL | Standard Deviation 109 |
| Paromomycin Alone Treatment | Detectable Paromomycin Plasma Levels | Day 12 | 36.2 ng/mL | Standard Deviation 33.2 |
| Paromomycin Alone Treatment | Detectable Paromomycin Plasma Levels | Day 28 | 0 ng/mL | Standard Deviation 0 |
| Paromomycin Alone Treatment | Detectable Paromomycin Plasma Levels | Day 4 | 12.1 ng/mL | Standard Deviation 27 |
| WR 279,396 | Detectable Paromomycin Plasma Levels | Day 28 | 0 ng/mL | Standard Deviation 0 |
| WR 279,396 | Detectable Paromomycin Plasma Levels | Day 4 | 37.3 ng/mL | Standard Deviation 74.5 |
| WR 279,396 | Detectable Paromomycin Plasma Levels | Day 12 | 78.9 ng/mL | Standard Deviation 81.6 |
| WR 279,396 | Detectable Paromomycin Plasma Levels | Day 17 | 162.0 ng/mL | Standard Deviation 123 |
| WR 279,396 | Detectable Paromomycin Plasma Levels | Day 20 | 128.0 ng/mL | Standard Deviation 58.7 |
| WR 279,396 | Detectable Paromomycin Plasma Levels | Day 7 | 17.9 ng/mL | Standard Deviation 35.8 |
Secondary
Final Clinical Cure on All Lesions Independent of Subjects
Final clinical cure was defined as follows: 1. Subject has initial clinical cure (100% re-epithelialization of lesion by nominal Day 63); OR, 2. Subject has initial clinical improvement (\> 50% re-epithelialization of lesion by nominal Day 63 followed by 100% re-epithelialization of the lesion on or before nominal Day 100; AND, 3. Subject has no relapse of lesion by Day 168. Relapse was defined as a lesion meeting the criteria for initial clinical cure that had any new ulceration/nodule (\> 0 x 0 mm measurement) by nominal day 168, or a lesion meeting the criteria for initial clinical improvement that subsequently enlarged by nominal Day 168.
Time frame: Initial clinical cure by day 63 and no relapse by day 168
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paromomycin Alone Treatment | Final Clinical Cure on All Lesions Independent of Subjects | 12 Cured ulcerated lesions |
| WR 279,396 | Final Clinical Cure on All Lesions Independent of Subjects | 14 Cured ulcerated lesions |
Secondary
Number of Index Lesions Meeting Criteria for Clinical Cure During the Study
Number of study participants who meet the criteria for clinical cure (100% re-epithelialization) at specified timepoints during the study.
Time frame: Day 1, 4, 7, 12, 17, 20, 28, 35, 42, 49, 56, 63, 100, 168
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paromomycin Alone Treatment | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 1 | 0 Lesions meeting clinical cure criteria |
| Paromomycin Alone Treatment | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 4 | 0 Lesions meeting clinical cure criteria |
| Paromomycin Alone Treatment | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 7 | 0 Lesions meeting clinical cure criteria |
| Paromomycin Alone Treatment | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 12 | 0 Lesions meeting clinical cure criteria |
| Paromomycin Alone Treatment | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 17 | 0 Lesions meeting clinical cure criteria |
| Paromomycin Alone Treatment | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 20 | 1 Lesions meeting clinical cure criteria |
| Paromomycin Alone Treatment | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 28 | 5 Lesions meeting clinical cure criteria |
| Paromomycin Alone Treatment | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 35 | 8 Lesions meeting clinical cure criteria |
| Paromomycin Alone Treatment | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 42 | 10 Lesions meeting clinical cure criteria |
| Paromomycin Alone Treatment | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 49 | 10 Lesions meeting clinical cure criteria |
| Paromomycin Alone Treatment | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 56 | 11 Lesions meeting clinical cure criteria |
| Paromomycin Alone Treatment | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 63 | 11 Lesions meeting clinical cure criteria |
| Paromomycin Alone Treatment | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 100 | 12 Lesions meeting clinical cure criteria |
| Paromomycin Alone Treatment | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 168 | 11 Lesions meeting clinical cure criteria |
| WR 279,396 | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 56 | 10 Lesions meeting clinical cure criteria |
| WR 279,396 | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 1 | 0 Lesions meeting clinical cure criteria |
| WR 279,396 | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 35 | 11 Lesions meeting clinical cure criteria |
| WR 279,396 | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 4 | 0 Lesions meeting clinical cure criteria |
| WR 279,396 | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 100 | 10 Lesions meeting clinical cure criteria |
| WR 279,396 | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 7 | 0 Lesions meeting clinical cure criteria |
| WR 279,396 | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 42 | 11 Lesions meeting clinical cure criteria |
| WR 279,396 | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 12 | 0 Lesions meeting clinical cure criteria |
| WR 279,396 | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 63 | 10 Lesions meeting clinical cure criteria |
| WR 279,396 | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 17 | 0 Lesions meeting clinical cure criteria |
| WR 279,396 | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 49 | 12 Lesions meeting clinical cure criteria |
| WR 279,396 | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 20 | 0 Lesions meeting clinical cure criteria |
| WR 279,396 | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 168 | 9 Lesions meeting clinical cure criteria |
| WR 279,396 | Number of Index Lesions Meeting Criteria for Clinical Cure During the Study | Day 28 | 6 Lesions meeting clinical cure criteria |
Secondary
Paromomycin Plasma Concentrations in Children
Paromomycin plasma concentrations 4 hours following administration of paromomycin alone or WR 279,396 in children
Time frame: 0 and 4 hours on days 1 and 20
Population: Children ages 5 to 17 (inclusive)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paromomycin Alone Treatment | Paromomycin Plasma Concentrations in Children | Day 1 hour 0 | 6.2 ng/mL | Standard Deviation 20.5 |
| Paromomycin Alone Treatment | Paromomycin Plasma Concentrations in Children | Day 1 hour 4 | 71.2 ng/mL | Standard Deviation 88 |
| Paromomycin Alone Treatment | Paromomycin Plasma Concentrations in Children | Day 20 hour 0 | 93.8 ng/mL | Standard Deviation 59.9 |
| Paromomycin Alone Treatment | Paromomycin Plasma Concentrations in Children | Day 20 hour 4 | 744.0 ng/mL | Standard Deviation 503 |
| WR 279,396 | Paromomycin Plasma Concentrations in Children | Day 20 hour 4 | 1030.0 ng/mL | Standard Deviation 1460 |
| WR 279,396 | Paromomycin Plasma Concentrations in Children | Day 1 hour 0 | 22.1 ng/mL | Standard Deviation 69.9 |
| WR 279,396 | Paromomycin Plasma Concentrations in Children | Day 20 hour 0 | 89.2 ng/mL | Standard Deviation 132 |
| WR 279,396 | Paromomycin Plasma Concentrations in Children | Day 1 hour 4 | 322.0 ng/mL | Standard Deviation 757 |
Secondary
Pharmacokinetic Parameter: Area Under the Curve (AUC)
Area under the curve (AUC) of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama
Time frame: 0, 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, 12.0, 24.0 hours on both Days 1 and 20
Population: Adults (18+ years)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paromomycin Alone Treatment | Pharmacokinetic Parameter: Area Under the Curve (AUC) | Day 1 | 3154 ng*hr/mL | Standard Deviation 3562 |
| Paromomycin Alone Treatment | Pharmacokinetic Parameter: Area Under the Curve (AUC) | Day 20 | 13331 ng*hr/mL | Standard Deviation 9156 |
| WR 279,396 | Pharmacokinetic Parameter: Area Under the Curve (AUC) | Day 1 | 1228 ng*hr/mL | Standard Deviation 1413 |
| WR 279,396 | Pharmacokinetic Parameter: Area Under the Curve (AUC) | Day 20 | 8955 ng*hr/mL | Standard Deviation 1955 |
Secondary
Pharmacokinetic Parameter: AUC/D
Area under the plasma concentration-time curve over 24 hrs divided by topical dose (AUC/D) of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama
Time frame: Days 1 and 20
Population: Adults (18+ years)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paromomycin Alone Treatment | Pharmacokinetic Parameter: AUC/D | Day 1 | 996.7 hr/ML | Standard Deviation 976.1 |
| Paromomycin Alone Treatment | Pharmacokinetic Parameter: AUC/D | Day 20 | 3335 hr/ML | Standard Deviation 1482 |
| WR 279,396 | Pharmacokinetic Parameter: AUC/D | Day 1 | 340.5 hr/ML | Standard Deviation 368.9 |
| WR 279,396 | Pharmacokinetic Parameter: AUC/D | Day 20 | 3155 hr/ML | Standard Deviation 2151 |
Secondary
Pharmacokinetic Parameter: Cmax
Cmax of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama
Time frame: 0, 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, 12.0, 24.0 hours on both Days 1 and 20
Population: Adults (18+ years)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paromomycin Alone Treatment | Pharmacokinetic Parameter: Cmax | Day 1 | 511 ng/mL | Standard Deviation 445 |
| Paromomycin Alone Treatment | Pharmacokinetic Parameter: Cmax | Day 20 | 1400 ng/mL | Standard Deviation 842 |
| WR 279,396 | Pharmacokinetic Parameter: Cmax | Day 1 | 155.0 ng/mL | Standard Deviation 139 |
| WR 279,396 | Pharmacokinetic Parameter: Cmax | Day 20 | 882 ng/mL | Standard Deviation 124 |
Secondary
Pharmacokinetic Parameter: Cmax/D
Maximum observed plasma concentration divide by topical dose (Cmax/D) of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama
Time frame: 0, 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, 12.0, 24.0 hours on both Days 1 and 20
Population: Adults (18+ years)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paromomycin Alone Treatment | Pharmacokinetic Parameter: Cmax/D | Day 1 | 185 1/ML | Standard Deviation 144 |
| Paromomycin Alone Treatment | Pharmacokinetic Parameter: Cmax/D | Day 20 | 368 1/ML | Standard Deviation 196 |
| WR 279,396 | Pharmacokinetic Parameter: Cmax/D | Day 1 | 45.9 1/ML | Standard Deviation 35.8 |
| WR 279,396 | Pharmacokinetic Parameter: Cmax/D | Day 20 | 283 1/ML | Standard Deviation 118 |
Secondary
Pharmacokinetic Parameter: t(1/2)
t(1/2) of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama
Time frame: 0, 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, 12.0, 24.0 hours on both Days 1 and 20
Population: Adults (18+ years). WR 279,396 group measurements Day 1 N = 2 and Day 20 N = 4. One study participant in the Paromomycin Alone Treatment was withdrawn at Day 100.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paromomycin Alone Treatment | Pharmacokinetic Parameter: t(1/2) | Day 1 | 2.55 hr | Standard Deviation 1.23 |
| Paromomycin Alone Treatment | Pharmacokinetic Parameter: t(1/2) | Day 20 | 7.17 hr | Standard Deviation 3.29 |
| WR 279,396 | Pharmacokinetic Parameter: t(1/2) | Day 20 | 6.81 hr | Standard Deviation 3.2 |
| WR 279,396 | Pharmacokinetic Parameter: t(1/2) | Day 1 | 4.51 hr | Standard Deviation 0.06 |
Secondary
Pharmacokinetic Parameter: Tmax
Pharmacokinetic Parameter: Tmax
Time frame: 0, 0.5, 1.0, 2.0, 3.0, 4.0, 8.0, 12.0, 24.0 hours on both Days 1 and 20
Population: Adults (18+ years). On day 1, Paromomycin Alone Treatment group N = 4; WR 279,396 group N = 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paromomycin Alone Treatment | Pharmacokinetic Parameter: Tmax | Day 1 | 2.25 hr | Standard Deviation 0.5 |
| Paromomycin Alone Treatment | Pharmacokinetic Parameter: Tmax | Day 20 | 4.6 hr | Standard Deviation 3.13 |
| WR 279,396 | Pharmacokinetic Parameter: Tmax | Day 1 | 3 hr | Standard Deviation 1.73 |
| WR 279,396 | Pharmacokinetic Parameter: Tmax | Day 20 | 3 hr | Standard Deviation 1.15 |