Safety, Efficacy and Pharmacokinetics (PK) Study of WR 279,396 Versus Paromomycin for Treatment of Cutaneous Leishmaniasis (Peru-PK)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:
NCT01032382
First received: December 14, 2009
Last updated: August 6, 2014
Last verified: August 2014
  Purpose

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).


Condition Intervention Phase
Leishmaniasis, Cutaneous
Drug: WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream)
Drug: Paromomycin Alone Cream (15% paromomycin topical cream)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Double-blind, Randomized, Pharmacokinetics, Safety, and Efficacy Trial of WR 279,396 (Paromomycin + Gentamicin Topical Cream) and Paromomycin Topical Cream for the Treatment of Cutaneous Leishmaniasis in Peru

Resource links provided by NLM:


Further study details as provided by U.S. Army Medical Research and Materiel Command:

Primary Outcome Measures:
  • Final Clinical Cure for Index Lesions [ Time Frame: Initial clinical cure by day 63 and no relapse by day 168 ] [ Designated as safety issue: No ]

    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 Outcome Measures:
  • Detectable Paromomycin Plasma Levels [ Time Frame: Day 4, 7, 12, 17, 20, 28 ] [ Designated as safety issue: No ]
    Paromomycin plasma concentrations following administration of paromomycin alone or WR 279,396 in adults

  • Paromomycin Plasma Concentrations in Children [ Time Frame: 0 and 4 hours on days 1 and 20 ] [ Designated as safety issue: No ]
    Paromomycin plasma concentrations 4 hours following administration of paromomycin alone or WR 279,396 in children

  • Pharmacokinetic Parameter: Cmax [ 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 ] [ Designated as safety issue: No ]
    Cmax of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama

  • 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 ] [ Designated as safety issue: No ]
    Pharmacokinetic Parameter: Tmax

  • Pharmacokinetic Parameter: Area Under the Curve (AUC) [ 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 ] [ Designated as safety issue: No ]
    Area under the curve (AUC) of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama

  • Pharmacokinetic Parameter: t(1/2) [ 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 ] [ Designated as safety issue: No ]
    t(1/2) of paromomycin following administration of paromomycin alone or WR 279,396 to adults in Panama

  • Pharmacokinetic Parameter: Cmax/D [ 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 1 and 20 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Initial clinical cure by day 63 and no relapse by day 168 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 1, 4, 7, 12, 17, 20, 28, 35, 42, 49, 56, 63, 100, 168 ] [ Designated as safety issue: No ]
    Number of study participants who meet the criteria for clinical cure (100% re-epithelialization) at specified timepoints during the study.


Enrollment: 30
Study Start Date: January 2010
Study Completion Date: July 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Paromomycin Alone Treatment Drug: Paromomycin Alone Cream (15% paromomycin topical cream)
topical application to CL lesions once daily for 20 days
Active Comparator: WR 279,396 Drug: WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream)
topical application to CL lesions once daily for 20 days
Other Name: Topical paromomycin/gentimicin cream

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   5 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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?
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01032382

Locations
Peru
Universidad Peruana Cayetano Heredia (UPCH)
Lima, Peru
Sponsors and Collaborators
U.S. Army Medical Research and Materiel Command
Investigators
Principal Investigator: Alejandro Llanos-Cuentas, M.D. Universidad Peruana Cayetano Heredia (UPCH)
  More Information

No publications provided by U.S. Army Medical Research and Materiel Command

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT01032382     History of Changes
Other Study ID Numbers: PG-PERU-08-03, A-15809
Study First Received: December 14, 2009
Results First Received: June 6, 2014
Last Updated: August 6, 2014
Health Authority: United States: Food and Drug Administration
Peru: Ethics Committee
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Peru: Instituto Nacional de Salud
Peru: Ministry of Health

Keywords provided by U.S. Army Medical Research and Materiel Command:
leishmaniasis
cutaneous
WR 279,396
paromomycin
gentamicin
pharmacokinetics
safety
efficacy

Additional relevant MeSH terms:
Leishmaniasis
Leishmaniasis, Cutaneous
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Skin Diseases, Parasitic
Skin Diseases, Infectious
Skin Diseases
Gentamicins
Paromomycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Amebicides
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on August 28, 2014