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

NCT01032382 | Completed Phase 2 Results

• 1 other identifier: PG-PERU-08-03, A-15809
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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).

Conditions

Leishmaniasis, Cutaneous

Keywords

leishmaniasis; cutaneous; WR 279,396; paromomycin; gentamicin; pharmacokinetics; safety; efficacy

Outcome Measures

Primary Outcomes (1)

• 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.

  Initial clinical cure by day 63 and no relapse by day 168

Secondary Outcomes (10)

• Detectable Paromomycin Plasma Levels

  Day 4, 7, 12, 17, 20, 28

• Paromomycin Plasma Concentrations in Children

  0 and 4 hours on days 1 and 20

• 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

• 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: 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

Study Arms (2)

Paromomycin Alone Treatment

ACTIVE COMPARATOR

Drug: Paromomycin Alone Cream (15% paromomycin topical cream)

WR 279,396

ACTIVE COMPARATOR

Drug: WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream)

Interventions

WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream) DRUG

topical application to CL lesions once daily for 20 days

Also known as: Topical paromomycin/gentimicin cream

WR 279,396

Paromomycin Alone Cream (15% paromomycin topical cream) DRUG

topical application to CL lesions once daily for 20 days

Paromomycin Alone Treatment

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible for the study, the following must be answered "YES" or not applicable, as appropriate for the study subject:
• Is the subject a male or female at least 5 years-of-age?
• Is the subject or legal guardian able to give written informed consent or assent, as appropriate?
• 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.
• Does the subject have at least one ulcerative lesion ≥ 1 cm and ≤ 5 cm, that meets the criteria for an index lesion?
• Is the subject willing to forego other forms of treatments for CL including other investigational treatments during the study?
• In the opinion of the investigator, is the subject (or their legal guardian) capable of understanding and complying with the protocol?
• 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?
• Does the subject have adequate venous access for blood draws?

You may not qualify if:

• To be eligible for the study, the following must be answered "NO" or not applicable as appropriate for the study subject:
• 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?
• 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?
• Does the subject have signs and symptoms of disseminated disease in the opinion of the Principal Investigator?
• Does the subject have \> 10 lesions?
• Is the subject a female who is breast-feeding?
• 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?
• 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?
• 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?
• Does the subject have a history of known or suspected hypersensitivity or idiosyncratic reactions to aminoglycosides?
• Does the subject have any other topical disease/condition which would interfere with the objectives of this study?

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead

Study Sites (1)

Universidad Peruana Cayetano Heredia (UPCH)

Lima, Peru

Location

Related Publications (1)

• Ravis WR, Llanos-Cuentas A, Sosa N, Kreishman-Deitrick M, Kopydlowski KM, Nielsen C, Smith KS, Smith PL, Ransom JH, Lin YJ, Grogl M. Pharmacokinetics and absorption of paromomycin and gentamicin from topical creams used to treat cutaneous leishmaniasis. Antimicrob Agents Chemother. 2013 Oct;57(10):4809-15. doi: 10.1128/AAC.00628-13. Epub 2013 Jul 22.

  PMID: 23877689 DERIVED

MeSH Terms

Conditions

Leishmaniasis, Cutaneous; Leishmaniasis

Interventions

Paromomycin

Condition Hierarchy (Ancestors)

Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Skin Diseases, Parasitic; Vector Borne Diseases; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Aminoglycosides; Glycosides; Carbohydrates

Limitations and Caveats

All randomized subjects were included in the mITT analysis. All subjects also met the criteria for the evaluable subset; therefore, no separate analysis of an evaluable subset of subjects was performed.

Results Point of Contact

• Title: Director, Division of Regulated Activites and Compliance
• Organization: US Army Medical Materiel Development Activity (USAMMDA)

usarmy.detrick.medcom-usammda.mbx.usamrmc-regulatory-affairs@mail.mil

301-619-0197

Study Officials

• Alejandro Llanos-Cuentas, M.D.

  Universidad Peruana Cayetano Heredia (UPCH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2009
• First Posted: December 15, 2009
• Study Start: January 1, 2010
• Primary Completion: March 1, 2011
• Study Completion: July 1, 2011
• Last Updated: July 16, 2015
• Results First Posted: August 22, 2014

Record last verified: 2014-08

Locations

PE (1)