A Study Evaluating Sitamaquine Compared With Amphotericin B In The Treatment Of Visceral Leishmaniasis.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00381394
First received: September 26, 2006
Last updated: May 31, 2012
Last verified: February 2011
  Purpose

Sitamaquine is an 8-aminoquinoline which is being developed as an oral treatment for visceral leishmaniasis (VL). Pre-clinical and subsequent clinical investigations have demonstrated oral efficacy against Leishmania donovani. The purposes of this study are to characterise the pharmacokinetic profile of sitamaquine, administered orally, and to determine if the pharmacokinetic profile is affected by administration with food. The study is also designed to further characterise the safety and tolerability of sitamaquine compared with amphotericin B, particularly in reference to renal, hepatic and cardiac adverse events, prior to initiation of phase III studies. Finally the study will investigate the efficacy of a 21 day treatment course. Previous studies have used 28 days dosing, but parasitological evidence from one study suggests that shorter courses may be effective.


Condition Intervention Phase
Visceral Leishmaniasis
Leishmaniasis, Visceral
Drug: sitamaquine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Multi-centre, Open-label, Randomised Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Oral Sitamaquine Compared With Amphotericin B in the Treatment of Visceral Leishmaniasis Caused by L. Donovani in Endemic Areas.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • AUC(0-) Cmax time to maximum concentration (tmax)accumulation ratio for sitamaquine.

Secondary Outcome Measures:
  • 1. Safety parameters; adverse events, 12-lead ECG, echocardiography, vital signs, safety laboratory parameters 2. Initial parasitological cure (28 days) 3. Final parasitological cure (6 months) 4. PK parameter terminal half-life (t1/2) for sitamaquine

Estimated Enrollment: 60
Study Start Date: August 2006
Intervention Details:
    Drug: sitamaquine
    Other Name: sitamaquine
  Eligibility

Ages Eligible for Study:   16 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Clinical diagnosis of visceral leishmaniasis; symptoms and signs compatible with VL and diagnosis confirmed by visualisation of amastigotes in splenic aspirate or bone marrow.
  • Written informed consent or witnessed oral consent.
  • Willing to comply with the study visits and procedures.
  • For female subjects, a negative urine pregnancy test at screening and before dosing and the subject agrees to use an established method of birth control (including abstinence).

Exclusion criteria:

  • Past history of renal disease or impaired renal function at screening.
  • History of any significant hepatic or biliary disease, or the following abnormal laboratory values at screening; hepatic dysfunction (AST or ALT 2.5 times upper limit of normal).
  • Subjects with the following abnormal laboratory values; haemoglobin 6.5 g/dl, neutrophils <750/ mm3, platelets <50,000 / mm3, any clinically relevant abnormality identified on screening examination or clinical laboratories which would preclude the subject's safe participation in the study.
  • History of cardiac disease, arrhythmias, conduction abnormalities or any clinically relevant abnormality identified on 12-lead ECG at screening.

Subjects suffering from a concomitant infection, blood disorder or any other serious underlying disease which would preclude evaluation of the subject's response to the study medication.

Methaemoglobin levels >5% at screening. G6PD deficiency.

  • Positive HIV antibody, hepatitis B surface antigen or hepatitis C antibody at screening.
  • Pregnant or nursing women; women of childbearing potential who are unwilling or unable to use an appropriate form of contraception, from prior to study medication administration until 2 weeks following the last dose of investigational product.
  • Any contraindication to splenic aspirate (or bone marrow aspirate), including but not limited to PT prolonged >3 seconds longer than control or platelets <50,000 / mm3.
  • Subjects with a known hypersensitivity reaction to 8-aminoquinolines (e.g. primaquine) or any of the investigational product excipients.
  • Treatment with an established antileishmanial chemotherapeutic agent within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
  • Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
  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: NCT00381394

Locations
India
GSK Investigational Site
Muzaffarpur, India
GSK Investigational Site
Muzaffarpur, India, 842001
GSK Investigational Site
Patna, India, 800007
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00381394     History of Changes
Other Study ID Numbers: STQ105938
Study First Received: September 26, 2006
Last Updated: May 31, 2012
Health Authority: India: Ministry of Health

Keywords provided by GlaxoSmithKline:
amphotericin B
safety
tolerability and pharmacokinetics of oral sitamaquine
Visceral leishmaniasis

Additional relevant MeSH terms:
Leishmaniasis
Leishmaniasis, Visceral
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Skin Diseases, Parasitic
Skin Diseases, Infectious
Skin Diseases
Amphotericin B
Liposomal amphotericin B
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Bacterial Agents
Antifungal Agents

ClinicalTrials.gov processed this record on August 21, 2014