Arterolane-PQP Versus DHA-PQP in Uncomplicated Falciparum Malaria in Eastern Myanmar

NCT ID: NCT02461186

Last Updated: 2015-11-03

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2/PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2017-06-30

Brief Summary

Emerging resistance to artemisinins and their partner drugs severely threatens the treatment of falciparum malaria in Myanmar with artemisinin combination therapies. To inform drug policy, it is crucial to evaluate alternative antimalarial treatments.

The investigators here propose a randomized clinical trial comparing parasite clearance parameters and efficacy of 3 days arterolane-piperaquine with standard treatment with 3 days dihydroartemisinin (DHA)-piperaquine in adult patients with uncomplicated falciparum malaria in Myanmar stratified for the presence of "K13" mutation in the infecting parasite strains.

Detailed Description

Primary Objective:

• To assess the parasite clearance half-life of arterolane-piperaquine compared to DHA-piperaquine in patients with artemisinin resistant uncomplicated falciparum malaria, defined by presence of the "K13" mutations in the infecting parasite strain.

Secondary Objectives :

• To assess the therapeutic efficacy of arterolane-piperaquine and DHA-piperaquine for the treatment of uncomplicated falciparum malaria or mixed infection (P.falciparum (PF) + a non-falciparum species) at Day 42, stratified by presence of artemisinin resistance in the infecting parasite strain.
• To assess the frequency of adverse events and serious adverse events of arterolane-piperaquine compared to DHA-piperaquine.
• To assess other efficacy parameters related to parasite clearance and parasite cure rate as well as the gametocyte carriage.
• To obtain pharmacokinetic (PK) and pharmacokinetic/pharmacodynamics (PK/PD) data on arterolane-piperaquine and DHA-piperaquine.

Conditions

Uncomplicated Falciparum Malaria; Artemisinin-resistant

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arterolane maleate-piperaquine phosphate (Synriam)

Group Type: EXPERIMENTAL

Arterolane maleate-piperaquine phosphate (Synriam)

Intervention Type: DRUG

Dihydroartemisinin-piperaquine phosphate (Duocotexin)

Group Type: EXPERIMENTAL

Dihydroartemisinin-piperaquine phosphate (Duocotexin)

Intervention Type: DRUG

Interventions

Arterolane maleate-piperaquine phosphate (Synriam)

Intervention Type: DRUG

Dihydroartemisinin-piperaquine phosphate (Duocotexin)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female aged ≥ 18 year old
• Symptomatic malaria infection, i.e. history of fever or presence of fever >37.5°c (tympanic) within the last 24 hours.
• Microscopic confirmation of asexual stages of P.falciparum (may be mixed with non-falciparum species) with a parasitaemia >10,000 parasites/µL
• Able to take oral medication
• Willingness and ability of patients to comply with the study protocol for the duration of the study
• Written informed consent given to participate in the trial

Exclusion Criteria

• Pregnancy or lactation (urine test for β HCG to be performed on any woman of child bearing age 18 to 45 year old)
• P.falciparum asexual stage parasitaemia greater than or equal to 4% red blood cells (175,000/µL).
• Signs or symptoms indicative of severe malaria:

• Impaired consciousness
• Severe anaemia (Hct<15%)
• Bleeding disorder -evidenced by epistaxis, bleeding gums, frank haematuria, bleeding from venipuncture sites
• Respiratory distress
• Severe jaundice
• Have taken a full course DHA-piperaquine, artemether-lumefantrin or other antimalarial treatment in the previous 42 days
• Known hypersensitivity to artemisinins or to piperaquine - defined as history of erythroderma/other severe cutaneous reaction or angioedema
• History of splenectomy
• History of taking medicinal products that are known to prolong the QTc interval, including:

• Antiarrhythmics (e.g. amiodarone, disopyramide, dofetilide, ibutilide, procainamide, quinidine, hydroquinidine, sotalol).
• Neuroleptics (e.g. phenothiazines, sertindole, sultopride, chlorpromazine, haloperidol, mesoridazine, pimozide, or thioridazine), antidepressive agents.
• Certain antimicrobial agents, including agents of the following classes:

• macrolides (e.g. erythromycin, clarithromycin),
• fluoroquinolones (e.g. moxifloxacin, sparfloxacin),
• imidazole and triazole antifungal agent,
• pentamidine and saquinavir.
• The non-sedating antihistamines terfenadine, astemizole, mizolastine.
• Other drugs: cisapride, droperidol, domperidone, bepridil, diphemanil, probucol, levomethadyl, methadone, vinca alkaloids, arsenic trioxide.
• History of taking any drug which is known to be metabolised by the cytochrome enzyme CYP2D6 including flecainide, metoprol, imipramine, amitriptyline, clomipramine.
• Family history of sudden unexplained death, or personal or family history of predisposing cardiac conditions for arrhythmia/QT prolongation (including congenital long QT syndrome, arrhythmia, QTc interval greater than 450 milliseconds with either Bazett or Fridericia correction).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mahidol Oxford Tropical Medicine Research Unit

OTHER

Sponsor Role: collaborator

Department of Medical Research, Lower Myanmar

OTHER

Sponsor Role: collaborator

University of Oxford

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Arjen M Dondorp, MD

Role: PRINCIPAL_INVESTIGATOR

Mahidol Oxfrod Tropical Medicine Research Unit

Other Identifiers

BAKMAL1501

Identifier Type: -

Identifier Source: org_study_id