Artemisone for the Treatment of Uncomplicated Falciparum Malaria in Western Cambodia

NCT00936767 | Withdrawn Phase 2 DMC

• 1 other identifier: BAKMAL0901
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

It has now been demonstrated clearly that in Western Cambodia parasitological responses to artesunate and artemether containing treatment regimens for uncomplicated falciparum malaria are slower than elsewhere in the world. Median parasite clearance time (PCT) in patients treated with artesunate 4 mg/kg/day was 78 hours and with 2 mg/kg/day 82 hours, compared to 54 and 48 hours, respectively, in Western Thailand; at 72hours peripheral blood parasitaemia was still detectable in 55% of patients in Western Cambodia, compared to 7.5% in Western Thailand. Although occasional poor responses to artesunate have been described previously the current reports suggest a consistent problem. These antimalarials are central to current treatment strategies, and so spread of parasites with reduced artemisinin susceptibility outside this area would be a disaster. A recent consensus meeting Pnomh Penh agreed that this should indeed be termed resistance, and represented a major threat to malaria control. Radical containment measures would be needed. This study aims to address whether a semi-synthetic or fully synthetic peroxide antimalarial would be more effective than artesunate and could therefore be used in Cambodia as part of the elimination strategy. Artemisone is a semisynthetic derivative of dihydroartemisinin, which importantly changes its tertiary structure. This drug has also shown promising efficacy for the treatment of uncomplicated falciparum malaria in phase II trials in Thailand and seems to be at least as efficacious as artesunate. No significant toxicity has been reported for artemisone and it is very well tolerated. If sensitivity for artemisone has remained intact in Western Cambodia, this will have important implications for the strategies available for containment of the threatening problem of artesunate resistance in Western Cambodia. It will also have important implications for further development of these drugs for the use in artemisinin combination therapies (ACTs).

Conditions

Uncomplicated Falciparum Malaria

Keywords

falciparum malaria; artemisone; artesunate; resistance

Outcome Measures

Primary Outcomes (1)

• Presence of light microscopic assessed peripheral blood parasitaemia at 72 hours after start of antimalarial treatment.

  72 hours

Secondary Outcomes (9)

• Parasite clearance times (PCT, slope of the log clearance curve, PRR24, PRR48, PC50, PC90)

  Variable

• Cure rate defined as clearance of asexual parasites without recrudescence within a 28 and 63-day period.

  63 days

• Number of adverse events

  9 weeks

• Fever clearance time

  Variable

• In-vitro sensitivity to antimalarial drugs of P. falciparum from study patients

  Day 0

Study Arms (2)

Artemisone/Mefloquine (AmiM3)

EXPERIMENTAL

Artemisone 4 mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4

Drug: Artemisone/Mefloquine (AmiM3)

Artesunate/Mefloquine (MAS3)

ACTIVE COMPARATOR

Artesunate 4mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4

Drug: Artesunate

Interventions

Artemisone/Mefloquine (AmiM3) DRUG

Artemisone 4 mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4

Artemisone/Mefloquine (AmiM3)

Artesunate DRUG

Artesunate 4mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4

Artesunate/Mefloquine (MAS3)

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 16 years
• Full written informed consent is obtained
• Willingness and ability to comply with the study protocol for the duration of the trial including agreement to 5 days hospitalisation.
• History of fever or presence of fever (tympanic or axillary temperature at \>37.5 °C).
• Peripheral blood P.falciparum parasitaemia between 10,000/uL and 200,000/uL. (Mixed malaria infection included)

You may not qualify if:

• Known hypersensitivity to the study drugs.
• Any antimalarial drug treatment in the 48 hours prior to enrolment.
• Clinical and/or laboratory features of severe malaria (as defined by WHO).
• Gastrointestinal dysfunction that could alter absorption or motility (i.e. active peptic ulcer, inflammatory bowel disease, malabsorption syndromes, intestinal sub-occlusion or previous major gastrointestinal surgery).
• Presence of intercurrent illness or any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study.
• Splenectomy.
• Pregnant or lactating women. Serum test for β-HCG to be performed on any woman of child bearing age unless menstruating.
• Taking any contraindicated medicines (as listed in the most up to date product information)
• Participation in a clinical study within the previous 12 weeks
• Any other condition in the opinion of the investigator makes the patient unsuitable to be a subject

Sponsors & Collaborators

• University of Oxford: lead
• Mahidol University: collaborator
• Medicines for Malaria Venture: collaborator

Study Sites (1)

Pailin Hospital

Pailin, Cambodia

Location

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

artemisone; Mefloquine; Artesunate

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons

Study Officials

• Duong Socheat, MD

  Cambodia National Malaria Control Programme

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2009
• First Posted: July 10, 2009
• Study Start: October 1, 2010
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: August 31, 2018

Record last verified: 2010-10

Locations

CA (1)