Uncomplicated Falciparum MalariaPhase 2/3AMOSNCT00936767
Artemisone for the Treatment of Uncomplicated Falciparum Malaria in Western Cambodia
A Phase 2/3 study testing Artemisone/Mefloquine (AmiM3) and Artesunate in people with Uncomplicated Falciparum Malaria, run by University of Oxford at 1 site in Cambodia.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Uncomplicated Falciparum Malaria
- What is being tested?
- Artemisone/Mefloquine (AmiM3) and Artesunate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteCambodia
- Study dates
- Oct 2010to Oct 2010
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Artemisone for the Treatment of Uncomplicated Falciparum Malaria in Western
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).
Read the detailed description
This is a small detailed randomised open-label clinical trial comparing the efficacy of oral artemisone with oral artesunate in the treatment of uncomplicated falciparum malaria in Western Cambodia. A detailed pharmacokinetic-pharmacodynamic evaluation and in vitro sensitivity for the study drugs will be part of the assessments. The overall design and proposed conduct is very similar to the recently completed studies of high dose artesunate.Fever patients in the villages surrounding Pailin (or equivalent study site) in Western Cambodia will be screened with a PfHRP2-based malaria rapid test (Paracheck) by the village malaria workers. In case of a positive test result, the patient will be transported by the study team to the hospital, full consent (as described above) and enrolment procedures will be conducted. It will be made clear from the outset that refusal to participate will in no way jeopardize subsequent antimalarial treatment.Eligibility can only be confirmed by a medically qualified investigator. Subjects who fulfil all the inclusion criteria and have none of the exclusion criteria will be randomised to one of the three treatment arms according to the randomisation schedule. Subject numbers will be will be assigned when the subject is enrolled after screening and prior to randomisation.Patients will be randomized in blocks of 15 to receive either artemisone 4 mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4 (N=50) or artesunate 4mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4 (N=25.
- Conditions
- Uncomplicated Falciparum Malaria
- Being tested
- Artemisone/Mefloquine (AmiM3), Artesunate
- Keywords
- falciparum malaria, artemisone, artesunate, resistance
- Medical subject headings
- Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
ArtesunateDrug
Artesunate 4mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Artesunate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Presence of light microscopic assessed peripheral blood parasitaemia at 72 hours after start of antimalarial treatment.
Measured: 72 hours
Secondary outcomes (9)
Parasite clearance times (PCT, slope of the log clearance curve, PRR24, PRR48, PC50, PC90)
Measured: Variable
Cure rate defined as clearance of asexual parasites without recrudescence within a 28 and 63-day period.
Measured: 63 days
Number of adverse events
Measured: 9 weeks
Fever clearance time
Measured: Variable
In-vitro sensitivity to antimalarial drugs of P. falciparum from study patients
Measured: Day 0
Molecular determinants of antimalarial drug resistance.
Measured: Day 0
Pharmacokinetic parameters
Measured: Day 2
Hematocrit levels
Measured: Day 63
Gametocyte clearance
Measured: Variable
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2009 (estimated)
- Study startOct 2010
- Primary completionOct 2010 (estimated)
- Study completionOct 2010 (estimated)
Why it stopped: Did not get approval
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Uncomplicated Falciparum MalariaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Mahidol University, Medicines for Malaria Venture
- Responsible party
- Sponsor
- Investigators
- Duong Socheat, MD, Principal investigator, Cambodia National Malaria Control Programme
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00936767
- Sponsor's protocol ID
- BAKMAL0901
- Acronym
- AMOS
- Status last verified
- Oct 2010
- First submitted
- 9 Jul 2009
- Last updated
- 31 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Artemisone for the Treatment of Uncomplicated Falciparum Malaria in Western
- ClinicalTrials.gov ID
- NCT00936767
- Acronym / sponsor ID
- AMOS / BAKMAL0901
- Conditions
- Uncomplicated Falciparum Malaria
- Keywords
- falciparum malaria, artemisone, artesunate, resistance
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Did not get approval
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Mahidol University, Medicines for Malaria Venture
- Study start
- Oct 2010
- Primary completion
- Oct 2010 (estimated)
- Study completion
- Oct 2010 (estimated)
- First posted
- 10 Jul 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
This is a small detailed randomised open-label clinical trial comparing the efficacy of oral artemisone with oral artesunate in the treatment of uncomplicated falciparum malaria in Western Cambodia. A detailed pharmacokinetic-pharmacodynamic evaluation and in vitro sensitivity for the study drugs will be part of the assessments. The overall design and proposed conduct is very similar to the recently completed studies of high dose artesunate.Fever patients in the villages surrounding Pailin (or equivalent study site) in Western Cambodia will be screened with a PfHRP2-based malaria rapid test (Paracheck) by the village malaria workers. In case of a positive test result, the patient will be transported by the study team to the hospital, full consent (as described above) and enrolment procedures will be conducted. It will be made clear from the outset that refusal to participate will in no way jeopardize subsequent antimalarial treatment.Eligibility can only be confirmed by a medically qualified investigator. Subjects who fulfil all the inclusion criteria and have none of the exclusion criteria will be randomised to one of the three treatment arms according to the randomisation schedule. Subject numbers will be will be assigned when the subject is enrolled after screening and prior to randomisation.Patients will be randomized in blocks of 15 to receive either artemisone 4 mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4 (N=50) or artesunate 4mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4 (N=25.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Artemisone/Mefloquine (AmiM3) | Experimental | Drug: Artemisone/Mefloquine (AmiM3)Artemisone 4 mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4 |
| Artesunate/Mefloquine (MAS3) | Active comparator | Drug: ArtesunateArtesunate 4mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4 |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Artemisone/Mefloquine (AmiM3)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) |
| ArtesunateArtesunate 4mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4 | Drug | Artesunate/Mefloquine (MAS3) |
Primary outcome
Presence of light microscopic assessed peripheral blood parasitaemia at 72 hours after start of antimalarial treatment.
Time frame: 72 hours
9 secondary outcomes
Parasite clearance times (PCT, slope of the log clearance curve, PRR24, PRR48, PC50, PC90)
Time frame: Variable
Cure rate defined as clearance of asexual parasites without recrudescence within a 28 and 63-day period.
Time frame: 63 days
Number of adverse events
Time frame: 9 weeks
Fever clearance time
Time frame: Variable
In-vitro sensitivity to antimalarial drugs of P. falciparum from study patients
Time frame: Day 0
Molecular determinants of antimalarial drug resistance.
Time frame: Day 0
Pharmacokinetic parameters
Time frame: Day 2
Hematocrit levels
Time frame: Day 63
Gametocyte clearance
Time frame: Variable
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Duong Socheat, MD principal investigator
Cambodia National Malaria Control Programme
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Artemisone/Mefloquine (AmiM3) and Artesunate in people with Uncomplicated Falciparum Malaria, run by University of Oxford at 1 site in Cambodia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 31 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Cambodia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Presence of light microscopic assessed peripheral blood parasitaemia at 72 hours after start of antimalarial treatment. (time frame: 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2018.