MalariaPhase 2NCT01713621
OZ439 PhIIa Study in Plasmodium Falciparum: Extended Observation
A Phase 2 study testing OZ439 in people with Malaria, run by Medicines for Malaria Venture at 3 sites in Thailand.
Trial summary
This study aims to investigate the concentration dependent effects of OZ439 on the clearance of P. falciparum parasites in patients, specifically the determination of an in-vivo minimum inhibitory concentration (MIC) of OZ439. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Malaria
- What is being tested?
- OZ439
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 3 sitesThailand
- Study dates
- Mar 2013to Apr 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male or female patients between the age of 18 and 60 years, inclusive
- Body weight between 45 kg and 90 kg inclusive
- Presence of mono-infection of P. falciparum confirmed by:
- Fever, as defined by axillary temperature ≥ 37.5°C or oral/rectal/tympanic temperature ≥ 38°C, or history of fever in the previous 24 hours (history of fever must be documented) and,
- Microscopically confirmed parasite infection: 1,000 to 75,000 asexual parasite count/µL blood.
- Written informed consent, in accordance with local practice, provided by patient. If the patient is unable to write, witnessed consent is permitted according to local ethical considerations
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- Ability to swallow oral medication
- Ability and willingness to participate and access the health facility
- Agree to hospitalization for at least 72h until parasites have fallen below the level of polymerase chain reaction (PCR) detection and have no signs or symptoms of malaria; and then to return once daily to the study centre for blood sampling for quantitative polymerase chain reaction (qPCR), and rehospitalisation when qPCR levels are detectable.
Who cannot join
- Patients with signs and symptoms of severe/complicated malaria requiring parenteral treatment according to the World Health Organization Criteria 2010
- Mixed Plasmodium infection
- Severe vomiting, defined as more than three times in the 24 hours prior to inclusion in the study or inability to tolerate oral treatment, or severe diarrhoea defined as 3 or more watery stools per day
- Presence of other serious or chronic clinical condition requiring hospitalization
- Severe malnutrition (defined as the weight-for-height being below -3 standard deviation or less than 70% of median of the NCHS/WHO normalized reference values)
- Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, QTc interval greater than or equal to 450 msec), respiratory (including active tuberculosis), history of jaundice, hepatic, renal, gastrointestinal, immunological (including active HIV-AIDS), neurological (including auditory), endocrine, infectious, malignancy, psychiatric, history of convulsions or other abnormality (including head trauma)
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- Known history of hypersensitivity, allergic or adverse reactions to artemisinin containing compounds or mefloquine
- Known active Hepatitis A Immunoglobulin M (IgM) (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab)
- Have received any antimalarial treatment in the preceding 14 days, as determined by history and screening test
- Have received antibacterial with known antimalarial activity in the preceding 14 days
- Have received an investigational drug within the past 4 weeks
- Liver function tests (Aspartate Aminotransferase(ASAT)/Alanine Aminotransferase (ALAT) levels) > 2x upper limit of normal (ULN) if Total Bilirubin normal or >1.5xULN if Total bilirubin between >1 and >1.5xULN
- Hemoglobin (Hb) level =< 8g/dl
- Total Bilirubin > 1.5XULN
- Serum creatinine levels more than 2 times the upper limit of normal range (>2xULN).
- Female patients must be neither pregnant as demonstrated by a negative serum pregnancy test at screening and urinary pregnancy test pre-dose (the result of the pre-dose assessment must be confirmed negative prior to dosing) nor lactating, and must be willing to take measures not to become pregnant during the study period and safety follow-up period.
Trial locations and contacts
3 sites in 1 country.
Thailand3 sites
Faculty of Tropical Medicine,
Bangkok, Bangkok, 10400
Mae Ramat District hospital
Mae Ramat, Changwat Tak, 63140
Shoklo Malaria Research Unit
Mae Sot, Changwat Tak, 63110
About this study
Official title: The Extended Observation Over a Period of 28 Days of the Effects of Single Doses of OZ439 on the Recrudescence of Plasmodium Falciparum Malaria - a PhIIa, Open Label Study in Adult Patients
This study aims to investigate the concentration dependent effects of OZ439 on the clearance of P. falciparum parasites in patients, specifically the determination of an in-vivo minimum inhibitory concentration (MIC) of OZ439. Characterisation of PK-PD (Pharmacokinetic-Pharmacodynamic) relationships is essential for rational evidence based dosing. The adaptive investigation of a range of doses will provide the best chance of accurate PK-PD characterisation, allowing the observation of Plasmodium falciparum growth dynamics and the subsequent identification of MIC and MPC (minimum parasiticidal concentration). Additionally the tolerability and pharmacokinetics of OZ439 will be confirmed. The PK/PD relationship between OZ439 exposure and subsequent effects on parasitaemia will be investigated.
- Conditions
- Malaria
- Being tested
- OZ439
- Keywords
- P. falciparum, malaria
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OZ439Drug
OZ439 is a novel synthetic trioxolane antimalarial agent
| Study group | Role | What they receive |
|---|---|---|
| OZ439 100mg | Experimental | Single dose of 100mg of OZ439 administered as an oral suspension Receives: Drug: OZ439 |
| OZ439 500mg | Experimental | Single dose of 500mg of OZ439 administered as an oral suspension Receives: Drug: OZ439 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Minimum Inhibitory Concentration (MIC) and Minimum Parasiticidal Concentration (MPC)
The estimated MIC and MPC were derived from the fitted parasitaemia concentration and PK/PD relationship.
Measured: up to 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2012 (estimated)
- Study startMar 2013
- Primary completionApr 2015
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medicines for Malaria Venture
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sasithon Pukrittayakamee, MD, Principal investigator, Faculty of Tropical Medicine, Mahidol University, BangkokFrancois Nosten, MD, Principal investigator, Shoklo Malaria Research Unit, Faculty of Tropical medicine, Mahidol University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01713621
- Sponsor's protocol ID
- MMV_OZ439_12_006
- Status last verified
- Mar 2017
- First submitted
- 22 Oct 2012
- Last updated
- 14 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Vennerstrom JL, Arbe-Barnes S, Brun R, Charman SA, Chiu FC, Chollet J, Dong Y, Dorn A, Hunziker D, Matile H, McIntosh K, Padmanilayam M, Santo Tomas J, Scheurer C, Scorneaux B, Tang Y, Urwyler H, Wittlin S, Charman WN. Identification of an antimalarial synthetic trioxolane drug development candidate. Nature. 2004 Aug 19;430(7002):900-4. doi: 10.1038/nature02779.
PubMed 15318224
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Extended Observation Over a Period of 28 Days of the Effects of Single Doses of OZ439 on the Recrudescence of Plasmodium Falciparum Malaria - a PhIIa, Open Label Study in Adult Patients
- ClinicalTrials.gov ID
- NCT01713621
- Acronym / sponsor ID
- MMV_OZ439_12_006
- Conditions
- Malaria
- Keywords
- P. falciparum, malaria
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Medicines for Malaria VentureUniversity, hospital or other
- Study start
- Mar 2013
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 25 Oct 2012 (estimated)
- Results
- Posted 10 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to investigate the concentration dependent effects of OZ439 on the clearance of P. falciparum parasites in patients, specifically the determination of an in-vivo minimum inhibitory concentration (MIC) of OZ439. Characterisation of PK-PD (Pharmacokinetic-Pharmacodynamic) relationships is essential for rational evidence based dosing. The adaptive investigation of a range of doses will provide the best chance of accurate PK-PD characterisation, allowing the observation of Plasmodium falciparum growth dynamics and the subsequent identification of MIC and MPC (minimum parasiticidal concentration). Additionally the tolerability and pharmacokinetics of OZ439 will be confirmed. The PK/PD relationship between OZ439 exposure and subsequent effects on parasitaemia will be investigated.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| OZ439 100mg | Experimental | Drug: OZ439Single dose of 100mg of OZ439 administered as an oral suspension |
| OZ439 500mg | Experimental | Drug: OZ439Single dose of 500mg of OZ439 administered as an oral suspension |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Male or female patients between the age of 18 and 60 years, inclusive
- Body weight between 45 kg and 90 kg inclusive
- Presence of mono-infection of P. falciparum confirmed by:
- Written informed consent, in accordance with local practice, provided by patient. If the patient is unable to write, witnessed consent is permitted according to local ethical considerations
- Ability to swallow oral medication
Key exclusion criteria (16 listed)
- Patients with signs and symptoms of severe/complicated malaria requiring parenteral treatment according to the World Health Organization Criteria 2010
- Mixed Plasmodium infection
- Severe vomiting, defined as more than three times in the 24 hours prior to inclusion in the study or inability to tolerate oral treatment, or severe diarrhoea defined as 3 or more watery stools per day
- Presence of other serious or chronic clinical condition requiring hospitalization
- Severe malnutrition (defined as the weight-for-height being below -3 standard deviation or less than 70% of median of the NCHS/WHO normalized reference values)
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 |
|---|---|---|
| OZ439OZ439 is a novel synthetic trioxolane antimalarial agent | Drug | OZ439 100mg, OZ439 500mg |
Primary outcome
Minimum Inhibitory Concentration (MIC) and Minimum Parasiticidal Concentration (MPC)
Time frame: up to 28 days
The estimated MIC and MPC were derived from the fitted parasitaemia concentration and PK/PD relationship.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15318224Vennerstrom JL, Arbe-Barnes S, Brun R, Charman SA, Chiu FC, Chollet J, Dong Y, Dorn A, Hunziker D, Matile H, McIntosh K, Padmanilayam M, Santo Tomas J, Scheurer C, Scorneaux B, Tang Y, Urwyler H, Wittlin S, Charman WN. Identification of an antimalarial synthetic trioxolane drug development candidate. Nature. 2004 Aug 19;430(7002):900-4. doi: 10.1038/nature02779.
- Individual participant dataSharing planned: No
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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.
Sasithon Pukrittayakamee, MD principal investigator
Faculty of Tropical Medicine, Mahidol University, Bangkok
Francois Nosten, MD principal investigator
Shoklo Malaria Research Unit, Faculty of Tropical medicine, Mahidol University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing OZ439 in people with Malaria, run by Medicines for Malaria Venture at 3 sites in Thailand.
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 9 inclusion and 16 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: finished, as of the sponsor's last update on 14 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Thailand. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Minimum Inhibitory Concentration (MIC) and Minimum Parasiticidal Concentration (MPC) (time frame: up to 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01713621, which also lists 1 linked publication.
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 14 Apr 2017.