Plasmodium Falciparum MalariaPhase 2NCT00362050
RBx11160 Phase II Dose Ranging Study RBx/MMV05-06
A Phase 2 study testing Treatment with 3 dose groups of RBx11160 over 7 days in people with Plasmodium Falciparum Malaria, run by Medicines for Malaria Venture at 4 sites in 3 countries.
Trial summary
The trial will identify the best dose of the synthetic peroxide RBx11160 to treat uncomplicated malaria. Patients will be treated over 7 days with daily doses of 50, 100 or 200 mg RBx11160. Read more about this study
- Who is it for?
- Ages 13 to 65 years
- Conditions the study is for
- Plasmodium Falciparum Malaria
- What is being tested?
- Treatment with 3 dose groups of RBx11160 over 7 days
- How many people
- 255 participants
- Where
- 4 sitesin 3 countries
- Study dates
- Jun 2006to Jan 2007
- Phase
- Phase 2
- 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 13 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female patients aged 13 to 65 years, inclusive.
- Body weight > 30 kg with no clinical evidence of severe malnutrition.
- Presence of acute symptomatic uncomplicated malaria with a diagnosis confirmed by a positive blood smear with asexual forms of P. falciparum parasites only. Initial parasite densities appropriate for inclusion will be between 1000 and 100,000 asexual parasites/microL blood.
- Presence of fever (axillary temperature > 37.5 °C or oral or rectal temperature > 38 °C).
- Female patients must be non-lactating and willing to use contraceptive methods during the study period.
- Written informed consent, in accordance with local practice, provided by patient and/or parent/guardian/spouse. If a patient is unable to provide informed consent in writing, a thumbprint to indicate consent in the presence of at least 1 witness is acceptable. If applicable, for adolescents providing written informed consent, assent should be obtained from the patient's legally accepted representative/guardian.
- Willingness and ability to comply with the study protocol for the duration of the study.
- Patient resides within a reasonable distance of the investigational site, so that attendance of all study visits and follow-up by medical staff are logistically feasible.
Who cannot join
- Patients presenting with a mixed infection (i.e., malaria due to more than 1 causative parasite).
- Patients with severe malaria.
- Any antimalarial treatment during 2 weeks prior to Screening, as assessed by medical history.
- History of hypersensitivity or allergic reactions to artemisinins.
- Patients who have been treated with RBx 11160 in any study.
- Participation in any investigational drug study during the 30 days prior to Screening.
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- Electrocardiogram (ECG) abnormalities with clinical significance or relevance that require urgent management. These abnormalities include QTc interval > 450 msec at Screening and cardiac conduction disorders, with the exception of right bundle branch block.
- A female patient who is lactating or pregnant at Screening.
- Gastrointestinal dysfunction that could alter absorption or motility (e.g., diarrhea defined as > 3 episodes of watery stools in the previous 24 hours or patients who have had 3 episodes of vomiting within 24 hours prior to Screening).
- Patients with known significant renal or hepatic impairment indicated by the following laboratory evaluations at Screening:
- Serum creatinine > 1.5 x upper limit of normal (ULN). Aspartate transaminase > 2.5 x ULN. Alanine transaminase > 2.5 x ULN. Alkaline phosphatase > 2.5 x ULN. Total bilirubin > 1.5 x ULN.
- Patients who have had a splenectomy.
- Immunocompromised patients, patients receiving immunosuppressive agents, or patients with known human immunodeficiency virus (HIV) infection. (Screening for these conditions is not required for entry in the study.)
- Evidence of clinically significant cardiovascular, pulmonary, metabolic, gastrointestinal, neurological, psychiatric (e.g., depression, anxiety, psychosis, or schizophrenia) or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied).
- Patients who have epilepsy or a history of convulsions.
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
Tanzania2 sites
District Hospital Bagamayo
Dar es Salaam
Public Health Care Center
Kivunge, Zanzibar
India1 site
Field Station Malaria Reseach Centre (Indian Council of Medical Research)
Rourkela, Odisha, 769 002
Thailand1 site
Faculty of Tropical Medicine, 420/6 Rajavithee Road
Bangkok, 10400
About this study
Official title: A Phase II, Double-Blind, Parallel-Group, Randomized, Dose-Ranging Study Assessing the Antimalarial Activity and Safety of RBx 11160 Administered for 7 Days in Patients With Acute Uncomplicated Plasmodium Falciparum Malaria
The trial will identify the best dose of the synthetic peroxide RBx11160 to treat uncomplicated malaria. Patients will be treated over 7 days with daily doses of 50, 100 or 200 mg RBx11160.
The study is designed to assess the antimalarial activity and safety of 3 dose levels of RBx 11160 administered once daily for 7 consecutive days. The primary endpoint will be the time to 90% parasite clearance. In future regulatory studies, RBx 11160 is likely to be administered in combination with another antimalarial agent since the development plan follows the current recommendation of WHO for the treatment of uncomplicated malaria. However, it is critical to gather data on RBx 11160 when used as monotherapy in adult patients suffering from acute uncomplicated P. falciparum malaria. In malaria-endemic regions, an adult population is defined on the basis of immune status rather than the legal age of consent. Thus, patients as young as 13 years of age can be enrolled provided consent has been obtained from a legal guardian in accordance with local practices and regulations. This study will be conducted in compliance with International Conference on Harmonization (ICH) Good Clinical Practice (GCP).
Read the detailed description
This is a Phase II, double-blind, multicenter, randomized, parallel-group, dose-ranging study of the antimalarial activity and safety of 3 (50, 100, and 200 mg) RBx 11160 dose levels administered as a single dose orally for 7 consecutive days in patients with acute uncomplicated P. falciparum malaria (mono-infection).
At least 255 patients will be randomized at 4 study sites in South East Asia, India and Africa. Each investigational site will enroll between 60 and 90 patients to yield approximately 65 "per protocol" patients in each treatment arm . Patients will be randomized to 1 of 3 dose groups. Patients will be administered RBx 11160 with matching placebo tablets as required to maintain the study blind.
The study is divided into 3 main periods including the Pre-Treatment Period (Screening/Day 0), the Treatment Period (Days 0 through 6; Day 0 is the first day of study medication dosing), and the Post-Treatment Period (Day 14 +/- 1 day; Day 21 +/- 1 day; and Day 28 +/- 2 days).
Patient participation will be for at least 28 (± 2) days following the first dose of study medication. Patients will be hospitalized for at least 4 days (Days 0, 1, 2, and 3), but may remain in the hospital or live in the vicinity of the study site for the study duration. If a patient is discharged from the hospital on Day 3, he/she will return to the study site or an authorized study staff member will visit the patient on Days 4 and 5 to administer study medication and perform indicated assessments. The patient will return to the study site for study visits on Days 6 (last dose of study medication administration), 14, 21, and 28.
If adverse events reported during the study are unresolved by Day 28, patients will be followed for an additional 30 days or until resolution of the event or determination that no further medical management is deemed necessary. Similarly, the investigator will instruct the patient to return to the study site if any untoward event occurs within 30 days of completing study medication.
- Conditions
- Plasmodium Falciparum Malaria
- Being tested
- Treatment with 3 dose groups of RBx11160 over 7 days
- Keywords
- malaria, falciparum, uncomplicated Plasmodium falciparum malaria
- Medical subject headings
- Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treatment with 3 dose groups of RBx11160 over 7 daysDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Median time to 90% parasite clearance (PC90).
Secondary outcomes (9)
Median time to 50% parasite clearance
Median parasite clearance time
Fever clearance time
Proportion of patients with Polymerase Chain Reaction (PCR)-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 28. Proportion of patients with PCR-uncorrected ACPR on Day 28.
Proportion of patients with PCR-uncorrected ACPR on Day 14.
Relationship between RBx 11160 plasma concentrations at approximately 3 hours and 8 hours after study medication administration on Days 0 and 6 and PC90, PC50 and PCT.
Number of gametocytes at Days 0, 3, 6, 14, 21, and 28.
Safety endpoints:
Incidence of adverse events or clinically significant changes in laboratory parameters, physical examination, ECG, or vital signs.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2006 (estimated)
- Study startJun 2006
- Study completionJan 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Plasmodium Falciparum 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 255 participants
Sponsor and investigators
- Lead sponsor
- Medicines for Malaria Venture
- Sponsor type
- University, hospital or other
- Collaborators
- Ranbaxy Laboratories Limited, Swiss Tropical & Public Health Institute
- Investigators
- Sornchai Looareesuwan, MD, Principal investigator, Mahidol UniversitySalim M Abdulla, MD, Principal investigator, District Hospital Bagamoyo, Dar es Salaam, TanzaniaAnders Björkman, MD, Principal investigator, Kivunge Public Health Care Center, Zanzibar, TanzaniaNeena Valecha, MD, Principal investigator, Malaria Research Center, Rourkela, India
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00362050
- Sponsor's protocol ID
- RBx/MMV05-06
- Status last verified
- Aug 2007
- First submitted
- 8 Aug 2006
- Last updated
- 29 Aug 2007
- Results posted
- 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 15318224Tang Y, Dong Y, Vennerstrom JL. Synthetic peroxides as antimalarials. Med Res Rev. 2004 Jul;24(4):425-48. doi: 10.1002/med.10066.
PubMed 15170591Valecha N, Looareesuwan S, Martensson A, Abdulla SM, Krudsood S, Tangpukdee N, Mohanty S, Mishra SK, Tyagi PK, Sharma SK, Moehrle J, Gautam A, Roy A, Paliwal JK, Kothari M, Saha N, Dash AP, Bjorkman A. Arterolane, a new synthetic trioxolane for treatment of uncomplicated Plasmodium falciparum malaria: a phase II, multicenter, randomized, dose-finding clinical trial. Clin Infect Dis. 2010 Sep 15;51(6):684-91. doi: 10.1086/655831.
PubMed 20687837
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Double-Blind, Parallel-Group, Randomized, Dose-Ranging Study Assessing the Antimalarial Activity and Safety of RBx 11160 Administered for 7 Days in Patients With Acute Uncomplicated Plasmodium Falciparum Malaria
- ClinicalTrials.gov ID
- NCT00362050
- Acronym / sponsor ID
- RBx/MMV05-06
- Conditions
- Plasmodium Falciparum Malaria
- Keywords
- malaria, falciparum, uncomplicated Plasmodium falciparum malaria
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 255 participants
- Lead sponsor
- Medicines for Malaria VentureUniversity, hospital or other
- Collaborators
- Ranbaxy Laboratories Limited, Swiss Tropical & Public Health Institute
- Study start
- Jun 2006
- Study completion
- Jan 2007 (actual)
- First posted
- 9 Aug 2006 (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.
The trial will identify the best dose of the synthetic peroxide RBx11160 to treat uncomplicated malaria. Patients will be treated over 7 days with daily doses of 50, 100 or 200 mg RBx11160.
The study is designed to assess the antimalarial activity and safety of 3 dose levels of RBx 11160 administered once daily for 7 consecutive days. The primary endpoint will be the time to 90% parasite clearance. In future regulatory studies, RBx 11160 is likely to be administered in combination with another antimalarial agent since the development plan follows the current recommendation of WHO for the treatment of uncomplicated malaria. However, it is critical to gather data on RBx 11160 when used as monotherapy in adult patients suffering from acute uncomplicated P. falciparum malaria. In malaria-endemic regions, an adult population is defined on the basis of immune status rather than the legal age of consent. Thus, patients as young as 13 years of age can be enrolled provided consent has been obtained from a legal guardian in accordance with local practices and regulations. This study will be conducted in compliance with International Conference on Harmonization (ICH) Good Clinical Practice (GCP).
Detailed description
This is a Phase II, double-blind, multicenter, randomized, parallel-group, dose-ranging study of the antimalarial activity and safety of 3 (50, 100, and 200 mg) RBx 11160 dose levels administered as a single dose orally for 7 consecutive days in patients with acute uncomplicated P. falciparum malaria (mono-infection).
At least 255 patients will be randomized at 4 study sites in South East Asia, India and Africa. Each investigational site will enroll between 60 and 90 patients to yield approximately 65 "per protocol" patients in each treatment arm . Patients will be randomized to 1 of 3 dose groups. Patients will be administered RBx 11160 with matching placebo tablets as required to maintain the study blind.
The study is divided into 3 main periods including the Pre-Treatment Period (Screening/Day 0), the Treatment Period (Days 0 through 6; Day 0 is the first day of study medication dosing), and the Post-Treatment Period (Day 14 +/- 1 day; Day 21 +/- 1 day; and Day 28 +/- 2 days).
Patient participation will be for at least 28 (± 2) days following the first dose of study medication. Patients will be hospitalized for at least 4 days (Days 0, 1, 2, and 3), but may remain in the hospital or live in the vicinity of the study site for the study duration. If a patient is discharged from the hospital on Day 3, he/she will return to the study site or an authorized study staff member will visit the patient on Days 4 and 5 to administer study medication and perform indicated assessments. The patient will return to the study site for study visits on Days 6 (last dose of study medication administration), 14, 21, and 28.
If adverse events reported during the study are unresolved by Day 28, patients will be followed for an additional 30 days or until resolution of the event or determination that no further medical management is deemed necessary. Similarly, the investigator will instruct the patient to return to the study site if any untoward event occurs within 30 days of completing study medication.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 13 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female patients aged 13 to 65 years, inclusive.
- Body weight > 30 kg with no clinical evidence of severe malnutrition.
- Presence of acute symptomatic uncomplicated malaria with a diagnosis confirmed by a positive blood smear with asexual forms of P. falciparum parasites only. Initial parasite densities appropriate for inclusion will be between 1000 and 100,000 asexual parasites/microL blood.
- Presence of fever (axillary temperature > 37.5 °C or oral or rectal temperature > 38 °C).
- Female patients must be non-lactating and willing to use contraceptive methods during the study period.
Key exclusion criteria (15 listed)
- Patients presenting with a mixed infection (i.e., malaria due to more than 1 causative parasite).
- Patients with severe malaria.
- Any antimalarial treatment during 2 weeks prior to Screening, as assessed by medical history.
- History of hypersensitivity or allergic reactions to artemisinins.
- Patients who have been treated with RBx 11160 in any 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 |
|---|---|---|
| Treatment with 3 dose groups of RBx11160 over 7 days | Drug | – |
Primary outcome
Median time to 90% parasite clearance (PC90).
9 secondary outcomes
Median time to 50% parasite clearance
Median parasite clearance time
Fever clearance time
Proportion of patients with Polymerase Chain Reaction (PCR)-corrected Adequate Clinical and Parasitological Response (ACPR) on Day 28. Proportion of patients with PCR-uncorrected ACPR on Day 28.
Proportion of patients with PCR-uncorrected ACPR on Day 14.
Relationship between RBx 11160 plasma concentrations at approximately 3 hours and 8 hours after study medication administration on Days 0 and 6 and PC90, PC50 and PCT.
Number of gametocytes at Days 0, 3, 6, 14, 21, and 28.
Safety endpoints:
Incidence of adverse events or clinically significant changes in laboratory parameters, physical examination, ECG, or vital signs.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2007.
- 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.
- Background: PubMed 15170591Tang Y, Dong Y, Vennerstrom JL. Synthetic peroxides as antimalarials. Med Res Rev. 2004 Jul;24(4):425-48. doi: 10.1002/med.10066.
- Derived from this study: PubMed 20687837Valecha N, Looareesuwan S, Martensson A, Abdulla SM, Krudsood S, Tangpukdee N, Mohanty S, Mishra SK, Tyagi PK, Sharma SK, Moehrle J, Gautam A, Roy A, Paliwal JK, Kothari M, Saha N, Dash AP, Bjorkman A. Arterolane, a new synthetic trioxolane for treatment of uncomplicated Plasmodium falciparum malaria: a phase II, multicenter, randomized, dose-finding clinical trial. Clin Infect Dis. 2010 Sep 15;51(6):684-91. doi: 10.1086/655831.
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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.
Sornchai Looareesuwan, MD principal investigator
Mahidol University
Salim M Abdulla, MD principal investigator
District Hospital Bagamoyo, Dar es Salaam, Tanzania
Anders Björkman, MD principal investigator
Kivunge Public Health Care Center, Zanzibar, Tanzania
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Treatment with 3 dose groups of RBx11160 over 7 days in people with Plasmodium Falciparum Malaria, run by Medicines for Malaria Venture at 4 sites in 3 countries.
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 8 inclusion and 15 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 29 Aug 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Tanzania, India, 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Median time to 90% parasite clearance (PC90).. 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 NCT00362050, which also lists 3 linked publications.
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 29 Aug 2007.