MalariaPhase 2JP011NCT01464125
Fosmidomycin and Azithromycin for Acute Uncomplicated Plasmodium Falciparum Malaria (P. Malaria) in Adults
A Phase 2 study testing Fosmidomycin and Azithromycin in people with Malaria, run by Jomaa Pharma GmbH at 1 site in Thailand.
Trial summary
The aim of this study is to evaluate the role of azithromycin as a possible combination partner for fosmidomycin to protect it from its susceptibility to recrudescent infections when used as monotherapy for acute Plasmodium falciparum malaria while retaining its excellent safety profile. Read more about this study
- Who is it for?
- Ages 15 to 55 years
- Conditions the study is for
- Malaria
- What is being tested?
- Fosmidomycin and Azithromycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteThailand
- Study dates
- Nov 2008to Dec 2011
- 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 15 to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- male and female subjects aged 15 to 55 years
- body mass index ≥ 18.5kg/M2
- uncomplicated P falciparum malaria with acute manifestations
- asexual parasitaemia between 500uL and 100,000uL
- ability to tolerate oral therapy
- able to give informed signed consent
Who cannot join
- signs of severe malaria, according to WHO criteria
- body mass index ≤ 18.5 kg/M2
- pregnancy by history or by positive urine test
- lactation
- mixed plasmodial infection
- concomitant disease masking assessment of response, including diabetes, uncontrolled hypertension, heart failure, hepatic dysfunction (alanine-amino transferase > 150 U/L), renal impairment (creatinine > 125 umol/L or 3 mg/dl), haemoglobin < 8g/dl, white cell count > 12000/uL
- anti-malarial treatment within previous 28 days
- symptomatic AIDS
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of Fosmidomycin and Azithromycin When Administered Concurrently to Adult Subjects With Acute Uncomplicated Plasmodium Falciparum Malaria
The aim of this study is to evaluate the role of azithromycin as a possible combination partner for fosmidomycin to protect it from its susceptibility to recrudescent infections when used as monotherapy for acute Plasmodium falciparum malaria while retaining its excellent safety profile.
Read the detailed description
The scientific rationale for the use of this combination is to inhibit the ability of the parasite to synthesise isoprenoids, as precursors of many essential compounds including sterols, carotenoids and ubiquinones. This is effected through blockade of the non-mevalonate pathway by fosmidomycin as a potent inhibitor of 1-deoxy-D-xylulose 5-phosphate reductoisomerase coupled with targeting of protein biosynthesis by azithromycin through binding to the 50S ribosomal subunit. This mode of action contrasts with the ability of the human host to utilise the mevalonate pathway for isoprenoid synthesis and accounts for the safety profiles of both drugs through the mechanism of selective toxicity. Moreover it affords protection against cross resistance with existing chemotherapeutic agents.
The dose of fosmidomycin, equivalent to 30mg/kg twice daily for three days, selected for evaluation in this proof of concept study is derived from the highest dose that was administered in the Phase I safety tolerance studies. While the recommended dose of azithromycin for the treatment of bacterial infections is 250mg daily for three days, higher doses of up to 1500mg daily for three days have been evaluated for the treatment of malaria, in combination with artesunate or quinine.
- Conditions
- Malaria
- Being tested
- Fosmidomycin, Azithromycin
- Keywords
- Malaria, Plasmodium falciparum, acute uncomplicated
- Medical subject headings
- Malaria, Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FosmidomycinDrug
Fosmidomycin sodium capsules 450 mg x 4 twelve-hourly for three days
AzithromycinDrug
Azithromycin capsules 250 mg x 3 twelve-hourly for three days
| Study group | Role | What they receive |
|---|---|---|
| Fos-Azi | Experimental | Open label single arm concurrent administration of fosmidomycin and azithromycin. Receives: Drug: Fosmidomycin; Drug: Azithromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
day 28 cure rate of >95%
Efficacy of fosmidomycin and azithromycin when co-administered to adults with acute uncomplicated P.falciparum malaria.
Day 7 cure rate and Day 28 cure rates will be calculated from the following ratio: Number of subjects with clearance of asexual parasitaemia within seven days of commencement of treatment, without subsequent recrudescence within 28 days divided by total number of evaluable subjects.
Measured: 12 months
Safety and Tolerance
To determine the safety and tolerance of fosmidomycin and azothromycin when co-administered orally over three days. Safety and tolerability will be evaluated by the incidence, intensity, seriousness and relationship of new adverse event(s), and clinically relevant laboratory changes. The drug will be considered as safe if there are no serious adverse events attributable to the study drug.
Measured: 12 months
Day 7 cure rate of 100%
Efficacy of fosmidomycin and azithromycin when co-administered to adults with acute uncomplicated P.falciparum malaria.
Day 7 cure rate and Day 28 cure rates will be calculated from the following ratio: Number of subjects with clearance of asexual parasitaemia within seven days of commencement of treatment, without subsequent recrudescence within 28 days divided by total number of evaluable subjects.
Measured: 12 months
Secondary outcomes (2)
Blood samples at 0,1,2,3,4,6,8,12,14,18,24, 26,30,36,38,42,48,50,54,60,62,66,72,78,84,90,96,108,120,144.168.240 hours
pharmacokinetic profile. Full profiles of pharmacokinetic parameters including Cmax, Tmax, peak, trough, Vd, AUC, T1/2a, T1/2t, renal and total Cl will be derived.
Measured: 12 months
PCR corrected cure rates
to differentiate between reinfections and recrudescence
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2011 (estimated)
- Study startNov 2008
- Primary completionOct 2009
- Study completionDec 2011 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jomaa Pharma GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Mahidol University, Thammasat University
- Responsible party
- Sponsor
- Investigators
- Srivicha Krudsood, Prof, Principal investigator, Mahidol University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01464125
- Sponsor's protocol ID
- JP011
- Acronym
- JP011
- Status last verified
- Oct 2011
- First submitted
- 26 Oct 2009
- Last updated
- 3 Nov 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Fosmidomycin and Azithromycin When Administered Concurrently to Adult Subjects With Acute Uncomplicated Plasmodium Falciparum Malaria
- ClinicalTrials.gov ID
- NCT01464125
- Acronym / sponsor ID
- JP011 / JP011
- Conditions
- Malaria
- Keywords
- Malaria, Plasmodium falciparum, acute uncomplicated
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Jomaa Pharma GmbHIndustry (pharma, biotech, devices)
- Collaborators
- Mahidol University, Thammasat University
- Study start
- Nov 2008
- Primary completion
- Oct 2009 (actual)
- Study completion
- Dec 2011 (estimated)
- First posted
- 3 Nov 2011 (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 aim of this study is to evaluate the role of azithromycin as a possible combination partner for fosmidomycin to protect it from its susceptibility to recrudescent infections when used as monotherapy for acute Plasmodium falciparum malaria while retaining its excellent safety profile.
Detailed description
The scientific rationale for the use of this combination is to inhibit the ability of the parasite to synthesise isoprenoids, as precursors of many essential compounds including sterols, carotenoids and ubiquinones. This is effected through blockade of the non-mevalonate pathway by fosmidomycin as a potent inhibitor of 1-deoxy-D-xylulose 5-phosphate reductoisomerase coupled with targeting of protein biosynthesis by azithromycin through binding to the 50S ribosomal subunit. This mode of action contrasts with the ability of the human host to utilise the mevalonate pathway for isoprenoid synthesis and accounts for the safety profiles of both drugs through the mechanism of selective toxicity. Moreover it affords protection against cross resistance with existing chemotherapeutic agents.
The dose of fosmidomycin, equivalent to 30mg/kg twice daily for three days, selected for evaluation in this proof of concept study is derived from the highest dose that was administered in the Phase I safety tolerance studies. While the recommended dose of azithromycin for the treatment of bacterial infections is 250mg daily for three days, higher doses of up to 1500mg daily for three days have been evaluated for the treatment of malaria, in combination with artesunate or quinine.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fos-Azi | Experimental | Drug: Fosmidomycin, Drug: AzithromycinOpen label single arm concurrent administration of fosmidomycin and azithromycin. |
Who may qualify
- Ages
- 15 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- male and female subjects aged 15 to 55 years
- body mass index ≥ 18.5kg/M2
- uncomplicated P falciparum malaria with acute manifestations
- asexual parasitaemia between 500uL and 100,000uL
- ability to tolerate oral therapy
Key exclusion criteria (8 listed)
- signs of severe malaria, according to WHO criteria
- body mass index ≤ 18.5 kg/M2
- pregnancy by history or by positive urine test
- lactation
- mixed plasmodial infection
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 |
|---|---|---|
| FosmidomycinFosmidomycin sodium capsules 450 mg x 4 twelve-hourly for three days | Drug | Fos-Azi |
| AzithromycinAzithromycin capsules 250 mg x 3 twelve-hourly for three days | Drug | Fos-Azi |
Primary outcome
day 28 cure rate of >95%
Time frame: 12 months
Efficacy of fosmidomycin and azithromycin when co-administered to adults with acute uncomplicated P.falciparum malaria. Day 7 cure rate and Day 28 cure rates will be calculated from the following ratio: Number of subjects with clearance of asexual parasitaemia within seven days of commencement of treatment, without subsequent recrudescence within 28 days divided by total number of evaluable subjects.
Safety and Tolerance
Time frame: 12 months
To determine the safety and tolerance of fosmidomycin and azothromycin when co-administered orally over three days. Safety and tolerability will be evaluated by the incidence, intensity, seriousness and relationship of new adverse event(s), and clinically relevant laboratory changes. The drug will be considered as safe if there are no serious adverse events attributable to the study drug.
Day 7 cure rate of 100%
Time frame: 12 months
Efficacy of fosmidomycin and azithromycin when co-administered to adults with acute uncomplicated P.falciparum malaria. Day 7 cure rate and Day 28 cure rates will be calculated from the following ratio: Number of subjects with clearance of asexual parasitaemia within seven days of commencement of treatment, without subsequent recrudescence within 28 days divided by total number of evaluable subjects.
2 secondary outcomes
Blood samples at 0,1,2,3,4,6,8,12,14,18,24, 26,30,36,38,42,48,50,54,60,62,66,72,78,84,90,96,108,120,144.168.240 hours
Time frame: 12 months
PCR corrected cure rates
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2011.
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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.
Srivicha Krudsood, Prof principal investigator
Mahidol University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fosmidomycin and Azithromycin in people with Malaria, run by Jomaa Pharma GmbH at 1 site 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 6 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 3 Nov 2011. 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 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?
Results are not available in the source record.
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?
day 28 cure rate of >95% (time frame: 12 months). The study lists 3 primary outcomes in all. 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 3 Nov 2011.