Plasmodium Falciparum MalariaPhase 3NCT01258049
Superiority of ArTiMist Versus Quinine in Children With Severe Malaria
A Phase 3 study testing Artemether Sublingual Spray and Quinine in people with Plasmodium Falciparum Malaria, run by Proto Pharma Ltd at 3 sites in 3 countries.
Trial summary
The purpose of this study is to demonstrate that ArTiMist (sublingual artemether spray) is better than intravenous quinine in reducing parasite counts by >= 90% within 24 hours after the start of treatment in children with severe malaria, or uncomplicated malaria with gastrointestinal complications Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Plasmodium Falciparum Malaria
- What is being tested?
- Artemether Sublingual Spray and Quinine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 151 participants
- Where
- 3 sitesin 3 countries
- Study dates
- Dec 2010to Sep 2012
- Phase
- Phase 3
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- The patient's legally acceptable representative has provided informed consent and the patient has assented (where relevant) to participation in the trial
- The patient is a child that weighs between 5.00 kg and 15.00 kg inclusive
- The patient has falciparum malaria as evidenced by thick or thin blood smears of ≥ 500 P Falciparum per mcl (patients with mixed infections may be included provided ≥ 500 P Falciparum per mcl)
- The patient has either:
- severe or complicated falciparum malaria as determined by the investigator based on the WHO criteria for severity, and/or
- uncomplicated falciparum malaria but is unable to tolerate oral medication as a result of gastrointestinal complications such as vomiting or diarrhoea.
Who cannot join
- The patient's legally acceptable representative does not provide informed consent for participation, or the child if capable, does not assent to participation in the trial.
- Ability to tolerate oral therapy
- Patient has received any antimalarial therapy within the 7 days prior to first study drug administration.
- Patient has evidence of significant co-infections (this does not include mixed Plasmodium infections).
- Patient has a contraindication, allergy or is otherwise intolerant to either artemether or quinine .
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
Burkina Faso1 site
Centre National de Recherche et de Formation sur le Paludisme (CNRFP)
Ouagadougou, 01 BP 2208
About this study
Official title: A Phase III, Randomised, Open Labelled, Active Controlled, Multi Centre, Superiority Trial of ArTiMist™ Versus Intravenous Quinine in Children With Severe or Complicated Falciparum Malaria, or Uncomplicated Falciparum Malaria With Gastrointestinal Complications.
The purpose of this study is to demonstrate that ArTiMist (sublingual artemether spray) is better than intravenous quinine in reducing parasite counts by >= 90% within 24 hours after the start of treatment in children with severe malaria, or uncomplicated malaria with gastrointestinal complications
Read the detailed description
Malaria causes significant morbidity and mortality in children in developing countries, despite the availability of highly effective antimalarial therapy. One of the key contributing factors is the delay in the initiation of treatment.
ArTiMist is a sublingual formulation of the established antimalarial treatment, artemether. In previous studies good bioavailability has been demonstrated. In an exploratory study (ART003) ArTiMist demonstrated a non statistically significant improvement of 26% (when compared to intravenous quinine) in the numbers of patients experiencing a parasite reduction of >= 90% within 24 hours of the initiation of treatment.
This Phase 3 study is being conducted to establish whether treatment with ArTiMist in children with severe falciparum malaria or uncomplicated falciparum malaria with gastrointestinal complications is at least 20% superior in providing parasitological success (defined as >= 90% reduction in parasite count at 24 hours after start of treatment) when compared to intravenous quinine.
- Conditions
- Plasmodium Falciparum Malaria
- Being tested
- Artemether Sublingual Spray, Quinine
- Keywords
- Plasmodium infections, Remittent fever, Artemether, Artemesinins, Quinine, Malaria, Protozoan infections, sublingual drug delivery, Parasitic disease, Antiprotozoan agents
- Medical subject headings
- Malaria, Falciparum, Malaria, Protozoan Infections, Parasitic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Artemether Sublingual SprayDrug
Also called ArTiMist
Artemether sublingual spray administered at 3 mg/kg (milligrams per kilogram) at specified timepoints
QuinineDrug
Quinine administered intravenously, 20 mg/kg loading dose followed by 10 mg/kg every eight hours
| Study group | Role | What they receive |
|---|---|---|
| ArTiMist | Experimental | Not described Receives: Drug: Artemether Sublingual Spray |
| Quinine | Active comparator | Not described Receives: Drug: Quinine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Parasitological Success (MITT)
Parasitological success defined as a reduction in parasite count of ≥ 90% of baseline at 24 hours after the first dose
Measured: 24 hours after start of treatment
Parasitological Success (PP)
Parasitological success defined as a reduction in parasite count of ≥ 90% of baseline at 24 hours after the first dose
Measured: 24 hours after start of treatment
Secondary outcomes (14)
Parasite Clearance Time (PCT) [MITT Population]
Parasite clearance time (PCT). Time in hours from the initiation of therapy until the first of two successive parasite negative smears (zero parasite counts) are obtained
Measured: 28 days after start of treatment
PCT 90 [MITT Population]
Time for parasite counts to fall by 90%
Measured: 28 days after start of treatment
PCT 50 [MITT Population]
Time for parasite counts to fall by 50%
Measured: 28 days after start of treatment
PRR 24 [MITT Population]
The percentage reduction in parasite counts 24 hours after first dose
Measured: 28 days after start of treatment
PRR 12 [MITT Population]
The percentage reduction in parasite counts 12 hours after first dose
Measured: 28 days after start of treatment
Fever Clearance Time (FCT)
Time in hours from the initiation of therapy until the disappearance of fever (tympanic temperature < 38.0) that lasted at least 24 hours.
Measured: 28 days after start of treatment
Complete Cure Rate
The complete resolution of clinical signs and symptoms, malaria-related laboratory abnormalities, and elimination of asexual parasites by Day 7, with no recurrence up to Day 28 (+/- 2 days), and the 48h parasite count to be < 25% of baseline with no clinical deterioration
Measured: 28 days after the start of treatment
Early Treatment Failure
Early treatment failure is indicated by one or more of the following:
- Parasite count on Day 2 > Day 0, irrespective of temperature
- Parasite count on Day 3 > 0 with tympanic temperature ≥ 38.0°C
- Parasite count on Day 3 ≥ 25% of baseline
- Administration of rescue antimalarial treatment
Measured: Three days after the start of treatment
Late Clinical Failure
- Signs of severe malaria on any day between Day 4 and Day 28 in the presence of parasitaemia, without previously meeting any of the criteria of early treatment failure
- Presence of parasitaemia and tympanic temperature ≥ 38.0°C (or history of fever), on any day between Day 4 and Day 28, without previously meeting any of the criteria of early treatment failure
Measured: 28 days after the start of treatment
Late Parasitological Failure
- Parasitaemia on any day from Day 7 to Day 28 and tympanic temperature ≤ 38.0°C
Measured: 28 days after the start of treatment
Time to Return to Full Consciousness
Time in hours to return to full consciousness (Blantyre Coma Scale = 5), if level of consciousness is reduced (Blantyre Coma Scale <5) prior to dosing or within 24hours of first dosing.
For the Blantyre Coma Scale
Total - maximum 5, eye movement - maximum 1, best motor response - maximum 2, best verbal response - maximum 2
Measured: 28 days after start of treatment
Time to Return to Normal Per os Status
Time in hours to return to normal per os status. Normal per os was when the investigator considered the patient to be able to eat and drink normally.
Measured: 28 days after start of treatment
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events, of Possible, Probably and Definite Causalities
Measured: 28 days after start of treatment
Number of Deaths or Neurological Sequelae at Day 28
Measured: 28 days after start of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2010 (estimated)
- Study startDec 2010
- Primary completionAug 2012
- Study completionSep 2012
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 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 151 participants (actual)
Sponsor and investigators
- Lead sponsor
- Proto Pharma Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Daryl Bendel, MBChB MFPM, Study chair, Xidea Solutions Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01258049
- Sponsor's protocol ID
- ART004
- Status last verified
- Jan 2014
- First submitted
- 9 Dec 2010
- Last updated
- 28 Feb 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Bendel D, Rulisa S, Ansah P, Sirima S. Efficacy of a novel sublingual spray formulation of artemether in African children with Plasmodium falciparum malaria. Antimicrob Agents Chemother. 2015 Nov;59(11):6930-8. doi: 10.1128/AAC.00243-15. Epub 2015 Aug 24.
PubMed 26303805