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Plasmodium FalciparumPhase 4NCT01930331

Safety, Tolerability, Pharmacokinetics and Efficacy of ARCO

A Phase 4 study testing artemisinin/naphthoquine and dihydroartemisinin/piperaquine phosphate in people with Plasmodium Falciparum and Malaria, Falciparum, run by Ifakara Health Institute at 1 site in Tanzania.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Phase IV, single center, 2 arms randomized controlled, open label study. Study will be conducted over a period of 42 days to determine the safety, tolerability, pharmacokinetics and efficacy of ARCO. Read more about this study

Who is it for?
Ages 6 to 60 years
Conditions the study is for
Plasmodium Falciparum, Malaria, Falciparum
What is being tested?
artemisinin/naphthoquine and dihydroartemisinin/piperaquine phosphate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteTanzania
Study dates
7 Jan 2014to 1 Jun 2015
Phase
Phase 4
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 6 to 60 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Written informed consent, in accordance with local practice, provided by patient, for children it will provided by either parents or legal representative and in addition children will provide assent.
  • Male or female patients between the age of 6 and 60 years (both inclusive)
  • Body weight between 20 kg and 90 kg (both inclusive)
  • Presence of mono-infection with P. falciparum (1,000 to 100,000 asexual count/µl of blood) microscopically confirmed.
  • Fever, as defined by axillary temperature ≥ 37.5°C to ≤ 39.5°C
  • Ability to swallow oral medication
  • Ability and willingness to adhere to all study procedures and access health facilities.
  • Agree to undergo study related procedures including being hospitalized for minimum of 3 days (0,1 and 2), and a follow up of up to 42 days.

Who cannot join

  • Patients with signs and symptoms of severe/complicated malaria as described in the WHO guideline(Third Edition 2012) for management of severe malaria(6)(Appendix 1)
  • Mixed Plasmodial 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.
  • Severe diarrhoea defined as 3 or more watery stools per day.
  • Presence of other serious or chronic clinical condition requiring hospitalization.
  • Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, QTcF or QTcB interval greater than or equal to 450 msec), respiratory (including active tuberculosis), history of jaundice, hepatic, renal, gastrointestinal, immunological, neurological (including auditory), endocrine, infectious, malignancy, psychiatric, history of convulsions or other abnormality (including head trauma).
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  • Family history of sudden death or of congenital prolongation of the QT interval or any other clinical condition known to prolong the QT interval.
  • Known congenital prolongation of the QT-interval or any clinical condition known to prolong the QT interval.
  • History of symptomatic cardiac arrhythmias or with clinically relevant bradycardia.
  • Any predisposing cardiac conditions for arrhythmia such as severe hypertension, left ventricular hypertrophy (including hypertrophic cardiomyopathy) or congestive cardiac failure accompanied by reduced left ventricle ejection fraction.
  • Electrolyte disturbances, particularly hypokalaemia, hypocalcaemia or hypomagnesaemia.
  • Any treatment which can induce a lengthening of QT interval, such as:
  • Antiarrhythmics (e.g. amiodarone, disopyramide, dofetilide, ibutilide, procainamide, quinidine, hydroquinidine, sotalol) ii. Neuroleptics (e.g. phenothiazines, sertindole, sultopride, chlorpromazine, haloperidol, mesoridazine, pimozide, or thioridazine) iii. Antidepressive agents, certain antimicrobial agents, including agents of the following classes macrolides (e.g. erythromycin, clarithromycin), fluoroquinolones (e.g. moxifloxacin, sparfloxacin), imidazole and triazole antifungal agents, and also pentamidine and saquinavir iv. Certain non-sedating antihistamines (e.g. terfenadine, astemizole, mizolastine), cisapride, droperidol, domperidone, bepridil, diphemanil, probucol, levomethadyl, methadone, vinca alkaloids, arsenic trioxide
  • Known history of hypersensitivity, allergic or adverse reactions to artemisinin containing compounds, piperaquine or naphthoquine or to any of the excipients contained in ARCO and Eurartesim.
  • Antimalarial treatment with different antimalarial drugs as follows i. Piperaquine-based compound, mefloquine, naphthoquine or sulphadoxine/pyrimethamine (SP) within the previous 3 months, ii. Amodiaquine or chloroquine within the previous 6 weeks, and with quinine, halofantrine, lumefantrine-based compounds and iii. Any other antimalarial treatment, antibiotics with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones, and azithromycin) or any herbal products, within the past 14 days
  • Have received an investigational drug within the past 6 weeks.
  • Liver function tests:
  • If Total Bilirubin is normal, exclude the patient if liver function tests ASAT/ALAT ≥ 3xULN ii. If Total Bilirubin is > 1 and ≤ 1.5xULN, exclude the patient if ASAT/ALAT ≥2xULN.
  • Total Bilirubin >1.5xULN
  • Hb level below 9 g/dL.
  • Serum creatinine levels more than 2 times the upper limit of normal range in absence of dehydration. In case of important dehydration the creatinine should be lower than 2X ULN after oral/parenteral rehydration.
  • Female patients must be neither pregnant (as demonstrated by a negative serum pregnancy test) nor lactating, and must be willing to take measures not to become pregnant during the study period and safety follow-up period.
  • Previous participation in any malaria vaccine trial or received malaria vaccine in any other circumstance

Trial locations and contacts

1 site in 1 country.

Tanzania1 site

  • Ifakara Health Institute

    Bagamoyo, 74

Other trials in Tanzania

About this study

Official title: Safety, Tolerability, Pharmacokinetics and Efficacy, Phase Iv, Open Label Study of Fixed Arco® and Eurartesim® Therapies in Adults and Children With Uncomplicated P. Falciparum Malaria in Tanzania

Phase IV, single center, 2 arms randomized controlled, open label study. Study will be conducted over a period of 42 days to determine the safety, tolerability, pharmacokinetics and efficacy of ARCO.

Read the detailed description

Evaluation of safety and tolerability of the administration of ARCO and Eurartesim in terms of blood biochemistry, full blood count, ECG assessments, vital signs and adverse events profile in patients with uncomplicated P. falciparum malaria. Dihydroartemisinin/piperaquine will be used as comparator.

Being tested
artemisinin/naphthoquine, dihydroartemisinin/piperaquine phosphate
Keywords
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.

  • artemisinin/naphthoquineDrug

    Also called ARCO®

    Each tablet of ARCO (artemisinin/naphthoquine) contains 125 mg artemisinin and 50 mg of naphthoquine. The total dose for adults will be 1000mg of artemisinin and 400mg of naphthoquine in a fixed oral dose (ARCO tablet).

    The regimen for children will be calculated according to the body weight (20mg artemisinin + 8mg naphthoquine per kg body weight in a fixed oral dose(ARCO tablet)).

  • dihydroartemisinin/piperaquine phosphateDrug

    Also called Eurartesim®

    Eurartesim (dihydroartemisinin/piperaquine phosphate) is a fixed dose preparation with two dose-strengths (20 mg dihydroartemisinin and 160mg of piperaquine phosphate and 40mg dihydroartemisinin and 320mg of piperaquine phosphate. The regimen for patients with body weight of 36-75kg is three tablets of 40mg dihydroartemisinin and 320mg of piperaquine phosphate once daily for three consecutive days. Those beyond or below this range the regimen will be calculated based on the body weight.

Study groups in NCT01930331
Study groupRoleWhat they receive
ARCO treatmentExperimentalPatients in this treatment arm will receive on Day 0 a single dose of standard treatment of artemisinin/naphthoquine (in a fixed oral dose of ARCO tablets). Treatment will be given under supervision.
Receives: Drug: artemisinin/naphthoquine
Eurartesim treatmentActive comparatorPatients in this treatment arm will receive a dose of dihydroartemisinin/piperaquine phosphate (in a fixed oral dose of Eurartesim tablets) over three days (0,1,2). Treatment will be given under supervision.
Receives: Drug: dihydroartemisinin/piperaquine phosphate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of reported non serious and serious adverse events

    Measured: Up to 6 Weeks

Secondary outcomes (1)

  1. 12-lead ECG recordings: Heart rate, PR interval, QRS duration, QT interval, QTc (Fridericia and Bazett corrections), any T wave or U-wave morphology.

    For ARCO treatment arm (which will only receive a single dose of ARCO treatment), Holter recording will start 15 minutes before the dose of ARCO, and it will run continuously during 12 hours post dosing.

    For Eurartesim treatment arm (which will receive three daily doses of Euratertesim treatment), Holter recording will run for 15 minutes before the first dose, and then it will start again 15 minutes before the third dose (last dose) running continuously for 12 hours post dosing.

    Measured: Holter recording will run continuously during 12 hours after the last dose of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Aug 2013 (estimated)
  2. Study start7 Jan 2014
  3. Primary completion27 Jul 2014
  4. Study completion1 Jun 2015

Resources

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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01930331
Sponsor's protocol ID
IHI
Status last verified
Mar 2018
First submitted
9 Aug 2013
Last updated
14 Mar 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • Ali AM, Gausi K, Jongo SA, Kassim KR, Mkindi C, Simon B, Mtoro AT, Juma OA, Lweno ON, Gwandu CH, Bakari BM, Mbaga TA, Milando FA, Hamad A, Shekalaghe SA, Abdulla S, Denti P, Penny MA. Population Pharmacokinetics of Antimalarial Naphthoquine in Combination with Artemisinin in Tanzanian Children and Adults: Dose Optimization. Antimicrob Agents Chemother. 2022 May 17;66(5):e0169621. doi: 10.1128/aac.01696-21. Epub 2022 Apr 25.

    PubMed 35465706

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing artemisinin/naphthoquine and dihydroartemisinin/piperaquine phosphate in people with Plasmodium Falciparum and Malaria, Falciparum, run by Ifakara Health Institute at 1 site in Tanzania.

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 23 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 Mar 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 Tanzania. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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?

Number of reported non serious and serious adverse events (time frame: Up to 6 Weeks). 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 NCT01930331, 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 Mar 2018.

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