Safety, Tolerability, Pharmacokinetics and Efficacy of ARCO

NCT01930331 | Completed Phase 4 DMC

• 1 other identifier: IHI
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Plasmodium Falciparum; Malaria, Falciparum

Keywords

Uncomplicated Plasmodium falciparum Malaria

Outcome Measures

Primary Outcomes (1)

• Number of reported non serious and serious adverse events

  Up to 6 Weeks

Secondary Outcomes (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.

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

Other Outcomes (1)

• Frequency of abnormal safety laboratory parameters (hematology, clinical chemistry, urinalysis and coagulation) and clinical parameters (blood pressure, pulse rate, temperature)

  weekly up to 6 weeks

Study Arms (2)

ARCO treatment

EXPERIMENTAL

Patients 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.

Drug: artemisinin/naphthoquine

Eurartesim treatment

ACTIVE COMPARATOR

Patients 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.

Drug: dihydroartemisinin/piperaquine phosphate

Interventions

artemisinin/naphthoquine DRUG

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)).

Also known as: ARCO®

ARCO treatment

dihydroartemisinin/piperaquine phosphate DRUG

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.

Also known as: Eurartesim®

Eurartesim treatment

Eligibility Criteria

• Age: 6 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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 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).
• 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:
• i. 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.

Sponsors & Collaborators

• Ifakara Health Institute: lead

Study Sites (1)

Ifakara Health Institute

Bagamoyo, 74, Tanzania

Location

Related Publications (1)

• 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.

  PMID: 35465706 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

artemisinin; naphthoquine; artemisinin-naphthoquine combination; artenimol; piperaquine

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Salim Abdulla, MD, PhD

  Ifakara Health Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2013
• First Posted: August 28, 2013
• Study Start: January 7, 2014
• Primary Completion: July 27, 2014
• Study Completion: June 1, 2015
• Last Updated: March 14, 2018

Record last verified: 2018-03

Locations

TA (1)