A study of the effects of Coartem, Malarone and artesunate-mefloquine on auditory function in patients 12 years of age or older with acute uncomplicated P. falciparum malaria

• Register: EUCTR
• Last refreshed on: 4 September 2017
• Main ID: EUCTR2016-004321-16-Outside-EU/EEA
• Date of registration: 31/08/2017
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma AG
• Public title: A study of the effects of Coartem, Malarone and artesunate-mefloquine on auditory function in patients 12 years of age or older with acute uncomplicated P. falciparum malaria
• Scientific title: A study of the effects of Coartem, Malarone and artesunate-mefloquine on auditory function in patients 12 years of age or older with acute uncomplicated P. falciparum malaria
• Target sample size: 265
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004321-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Colombia

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

Key inclusion & exclusion criteria

Inclusion criteria:
Those patients who can be included in the study are:
1. Male and female adults and children = 12 years of age
2. With microscopic confirmed diagnosis of acute uncomplicated P. falciparum malaria or mixed infection including P. falciparum using Giemsa-stained thick film
3. With P. falciparum parasitemia of more than 1000 and less than 100,000 parasites/µL
4. With history of fever or presence of fever (tympanic or axillary temperature = 37.5°C)
5. Who have signed or finger marked an informed consent form (for children below age of consent, with an informed consent signed or finger marked by their legal guardian/caretaker)
Are the trial subjects under 18? yes
Number of subjects for this age range: 265
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 265
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Those patients who can be excluded in the study are:
1. Pregnant or lactating (urine test for ß-HCG to be performed on any woman of child bearing age)
2. With signs/symptoms indicative of severe/complicated malaria according to WHO
classification
3. History of any drug-related hearing impairment
4. Chronic underlying disease such as known positive HIV status, sickle cell disease, and
severe cardiac, renal, or hepatic impairment
5. Other serious physical conditions e.g. history of head or brain trauma, previous severe or
cerebral malaria, severe malnutrition, severe jaundice
6. Known history of psychiatric disorders or convulsions
7. Splenectomy
8. Family history of long QT syndrome or sudden death, or any other clinical condition
known to prolong the QTc interval, such as history of symptomatic cardiac arrhythmias,
clinically relevant bradycardia or severe heart disease
9. Known disturbances of electrolyte balance, e.g. hypokalaemia or hypomagnesaemia
10. History of hypersensitivity to any of the study drugs or to any of their excipients or to
chemically related compounds (e.g., for mefloquine, quinine and quinidine)
11. Severe vomiting and unable to tolerate oral treatment
12. Taking ingestion of any of the following drugs in the previous 2 months: mefloquine,
aminoglycoside antibiotics, halofantrine, artemether-lumefantrine
13. Taking ingestion of any of the following drugs in the previous 2 weeks: quinine,
chloroquine (or any other antimalarial drug), ASA (acetylsalicylic acid), loop diuretics,
macrolide antibiotics
14. Taking drugs that are known to influence cardiac function and to prolong the QTc
interval, such as class IA and III antiarrhythmics, neuroleptics, antidepressive agents and
certain antibiotics (including some agents in the following classes: macrolides,
fluoroquinolones, imidazoles and triazoles), antifungal agents, certain non-sedating
antihistamines (terfenadine, astemizole) and cisapride
15. Taking drugs metabolized by cytochrome CYP2D6 (e.g., flecainide, metoprolol,
imipramine, amitriptyline, clomipramine)
16. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 halflives of enrollment, whichever is longer Audiology testing specific exclusion criteria

• Current ear infections, ear discharge, prior middle ear or inner ear surgery, wearing a
hearing aid, or unable to cooperate with audiological testing.
• Cerumen completely or partially occluding the external auditory canal which cannot be
removed by a physician using a cerumen curette or a simple apparatus for ear canal
irrigation with mineral oil.
• Abnormal tympanometry in either or both ears defined as Type B (“flat”, static
compliance peak equal or less than 0.20 cm3) or Type C (“negative”) with peak pressure >
-120 dPA. Normal static compliance is between 0.3 and 1.4 cm3.




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

This study assessed the effects of artemether-lumefantrine on the auditory nerve pathway as assessed by Auditory Brainstem Response (ABR) and audiometric testing in acute uncomplicated Plasmodium falciparum malaria in patients 12 years of age or older.

Therapeutic area: Diseases [C] - Parasitic Diseases [C03]

Intervention(s)

Trade Name: Coartem/Riamet
Product Name: Riamet
Product Code: COA566
Pharmaceutical Form: Tablet
INN or Proposed INN: ARTEMETHER
CAS Number: 71963-77-4
Current Sponsor code: COA566
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
INN or Proposed INN: LUMEFANTRINE
CAS Number: 82186-77-4
Current Sponsor code: COA566
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 120-

Primary Outcome(s)

Primary end point(s): Rate of ABR Wave III latency changes of > 0.3 msec

Main Objective: To demonstrate the safety of artemether-lumefantrine after 3 days of treatment in patients with acute, uncomplicated P. falciparum malaria by testing the null hypothesis that the rate of auditory brainstem pathway abnormalities is >= 15% in the population treated with artemether-lumefantrine, as assessed by ABR at Day 7 following initiation of treatment compared with their baseline values. An “auditory brainstem pathway abnormality” is here defined as a greater than 0.30 msec change in Wave III latency from baseline to Day 7.

Secondary Objective: – To evaluate the safety of artemether-lumefantrine after 3 days of treatment in patients with acute, uncomplicated P. falciparum malaria by determining the descriptive changes from baseline in auditory function, evaluated by audiometric measurements at Day 3, 7, 28, and 42 following initiation of treatment.
- To evaluate the efficacy by PCR adjusted malaria cure rates of the three treatment regimen at Days 14, 28, and 42, defined as the proportion of patients with clearance of asexual parasitemia within 7 days of initiation of trial treatment, without recrudescence within 14, 28 and 42 days, respectively, after initiation of treatment.

Timepoint(s) of evaluation of this end point: Baseline, Day 3, Day 7, Day 28, Day 42

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Baseline and Days 14, 28 and 42

Secondary end point(s): PCR adjusted malaria cure rates

Secondary ID(s)

CCOA566A2417

Source(s) of Monetary Support

Novartis Investigative Site