Triple Antimalarial Combination to Accelerate the Parasite Clearance and to Prevent the Selection of Resistant Parasites

Plasmodium Falciparum Malaria (Drug Resistant) Clinical Trial

— Artesynib  

Official title:

Triple Antimalarial Combination (Imatinib-DHA-PPQ) to Accelerate the Parasite Clearance and to Prevent the Selection of Resistant Parasites

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03697668
• Other study ID #: NUREX S.r.l
• Status: Recruiting
• Phase: Phase 2
• Start date: September 17, 2017
• Est. completion date: December 31, 2019

Study information

• Verified date: October 2018
• Source: Nurex S.r.l.
• Contact: Huynh D Chien, MD,PhD
• Phone: +84903580518
• Email: huynhdinhchien55[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to provide a new drug combination for a better treatment of P. falciparum for a faster parasite clearance and to counteract artemisinin resistance.

Description:

According to WHO, resistance to artemisinin derivatives (ART) is emerging in many areas of the Greater Mekong Region as a delayed parasite clearance following a standard treatment by artemisinin combined therapy (ACT). Artemisinin resistance is often accompanied by the resistance to the partner drugs such as piperaquine (PPQ), mefloquine (MEF), amodiaquine (AQ) and lumefantrine (LF).

The slow and incomplete clearance of parasites following ACT treatment is considered to permit the selection of resistant parasites.

The availability of new, more efficient treatments accelerating the clearance of parasites is therefore needed to counteract the selection of ART resistant strains.

Imatinib (IMA) has been demonstrated to increase the efficacy of ART in a synergic fashion. This positive effect is further potentiated by low concentrations of PPQ.

IMA is active both on the intra-erythrocyte asexual forms and on gametocytes. It is therefore expected that the combination DHA-PPQ-IMA should lead to faster and radical clearance of the parasites, therefore reducing the frequency of healthy carriers and transmission.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Patients diagnosed with mild to moderate P. falciparum malaria

2. Adult male, age 18-55 years

3. Good health conditions other than malaria

4. The patient did not take anti-malarial drugs in the past 4 weeks

Exclusion Criteria:

1. unable to provide Informed Consent or Patient History Form

2. symptoms and signs of severe or complicated malaria including: continuous high fever over 39 °C, confusion, convulsions

3. parasitemia<150.000 parasites /microliter

4. other neurological or psychiatric symptoms or disorders

5. abnormal bleeding

6. resting hearth rate lower than 60 and higher than 100 bpm

7. abnormal ECG, history of cardiac diseases

8. male adults with corrected QT intervals > 450ms

9. signs, symptoms and laboratory results of impairment of vital organs such as liver, lungs, kidney and cardiovascular system

10. hemoglobin < 9.0 gm/100ml

11. symptoms and signs of infection such as pneumonia, dengue fever, and other viral or bacterial infection.

12. patients with symptoms of gastrointestinal infections or any sign of malabsorption that may interfere with drug absorption

13. concomitant infection by plasmodium species other than P. falciparum

14. inability to meet daily with local doctor during period of clinical trial

15. concomitant medicines like:

1. medicines used to treat high cholesterol in the blood (such as atorvastatin, lovastatin, simvastatin);

2. medicines used to treat hypertension and heart problems (such as diltiazem, nifedipine, nitrendipine, verapamil, felodipine, amlodipine);

3. medicined used to treat HIV (antiretroviral medicines): protease inhibitors (such as amprenavir, atazanavir, indinavir, nelfinavir, ritonavir), non-nucleoside reverse transcriptase inhibitors (such as efavirenz, nevirapine);

4. medicines used to treat microbial infections (such as telithromycin, rifampicin, dapsone);

5. medicines used to help you fall asleep: benzodiazepines (such as midazolam, triazolam, diazepam, alprazolam), zaleplon, zolpidem;

6. medicines used to prevent/treat epileptic seizures: barbiturates (such as phenobarbital), carbamazepine or phenytoin;

7. medicines used after organ transplantation and in autoimmune diseases (such as cyclosporin, tacrolimus);

8. sex hormones, including those contained in hormonal contraceptives (such as gestodene, progesterone, estradiol), testosterone; - glucocorticoids (hydrocortisone, dexamethasone); - omeprazole (used to treat diseases related to gastric acid production);

9. paracetamol (used to treat pain and fever);

10. theophylline (used to improve bronchial air flow);

11. nefazodone (used to treat depression);

12. aprepitant (used to treat nausea);

Related Conditions & MeSH terms

• Malaria, Falciparum
• Plasmodium Falciparum Malaria (Drug Resistant)

Intervention

Drug:
• Imatinib
triple combination for the treatment of malaria
• Dihydroartemisinin-piperaquine
standard malaria treatment

Locations

Country	Name	City	State
Vietnam	A Tuc	Huong Hóa	Quang Tri

Sponsors (4)

Lead Sponsor	Collaborator
Nurex S.r.l.	Purdue University, Università degli Studi di Sassari, Vinmec Healthcare System

Country where clinical trial is conducted

Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of Adverse Events	Occurrence of Adverse Events over 42 days observation period	From baseline to day 42
Primary	Occurrence of Severe Adverse Events	Occurrence of Severe Adverse Events over 42 days observation period	From baseline to day 42
Primary	Occurrence of Abnormal Physical Symptoms	Occurrence of Abnormal Physical Symptoms (Clinical Abnormalities) over 42 days observation period	From baseline to day 42
Primary	Occurrence of Abnormal Laboratory Values	Occurrence of Abnormal Laboratory Values over 42 days observation period	From baseline to day 42
Secondary	Frequency of residual parasitemia: % of patients with >1000 parasites/ ul at day 3 and 28	Parasitemia is determined by assessing the parasite count in blood, using thin film, thick film and qPCR analysis.	day 3 and day 28
Secondary	Frequency of fever and malaria symptoms	Percentage of patients with fever or malaria symptoms observed at Phisical Visit at day 3 and 28.	day 3 and day 28
Secondary	Mean parasitemia in the control and investigational arms	Mean parasitemia by assessing the parasite count in blood, using thin film, thick film and qPCR analysis, expressed as parasites / ul at day 2, 3 and 5 measured in the control and investigational arms	day 2 and day 5
Secondary	Parasite half-life measured at 12 and 24 hours	Mean parasite clearance half-life calculated using parasitemia measured at baseline, 12 and 24 hours post-treatment	from baseline to 24 hours post-treatment