Clinical trial NCT05929157: A Crossover Bioavailability Clinical Trial of Parenteral Pyronaridine and Artesunate
Official title: A Crossover Bioavailability Clinical Trial of Parenteral Pyronaridine and Artesunate
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Severe Malarial Treatment
Lead sponsor: Centre de Recherche Médicale de Lambaréné
Sponsor class: OTHER
Collaborators: name: Institute of Tropical Medicine, University of Tuebingen
First posted: 2023-07-03
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Phase I monocentric clinical trial with a two-armed crossover design
Primary purpose: OTHER

Brief summary: The clinical trial is a Phase I monocentric clinical trial with a two-armed crossover design to evaluate the bioavailability of parenteral Pyronaridine and Artesunate.

Pyronaridine and Artesunate are antimalarial agents with a history of clinical use, and Artesunate has been used clinically in combination with other drugs also. The action of Artesunate is a rapid knock down of the parasites, after which, the drug is quickly cleared as it has a short systemic half-life. Pyronaridine is also rapidly effective in the short term but has a long blood half-life thus providing a more sustained schizonticidal effect.

12 study subjects will be included into the clinical trial after having signed the informed consent, being screened and judged to be eligible. 6 of them (group 1) will, on Day 0, be injected intravenously with 4 mg base/kg of Pyronaridine together with 4 mg/kg of Artesunate. The group 2 (the other 6 subjects) will on the same day (Day 0) be injected intramuscularly with the 4 mg base/kg of Pyronaridine together with 4 mg/kg of Artesunate (into separate sites) 8 weeks later group 1 will be injected intramuscularly with the same amount of Pyronaridine and Artesunate as on Day 0. Group 2 will also get the same amount as on Day 0 but this time the injection will be intravenously for group 2.

The primary objective is to assess the safety and tolerability by measuring (a) the proportion of subjects with adverse events (AEs) and serious adverse events (SAEs) throughout the study; (b) the proportion of subjects with solicited AEs 15 days after IMP injection; (c) the proportion of subjects with unsolicited AEs throughout the clinical trial. Further, the pharmacokinetics of both drugs will be determined.

Detailed description: The clinical trial is a Phase I monocentric clinical trial with a two-armed crossover design to evaluate the bioavailability of parenteral Pyronaridine and Artesunate.

Pyronaridine and Artesunate are antimalarial agents with a history of clinical use, and Artesunate has been used clinically in combination with other drugs also. The action of Artesunate is a rapid knock down of the parasites, after which, the drug is quickly cleared as it has a short systemic half-life. Pyronaridine is also rapidly effective in the short term but has a long blood half-life thus providing a more sustained schizonticidal effect.

12 study subjects will be included into the clinical trial after having signed the informed consent, being screened and judged to be eligible. 6 of them (group 1) will, on Day 0, be injected intravenously with 4 mg base/kg of Pyronaridine together with 4 mg/kg of Artesunate. The group 2 (the other 6 subjects) will on the same day (Day 0) be injected intramuscularly with the 4 mg base/kg of Pyronaridine together with 4 mg/kg of Artesunate (into separate sites) 8 weeks later group 1 will be injected intramuscularly with the same amount of Pyronaridine and Artesunate as on Day 0. Group 2 will also get the same amount as on Day 0 but this time the injection will be intravenously for group 2.

The primary objective is to assess the safety and tolerability by measuring (a) the proportion of subjects with adverse events (AEs) and serious adverse events (SAEs) throughout the study; (b) the proportion of subjects with solicited AEs 15 days after IMP injection; (c) the proportion of subjects with unsolicited AEs throughout the clinical trial. Further, the pharmacokinetics of both drugs will be determined.

Eligibility criteria: Inclusion Criteria:

* Male and female volunteers aged 18-45 years with an asymptomatic Plasmodium falciparum infection.
* Able and willing (in the investigator's opinion) to comply with all trial requirements.
* General good health based on medical history and clinical examination.
* Written informed consent.
* Available to participate in follow-up for the duration of the trial (4 months in total).
* Reachable by phone during the whole trial period.
* Women only: Must agree to practice continuous effective contraception for the duration of the trial.

Exclusion Criteria:

* Pregnancy, lactation, or intention to become pregnant during the trial.
* Known HIV-, HBV- and HCV-infection.

Primary outcomes:
measure: Safety of injectable artesunate-pyronaridine
timeFrame: within the two week post injection
measure: Plasma level of Pyronaridine
timeFrame: iwithin the two week post injection
measure: Plasma level of Artesunate/dihydroartemisinin
timeFrame: within the two week post injection
Secondary outcomes:
measure: Pyronaridine area under the curve
timeFrame: within the two week post injection
measure: Artesunate/dihydroartemisinin area under the curve
timeFrame: within the two week post injection
Other outcomes:
measure: Pyronaridine distribution
timeFrame: within the two week post injection
measure: Pyronaridine metabolites
timeFrame: within the two week post injection
Locations:
city: Lambaréné
country: Gabon
facility: Centre de Recherches Médicales de Lammbaréné
state: Moyen- Ogooué
Study officials:
References: