A Crossover Bioavailability Clinical Trial of Parenteral Pyronaridine and Artesunate

NCT ID: NCT05929157

Last Updated: 2023-07-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-01
• Study Completion Date: 2025-06-30

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.

Conditions

Severe Malarial Treatment

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Artesunate-pyronaridine intravenous

Group Type: ACTIVE_COMPARATOR

artesunate-pyronaridine

Intervention Type: DRUG

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.

Artesunate-pyronaridine intramuscular

Group Type: ACTIVE_COMPARATOR

artesunate-pyronaridine

Intervention Type: DRUG

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.

Interventions

artesunate-pyronaridine

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Institute of Tropical Medicine, University of Tuebingen

OTHER

Sponsor Role: collaborator

Centre de Recherche Médicale de Lambaréné

OTHER

Sponsor Role: lead

Responsible Party

Prof. Ayola Akim ADEGNIKA

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Centre de Recherches Médicales de Lammbaréné

Lambaréné, Moyen-Ogooué Province, Gabon

Countries

Gabon

Central Contacts

Ayola Akim Adegnika, M.D.; Ph.D.

Role: CONTACT

aadegnika@gmail.com

+24177406464

Diane Egger-Adam, Ph.D.

Role: CONTACT

diane.egger-adam@uni-tuebingen.de

+49 7071 2982191

Other Identifiers

parP&A_22_1

Identifier Type: -

Identifier Source: org_study_id