A Crossover Bioavailability Clinical Trial of Parenteral Pyronaridine and Artesunate

NCT05929157 | Unknown Phase 1

• 1 other identifier: parP&A_22_1
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Severe Malarial Treatment

Outcome Measures

Primary Outcomes (3)

• Safety of injectable artesunate-pyronaridine

  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

  within the two week post injection

• Plasma level of Pyronaridine

  Change in concentration of post IV/IM injection whole blood and plasma level of Pyronaridine will be summarized over time

  iwithin the two week post injection

• Plasma level of Artesunate/dihydroartemisinin

  Change in concentration of post IV/IM injection plasma level of Artesunate/dihydroartemisinin will be summarized over time

  within the two week post injection

Secondary Outcomes (2)

• Pyronaridine area under the curve

  within the two week post injection

• Artesunate/dihydroartemisinin area under the curve

  within the two week post injection

Other Outcomes (2)

• Pyronaridine distribution

  within the two week post injection

• Pyronaridine metabolites

  within the two week post injection

Study Arms (2)

Artesunate-pyronaridine intravenous

ACTIVE COMPARATOR

Drug: artesunate-pyronaridine

Artesunate-pyronaridine intramuscular

ACTIVE COMPARATOR

Drug: artesunate-pyronaridine

Interventions

artesunate-pyronaridine 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; Artesunate-pyronaridine intravenous

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Centre de Recherche Médicale de Lambaréné: lead
• Institute of Tropical Medicine, University of Tuebingen: collaborator

Study Sites (1)

Centre de Recherches Médicales de Lammbaréné

Lambaréné, Moyen-Ogooué Province, 1437, Gabon

Location

MeSH Terms

Interventions

pyronaridine tetraphosphate, artesunate drug combination

Central Study Contacts

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

CONTACT

+24177406464; aadegnika@gmail.com

Diane Egger-Adam, Ph.D.

CONTACT

+49 7071 2982191; diane.egger-adam@uni-tuebingen.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Phase I monocentric clinical trial with a two-armed crossover design

Study Record Dates

• First Submitted: June 16, 2023
• First Posted: July 3, 2023
• Study Start: September 1, 2023
• Primary Completion: December 31, 2024
• Study Completion: June 30, 2025
• Last Updated: July 24, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

GA (1)