Single-dose oral bioequivalence study of primaquine phosphate tablets USP 15 mg (test) and primaquine 15 mg tablet (reference) in healthy adult human subjects under fasting conditions

Primaquine (PQ) or PQ phosphate is a drug that was developed in the 1950s by the US army that is used to prevent relapse in Plasmodium vivax and P. ovale malaria and has been recommended for many years by the WHO for blocking the transmission of P. falciparum malaria.
There is now a growing interest in single low-dose PQ for blocking the transmission of Plasmodium falciparum, following the WHO’s recommendation in 2012. WHO recommends the use of a single 0.25-mg/kg dose of PQ in combination with standard artemisinin-based combination therapy (ACT) for the treatment of P. falciparum malaria in elimination and resistance containment settings. Several trials have shown that single low-dose primaquine reduced mosquito infectivity.
Children are disproportionally affected by malaria of which vivax malaria affects young children less than 15 years of age, peaking between 2 and 6 years, which carries the highest risk of illness and death. Children under the age of 5 years accounted for 67% of deaths from malaria in the African region in 2019.
However, there are no paediatric PQ formulations that are friendly to children. The availability of paediatric drugs in the right dosage forms with acceptable taste and odour/flavour is critically important for increasing adherence and allowing PQ regimens that do not need tablet fractions or require crushing tablets.
PQ is now considered essential for eliminating malaria but to ensure child-friendly PQ is made available it either has to be WHO prequalified or registered with a stringent drug regulatory authority.
WHO prequalification offers the possibility of a line extension based on demonstrating proportionality with the adult 15 mg tablet. For a generic manufacturer, a bioequivalence study must be performed comparing the generic (test) product with the reference 15 mg of primaquine.
This study is to establish the bioequivalence of a new scored 15 mg generic PQ tablet, produced by IPCA in India. The study will be conducted to international standards, following WHO guidelines and other applicable requirements.

Study design: Open-label randomized two-period two-treatment two-sequence crossover balanced single-dose oral bioequivalence study

Primary study design: Interventional

Secondary study design: Randomised cross over trial

Condition: Bioequivalence study

International Standard Randomised Controlled Trial Number: ISRCTN54640699

Clinical trial registration

Drug-based Strategies

May 2021 — Jan 2023

India