Comparative palatability of orally disintegrating tablets (ODTs) of Praziquantel (L-PZQ and Rac-PZQ) versus current PZQ tablet in African children: a randomized, single-blind, crossover study

Abstract

BackgroundPraziquantel (PZQ) is currently the only recommended drug for infection and disease caused by the species of schistosome infecting humans; however, the current tablet formulation is not suitable for preschool age children mainly due to its bitterness and the size of the tablet. We assessed the palatability of two new orally disintegrating tablet (ODT) formulations of PZQ.\n\nMethodsThis randomized, single-blind, crossover, swill-and-spit palatability study (NCT02315352) was carried out at a single school in Tanzania in children aged 6-11 years old, irrespective of schistosomiasis infection. Children were stratified according to age group (6-8 years or 9-11 years) and gender, then randomized to receive each formulation in a pre-specified sequence. Over 2 days, the children assessed the palatability of levo-Praziquantel (L-PZQ) ODT 150 mg and Racemate Praziquantel (Rac-PZQ) ODT 150 mg disintegrated in the mouth without water on the first day, and L-PZQ and Rac-PZQ dispersed in water and the currently available PZQ 600 mg formulation (PZQ-Cesol(R)) crushed and dispersed in water on the second day. The palatability of each formulation was rated using a 100 mm visual analogue scale (VAS) incorporating a 5-point hedonic scale, immediately after spitting out the test product (VASt=0 primary outcome) and after 2-5 minutes (VASt=2-5).\n\nFindingsIn total, 48 children took part in the assessment. Overall, there was no reported difference in the VASt=0 between the two ODT formulations (p=0.106) without water. Higher VASt=0 and VASt=2-5 scores were reported for L-PZQ ODT compared with Rac-PZQ ODT in older children (p=0.046 and p=0.026, respectively). The VASt=0 and VASt=2-5 were higher for both ODT formulations compared with the current formulation (p<0.001 for both time points). No serious adverse events were reported.\n\nInterpretationThe new paediatric-friendly formulations dispersed in water were both found to be more palatable than the existing formulation of PZQ. There may be gender and age effects on the assessment of palatability.\n\nFundingThis study was funded by Merck KGaA, Darmstadt, Germany and the Global Health Innovative Technology (GHIT) Fund (Grant nos. 2013-212).\n\nAuthor summarySchistosomiasis or Bilharzia is among top debilitating parasitic diseases in endemic developing countries. It presents in two forms of either urinary or intestinal form. The diseases mode of transmission is waterborne through contact with infested water. The main group being affected in developing countries are women and children due to their frequent contact with water. WHO introduced mass drug administration program whereby drugs are distributed in endemic communities to cut off the transmission of NTDs schistosomiasis included.\n\nPraziquantel is the sole drug for treatment of all forms of Schistosomiasis currently and it has still been proven to be highly efficacious. Preventive chemotherapy program of WHO uses the same drug as a prophylactic tool to control the disease.\n\nThe biggest challenge for this drug is its availability as a 600mg tablet with a slightly bigger size and unpleasant taste, especially for younger children. This makes uneasy administering the correct dosage of drug to school children while making preschoolers totally neglected.\n\nThis study was done as swill and spit exercise (drug was not ingested) to assess the new orally disintegrating isomers of Praziquantel, L-PZQ and Rac-PZQ which have been prepared as a 150mg tablet and improved taste as compared to the existing Praziquantel formulation. Findings from 48 African children showed that both new formulations are more palatable to younger children as compared to the existing Praziquantel formulation.\n\nThese results provide evidence for further evaluation of the clinical efficacy and tolerability of the newer formulations towards the introduction of paediatric friendly Praziquantel tablets for Schistosomiasis treatment.