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

Background: Praziquantel (PZQ) is currently the only recommended drug for infection and disease caused by the schistosome species that infects humans; however, the current tablet formulation is not suitable for pre-school age children mainly due to its bitterness and the large tablet size. We assessed the palatability of two new orally disintegrating tablet (ODT) formulations of PZQ.

Methodology: This 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, with or without schistosomiasis infection as this was not part of the assessment. 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) 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).

Principal findings: In 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 standard formulation (p<0.001 for both time points). No serious adverse events were reported.

Conclusions/significance: The new paediatric-friendly formulations dispersed in water were both found to be more palatable than the existing standard formulation of PZQ. There may be gender and age effects on the assessment of palatability. Further research is needed for assessing efficacy and tolerability of the newly ODTs Praziquantel drug in younger children.

Trial registration: The trial was registered on ClinicalTrials.gov (NCT02315352) and in the Pan African Clinical Trials Registry (PACTR201412000959159).

Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: Eric Huber (EH) is an employee of Swiss Tropical and Public Health Institute, Basel, Switzerland, associated with the University of Basel, Basel, Switzerland. Elly Kourany-Lefoll (EK) is an employee of Ares Trading S.A., Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany. Wilhelmina Bagchus (WB) is an employee of Merck Serono, Lausanne, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany. Deon Bezuidenhout (BD) is an employee of Merck (Pty) Ltd, Modderfontein, South Africa, which is an affiliate of Merck KGaA, Darmstadt, Germany. Brooke Hayward (BH) is an employee of EMD Serono, Inc., Rockland, Massachussets, USA, which is an affiliate of Merck KGaA, Darmstadt, Germany.

Figures

Fig 1. Flow diagram of participant distribution showing the number of participants assessed for eligibility enrolled and randomized.

Fig 2. 100 mm Hedonic VAS scale.

Fig 3. Boxplot of VAS scores (mm) for L-PZQ ODT and Rac-PZQ ODT without water at time 0 minutes, by gender and age.

Dark lines indicate median values; ’+’ indicate mean values; the boxes represent the middle 50% of data with the bottom and top of the box represent the first and third quartiles (interquartile range, IQR); the whisker lines above and below the boxes represented the largest and smallest values that are not considered to be outliers; outliers are values that are 1.5 times the IQR below the first quartile or above the third quartile and are denoted with an open circle.

Fig 4. Boxplot of VAS scores (mm) for L-PZQ ODT and Rac-PZQ ODT without water at time 2–5 minutes, by gender and age.

Dark lines indicate median values; ’+’ indicate mean values; the boxes represent the middle 50% of data with the bottom and top of the box represent the first and third quartiles (interquartile range, IQR); the whisker lines above and below the boxes represented the largest and smallest values that are not considered to be outliers; outliers are values that are 1.5 times the IQR below the first quartile or above the third quartile and are denoted with an open circle.

Fig 5. Boxplot of VAS scores (mm) for L-PZQ ODT (L) and Rac-PZQ ODT (R) dispersed with water and current PZQ-Cesol (C) crushed in water at time 0 minutes, by gender and age.

Dark lines indicate median values; ’+’ indicate mean values; the boxes represent the middle 50% of data with the bottom and top of the box represent the first and third quartiles (interquartile range, IQR); the whisker lines above and below the boxes represented the largest and smallest values that are not considered to be outliers; outliers are values that are 1.5 times the IQR below the first quartile or above the third quartile and are denoted with an open circle.

Fig 6. Boxplot of VAS scores (mm) for L-PZQ ODT (L) and Rac-PZQ ODT (R) dispersed with water and current PZQ-Cesol (C) crushed in water at time 2–5 minutes, by gender and age.

Dark lines indicate median values; ’+’ indicate mean values; the boxes represent the middle 50% of data with the bottom and top of the box represent the first and third quartiles (interquartile range, IQR); the whisker lines above and below the boxes represented the largest and smallest values that are not considered to be outliers; outliers are values that are 1.5 times the IQR below the first quartile or above the third quartile and are denoted with an open circle.