Healthy
Conditions
Keywords
Healthy, L-PZQ, PZQ, MSC2499550A, Praziquantel
Brief summary
The primary objective of the trial is to compare the overall palatability of the new orally disintegrating L-Praziquantel (L-PZQ ODT), the new racemate PZQ ODT (Rac-PZQ ODT) and the current available racemate PZQ tablets (reference) as assessed by means of human gustatory sensation tests (100 millimeter \[mm\] visual analogue scale \[VAS\] scoring modified by the incorporation of a 5 point facial hedonic scale). The secondary objectives are * To obtain feedback from children regarding the taste of different formulations using an open ended questionnaire * To document any discomfort or other observation in relation to acceptance of the study medication
Detailed description
Initially pupils will be invited with their parents to school where they will be asked to give consent/assent in to the study and they will be instructed on how to follow up the taste study procedures. Enrollments will occur in the health facilities in Ikwiriri/Kibiti at the end of successive training. Informed consent from parents and guardians and assent from the child will be obtained before participation in the study. The study will be conducted in school children 6 years and older as recommended by the Committee for medical product for human use (CHMP) reflection paper: formulations of choice for the pediatric population. -This is a randomized, five-period cross over, single center swill and spit taste study where the drug will not be swallowed but will be spit out after tasting. On Day 1, the subjects will assess the palatability of the following arms in a randomized sequence: * L-PZQ ODT (150 mg) put and disintegrated in the mouth * Rac- PZQ ODT (150 mg) put and disintegrated in the mouth On Day 2, the subjects will assess the palatability of the following arms in a randomized sequence: * L-PZQ ODT (150 mg) dispersed in water administered in the mouth cavity * Rac- ODT (150 mg) dispersed in water administered in the mouth cavity * 150 mg current PZQ tablet (1/4 of a 600 mg tablet) crushed, dispersed in water and administered in the mouth cavity Gustatory sensation studies will be performed on the different formulations immediately after tasting and 2-5 min after the study drug has been spat out. All volunteers will be asked to place a mark along the line with the use of a 100 mm visual analogue scale (VAS) that incorporates a 5 points hedonic scale for overall palatability. In addition, any discomfort or other observation in relation to acceptance of the study medication (Example: spitting out of the medicine) will be reported by the parents or investigator. An open ended questionnaire (description of mouth feeling and taste description) will be conducted for each child during the washout period. After the trial a therapeutic dose of Praziquantel will be made available to the local health council and management team to provide to the participating school.
Interventions
DRUGL-PZQ ODT
L-PZQ ODT (MSC2499550A) tablet at a dose of 150 milligram (mg) put and disintegrated in the mouth without water
DRUGRac-PZQ ODT
Rac-PZQ ODT (MSC1028703A) tablet at a dose of 150 mg put and disintegrated in the mouth without water
DRUGCesol®
Cesol® tablet at a dose of 150 mg crushed in water
Sponsors
Swiss Tropical & Public Health Institute
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 11 Years
Healthy volunteers
Yes
Inclusion criteria
1. Children male or female aged 6-11 years (inclusive) 2. Parents or guardians gave written informed consent prior to any trial related procedure and child gave assent 3. Able to communicate well with the Investigator, understanding the protocol requirements and restrictions, and willing to comply with the requirements of the entire trial 4. Subjects should be able to hold 2 milliliter (mL) of any appropriate juice in their mouth for 10 seconds without swallowing it and to keep a candy in the mouth for 20 seconds without swallowing it 5. Children who are able to properly assess and differentiate flavours of different soft drinks 6. Children who are able to use a hedonic scale (children were trained before the study)
Exclusion criteria
1. Unlikely to comply with the protocol requirements, instructions and trial-related restrictions, example: uncooperative attitude, inability to return for follow-up visits, and improbability of completing the trial 2. Children with any condition or dietary habit known to interfere with the sense of smell and taste, ingestion of any medication (except paracetamol) 3. Children with significant illness in the previous 2 weeks 4. Any surgical or medical condition, or any significant disease that in the opinion of the investigator, constitutes a risk or a contraindication for the participation of the subject in the study that could interfere with the study objectives, conduct or evaluation 5. Children who have participated in any clinical investigation within the previous 4 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Palatability Visual Analogue Scale (VAS) Score at 0 Minute (Right After the Spit-out of the Investigational Medicinal Product [IMP]) | 0 minute (Right After the Spit-out of the IMP) | Overall palatability was assessed on a 0 to 100 unit VAS scale, where higher scores indicate better palatability. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Palatability VAS Score at 2-5 Minutes | 2-5 minutes (After the IMP has been spat out) | Overall palatability was assessed on a 0 to 100 unit VAS scale, where higher scores indicate better palatability. |
| Number of Subjects With Mouth Feeling and Taste Description Evaluation | 2-5 minutes (After the IMP has been spat out) | Mouth feeling was described in terms of sweet, bitter, sticky or smooth as per the experience of the subject with the trial medication. |
| Number of Subjects With Discomfort or Observations Relating to Acceptance of the Study Medication | 2-5 minutes | — |
Countries
Tanzania
Participant flow
Pre-assignment details
This was a swill and spit taste study where the drug was not swallowed but spit out after tasting. Gustatory sensation tests were performed on the different formulations immediately after tasting and 2-5 min after the study drug has been spat out.
Participants by arm
| Arm | Count |
|---|---|
| L-PZQ Then Rac-PZQ (Day 1) L- Praziquantel (L-PZQ) 150 milligram (mg) oral disintegrating tablet (ODT) in first intervention period followed by racemate praziquantel (Rac-PZQ) 150 mg ODT in the second intervention period. A washout period of 1 hour was maintained between the intervention periods. The intervention was directly placed on the tongue of the subjects (without water) and the subjects were asked to spit out the tablet in a waste container. A mouth check was performed after the assessment to ensure that no particles remain in the oral cavity. | 24 |
| Rac-PZQ Then L-PZQ (Day 1) Rac-PZQ 150 mg ODT in first intervention period followed by L-PZQ 150 mg ODT in the second intervention period. A washout period of 1 hour was maintained between the intervention periods. The intervention was directly placed on the tongue of the subjects (without water) and the subjects were asked to spit out the tablet in a waste container. A mouth check was performed after the assessment to ensure that no particles remain in the oral cavity. | 24 |
| Total | 48 |
Baseline characteristics
| Characteristic | L-PZQ Then Rac-PZQ (Day 1) | Rac-PZQ Then L-PZQ (Day 1) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 24 Participants | 24 Participants | 48 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Gender Female | 12 Participants | 12 Participants | 24 Participants |
| Gender Male | 12 Participants | 12 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 48 | 1 / 48 | 0 / 47 | 0 / 47 | 0 / 47 |
| serious Total, serious adverse events | 0 / 48 | 0 / 48 | 0 / 47 | 0 / 47 | 0 / 47 |
Outcome results
Primary
Overall Palatability Visual Analogue Scale (VAS) Score at 0 Minute (Right After the Spit-out of the Investigational Medicinal Product [IMP])
Overall palatability was assessed on a 0 to 100 unit VAS scale, where higher scores indicate better palatability.
Time frame: 0 minute (Right After the Spit-out of the IMP)
Population: The Safety Set (SAF) included all enrolled subjects who received at least 1 dose of any study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| L-PZQ (Without Water) Day 1 | Overall Palatability Visual Analogue Scale (VAS) Score at 0 Minute (Right After the Spit-out of the Investigational Medicinal Product [IMP]) | 49.0 units on a scale | Standard Deviation 33.65 |
| Rac-PZQ (Without Water) Day 1 | Overall Palatability Visual Analogue Scale (VAS) Score at 0 Minute (Right After the Spit-out of the Investigational Medicinal Product [IMP]) | 39.3 units on a scale | Standard Deviation 28.43 |
| L-PZQ (With Water) Day 2 | Overall Palatability Visual Analogue Scale (VAS) Score at 0 Minute (Right After the Spit-out of the Investigational Medicinal Product [IMP]) | 67.5 units on a scale | Standard Deviation 31.14 |
| Rac-PZQ (With Water) Day 2 | Overall Palatability Visual Analogue Scale (VAS) Score at 0 Minute (Right After the Spit-out of the Investigational Medicinal Product [IMP]) | 51.4 units on a scale | Standard Deviation 32.35 |
| Cesol® (With Water) Day 2 | Overall Palatability Visual Analogue Scale (VAS) Score at 0 Minute (Right After the Spit-out of the Investigational Medicinal Product [IMP]) | 20.3 units on a scale | Standard Deviation 24.91 |
Secondary
Number of Subjects With Discomfort or Observations Relating to Acceptance of the Study Medication
Time frame: 2-5 minutes
Population: The Safety Set (SAF) included all enrolled subjects who received at least 1 dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| L-PZQ (Without Water) Day 1 | Number of Subjects With Discomfort or Observations Relating to Acceptance of the Study Medication | 0 Subjects |
| Rac-PZQ (Without Water) Day 1 | Number of Subjects With Discomfort or Observations Relating to Acceptance of the Study Medication | 0 Subjects |
| L-PZQ (With Water) Day 2 | Number of Subjects With Discomfort or Observations Relating to Acceptance of the Study Medication | 2 Subjects |
| Rac-PZQ (With Water) Day 2 | Number of Subjects With Discomfort or Observations Relating to Acceptance of the Study Medication | 0 Subjects |
| Cesol® (With Water) Day 2 | Number of Subjects With Discomfort or Observations Relating to Acceptance of the Study Medication | 0 Subjects |
Secondary
Number of Subjects With Mouth Feeling and Taste Description Evaluation
Mouth feeling was described in terms of sweet, bitter, sticky or smooth as per the experience of the subject with the trial medication.
Time frame: 2-5 minutes (After the IMP has been spat out)
Population: The data for this outcome measure could not be evaluated as data were not collected according to protocol.
Secondary
Overall Palatability VAS Score at 2-5 Minutes
Overall palatability was assessed on a 0 to 100 unit VAS scale, where higher scores indicate better palatability.
Time frame: 2-5 minutes (After the IMP has been spat out)
Population: The Safety Set (SAF) included all enrolled subjects who received at least 1 dose of any study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| L-PZQ (Without Water) Day 1 | Overall Palatability VAS Score at 2-5 Minutes | 50.7 units on a scale | Standard Deviation 27.23 |
| Rac-PZQ (Without Water) Day 1 | Overall Palatability VAS Score at 2-5 Minutes | 45.1 units on a scale | Standard Deviation 29.62 |
| L-PZQ (With Water) Day 2 | Overall Palatability VAS Score at 2-5 Minutes | 61.1 units on a scale | Standard Deviation 21.19 |
| Rac-PZQ (With Water) Day 2 | Overall Palatability VAS Score at 2-5 Minutes | 50.2 units on a scale | Standard Deviation 25.92 |
| Cesol® (With Water) Day 2 | Overall Palatability VAS Score at 2-5 Minutes | 33.5 units on a scale | Standard Deviation 22.23 |