Clinical Trial Results:
Open-label Investigation of the Pharmacokinetic (PK) Profile, Safety, Tolerability, and Efficacy of Multiple Administrations of Tapentadol Oral Solution Used for Treatment of Acute Pain in Children Aged 2 Years to Less Than 7 Years.
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Summary
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EudraCT number |
2019-000205-77 |
Trial protocol |
PL |
Global end of trial date |
06 Aug 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Jan 2021
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First version publication date |
08 Jan 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
KF5503-75
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
U1111-1225-7869 | ||
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Sponsors
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Sponsor organisation name |
Grünenthal GmbH
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Sponsor organisation address |
Zieglerstr. 6, Aachen, Germany, 52099
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Public contact |
Grünenthal Trial Information Desk, Grünenthal GmbH, 49 2415693223, Clinical-Trials@grunenthal.com
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Scientific contact |
Grünenthal Trial Information Desk, Grünenthal GmbH, 49 2415693223, Clinical-Trials@grunenthal.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
26 Aug 2020
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Aug 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To investigate the Pharmacokinetic (PK) profile of tapentadol after the administration of multiple doses of tapentadol oral solution to children aged 2 years to less than 7 years after a painful event that routinely produces acute pain requiring treatment with a strong analgesic medication (e.g., opioids or metamizole).
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Protection of trial subjects |
The trial was conducted according to Good Clinical Practice guidelines, the applicable local laws, and in accordance with the ethical principles that have their origins in the Declaration of Helsinki. The competent authority approved the trial as required by national regulations. The regulatory authority was notified of the trial and amendments as required by national regulations. Tapentadol oral solution was administered to pediatric subjects in accordance with the approved SmPC for the pediatric population. Assessments/interventions have been limited as far as possible to those that would be performed according to the standard of care. Subjects were hospitalised during the entire treatment and evaluation phase to ensure the medical status of each subject was regularly and carefully monitored by qualified medical professionals. Vital signs (respiratory rate, blood pressure, and heart rate) and oxygen saturation (by pulse oximetry) were monitored as per local standard of care from before the administration of Dose 1 until the end of Visit 3. Vital signs and oxygen saturation values were recorded at specified time points before each investigational medicinal product administration and PK blood sampling.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Sep 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 10
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Worldwide total number of subjects |
10
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EEA total number of subjects |
10
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
10
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 3 sites in Poland between 9 September 2019 and 06 August 2020. | ||||||
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Pre-assignment
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Screening details |
A total of 10 subjects were enrolled and treated in the study. | ||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Tapentadol Oral Solution | ||||||
Arm description |
Subjects received a target dose of 1.25 milligram (mg) tapentadol per kilogram (kg) body weight every 4 hours (± 15 minutes), in 1 of 2 available concentrations. Subjects with body weight less than or equal to (<=) 16 kg received tapentadol oral solution 4 milligram per milliliter (mg/mL); whereas subjects with body weight greater than (>)16 kg received tapentadol oral solution 20 mg/mL. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Tapentadol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects with body weight <=16 kg received tapentadol oral solution 4 mg/mL; whereas subjects with body weight >16 kg received tapentadol oral solution 20 mg/mL.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
Subjects received a target dose of 1.25 mg tapentadol per kg body weight every 4 hours (± 15 minutes), in 1 of 2 available concentrations. Subjects with body weight <= 16 kg received tapentadol oral solution 4 mg/mL; whereas subjects with body weight >16 kg received tapentadol oral solution 20 mg/mL. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Tapentadol Oral Solution
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Reporting group description |
Subjects received a target dose of 1.25 milligram (mg) tapentadol per kilogram (kg) body weight every 4 hours (± 15 minutes), in 1 of 2 available concentrations. Subjects with body weight less than or equal to (<=) 16 kg received tapentadol oral solution 4 milligram per milliliter (mg/mL); whereas subjects with body weight greater than (>)16 kg received tapentadol oral solution 20 mg/mL. | ||
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End point title |
Area Under the Concentration-Time Curve at Steady State for the Dosing Interval (AUCtau,SS) for Tapentadol [1] | ||||||||
End point description |
AUCtau,SS was defined as area under the concentration-time curve at steady state for the dosing interval. The endpoint of this trial was estimated based on a population PK (popPK) model and the observed concentration-time data. The concentration data of all subjects who had a quantifiable serum concentration of tapentadol were analysed. The descriptive statistics presented for the endpoint include all evaluable subjects as per trial protocol.
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End point type |
Primary
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End point timeframe |
Four-hour dosing interval at steady-state
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Nonlinear mixed effects modeling approach using the first-order method with conditional estimation and interaction was applied to develop a popPK model based on the observed concentration-time data. The model was used to provide estimates of population and individual PK parameters and to simulate full multiple-dose concentration-time profiles for each subject based on the Empirical Bayes Estimates.The AUCtau,SS was calculated from the individual full profiles using the linear trapezoidal method. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Area Under the Concentration-Time Curve at Steady State for the Dosing Interval (AUCtau,SS) for Tapentadol-O-Glucuronide | ||||||||
End point description |
Tapentadol-O-Glucuronide was the metabolite of Tapentadol. AUCtau,SS was defined as area under the concentration-time curve at steady state for the dosing interval. The endpoint of this trial was estimated based on a popPK model and the observed concentration-time data. The concentration data of all subjects who had a quantifiable serum concentration of tapentadol-O-glucuronide were analysed. The descriptive statistics presented for the endpoint include all evaluable subjects as per trial protocol.
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End point type |
Secondary
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End point timeframe |
Four-hour dosing interval at steady-state
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| No statistical analyses for this end point | |||||||||
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End point title |
Area Under the Concentration-Time Curve at Steady State for the Dosing Interval (AUCtau,SS) for Tapentadol-O-Sulphate | ||||||||
End point description |
Tapentadol-O-Sulphate was the metabolite of Tapentadol. AUCtau,SS was defined as area under the concentration-time curve at steady state for the dosing interval. The endpoint of this trial was estimated based on a popPK model and the observed concentration-time data. The concentration data of all subjects who had a quantifiable serum concentration of tapentadol-O-sulphate were analysed. The descriptive statistics presented for the endpoint include all evaluable subjects as per trial protocol.
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End point type |
Secondary
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End point timeframe |
Four-hour dosing interval at steady-state
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Any adverse event (AE) that occurred between Dose 1 (included) until final dose + 48 hours (included), i.e. treatment emergent AE.
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Adverse event reporting additional description |
Reported AE were treatment emergent AEs i.e. any AE that occurred between Dose 1 until final dose + 48 hour (included). Analysis was performed on safety analysis set that included all subjects with at least 1 investigational medicinal product administration.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
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Reporting groups
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Reporting group title |
Tapentadol Oral Solution
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Reporting group description |
Subjects received a target dose of 1.25 mg tapentadol per kg body weight every 4 hours (± 15 minutes), in 1 of 2 available concentrations. Subjects with body weight <= 16 kg received tapentadol oral solution 4 mg/mL; whereas subjects with body weight >16 kg received tapentadol oral solution 20 mg/mL. | ||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
