Trial Outcomes & Findings for Pharmacokinetic, Efficacy and Safety Study of Tapentadol Oral Solution in Children With Postoperative Pain (NCT NCT01729728)

Results Overview

Mean and Standard Deviation of Serum Concentrations of Tapentadol. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

86 participants

Primary outcome timeframe

up to 15 hours

Results posted on

2019-11-04

Participant Flow

The first participant was enrolled on the 15 Nov 2012 and the last participant completed the trial on the 24 Feb 2014.

Consent was obtained for 86 participants in the trial. 66 participants were allocated and received study drug (investigational medicinal product). Pharmacokinetic data was obtained for the planned 56 participants.

Participant milestones

Participant milestones
Measure	Adolescents Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight)	Older Children Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight)	Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight)
Overall Study STARTED	21	28	17
Overall Study COMPLETED	20	22	16
Overall Study NOT COMPLETED	1	6	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Adolescents Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight)	Older Children Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight)	Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight)
Overall Study Adverse Event	0	6	0
Overall Study Protocol Violation	1	0	1

Baseline Characteristics

Pharmacokinetic, Efficacy and Safety Study of Tapentadol Oral Solution in Children With Postoperative Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Adolescents n=21 Participants Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Older Children n=28 Participants Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Young and Very Young Children n=17 Participants Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Total n=66 Participants Total of all reporting groups
Age, Continuous	15.5 years STANDARD_DEVIATION 1.6 • n=5 Participants	8.3 years STANDARD_DEVIATION 1.6 • n=7 Participants	3.4 years STANDARD_DEVIATION 1.1 • n=5 Participants	9.3 years STANDARD_DEVIATION 4.9 • n=4 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	17 Participants n=7 Participants	8 Participants n=5 Participants	34 Participants n=4 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	11 Participants n=7 Participants	9 Participants n=5 Participants	32 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants	27 Participants n=7 Participants	15 Participants n=5 Participants	63 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment United States	21 participants n=5 Participants	28 participants n=7 Participants	17 participants n=5 Participants	66 participants n=4 Participants
Weight	61.30 kilograms STANDARD_DEVIATION 9.78 • n=5 Participants	28.85 kilograms STANDARD_DEVIATION 5.89 • n=7 Participants	16.34 kilograms STANDARD_DEVIATION 2.20 • n=5 Participants	35.95 kilograms STANDARD_DEVIATION 19.36 • n=4 Participants
Height	170.6 centimeter STANDARD_DEVIATION 10.7 • n=5 Participants	132.9 centimeter STANDARD_DEVIATION 11.1 • n=7 Participants	101.7 centimeter STANDARD_DEVIATION 8.1 • n=5 Participants	136.9 centimeter STANDARD_DEVIATION 28.3 • n=4 Participants

PRIMARY outcome

Timeframe: up to 15 hours

Population: Pharmacokinetic Set

Mean and Standard Deviation of Serum Concentrations of Tapentadol. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL.

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=19 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). 15 minutes post-dose	23.2 nanogram per milliliter Standard Deviation 34.0	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). 30 minutes post-dose	45.6 nanogram per milliliter Standard Deviation 33.0	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). 1 hour post-dose	49.4 nanogram per milliliter Standard Deviation 21.2	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). 2 hours post-dose	43.1 nanogram per milliliter Standard Deviation 14.2	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). 4 hours post-dose	32.8 nanogram per milliliter Standard Deviation 10.8	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). 6 hours post-dose	22.3 nanogram per milliliter Standard Deviation 11.9	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). 11 hours post-dose	8.14 nanogram per milliliter Standard Deviation 6.35	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). 15 hours post-dose	3.66 nanogram per milliliter Standard Deviation 3.26	—	—

PRIMARY outcome

Timeframe: up to 15 hours

Population: Pharmacokinetic Set

Mean and Standard Deviation of Serum Concentrations of Tapentadol-O-glucuronide. Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as "breakdown products". The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Tapentadol-O-glucuronide concentrations were measured in participants. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 10 ng/mL.

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=18 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). 15 minutes post-dose	404 nanogram per milliliter Standard Deviation 581	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). 30 minutes post-dose	855 nanogram per milliliter Standard Deviation 672	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). 1 hour post-dose	1424 nanogram per milliliter Standard Deviation 542	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). 2 hours post-dose	1202 nanogram per milliliter Standard Deviation 366	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). 4 hours post-dose	824 nanogram per milliliter Standard Deviation 191	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). 6 hours post-dose	497 nanogram per milliliter Standard Deviation 138	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). 11 hours post-dose	150 nanogram per milliliter Standard Deviation 69.0	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years). 15 hours post-dose	66.9 nanogram per milliliter Standard Deviation 35.4	—	—

PRIMARY outcome

Timeframe: up to 15 hours

Mean and Standard Deviation of Serum Concentrations of Tapentadol. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL.

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=22 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Older Children (Age 6 to Less Than 12 Years). 11 to 15 hours post-dose (N=22)	3.71 nanogram per milliliter Standard Deviation 1.96	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Older Children (Age 6 to Less Than 12 Years). 15 minutes to 1 hour post-dose (N=22)	36.5 nanogram per milliliter Standard Deviation 21.8	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Older Children (Age 6 to Less Than 12 Years). 1 to 4 hours post-dose (N=22)	36.5 nanogram per milliliter Standard Deviation 15.7	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Older Children (Age 6 to Less Than 12 Years). 4 to 11 hours post-dose (N=22)	13.5 nanogram per milliliter Standard Deviation 6.52	—	—

PRIMARY outcome

Timeframe: up to 15 hours

Population: Pharmacokinetic Set

Mean and Standard Deviation of Serum Concentrations of Tapentadol-O-glucuronide. Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as "breakdown products". The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Tapentadol-O-glucuronide concentrations were measured in participants. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 10 ng/mL.

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=22 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Older Children (Age 6 to Less Than 12 Years). 11 to 15 hours post-dose	86.3 nanogram per milliliter Standard Deviation 37.8	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Older Children (Age 6 to Less Than 12 Years). 15 minutes to 1 hour post-dose	676 nanogram per milliliter Standard Deviation 343	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Older Children (Age 6 to Less Than 12 Years). 1 to 4 hours post-dose	900 nanogram per milliliter Standard Deviation 330	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Older Children (Age 6 to Less Than 12 Years). 4 to 11 hours post-dose	321 nanogram per milliliter Standard Deviation 123	—	—

PRIMARY outcome

Timeframe: up to 15 hours

Mean and Standard Deviation of Serum Concentrations of Tapentadol. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL.

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=11 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Younger Children (Age 3 to Less Than 6 Years). 15 minutes to 1 hour post-dose (N = 11)	30.1 nanogram per milliliter Standard Deviation 19.2	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Younger Children (Age 3 to Less Than 6 Years). 4 to 11 hours post-dose (N=11)	26.4 nanogram per milliliter Standard Deviation 10.7	—	—

PRIMARY outcome

Timeframe: up to 15 hours

Population: Pharmacokinetic Set

Mean and Standard Deviation of Serum Concentrations of Tapentadol-O-glucuronide. Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as "breakdown products". The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Tapentadol-O-glucuronide concentrations were measured in participants. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 10 ng/mL.

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=11 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Younger Children (Age 3 to Less Than 6 Years). 15 minutes to 1 hour post-dose	494 nanogram per milliliter Standard Deviation 377	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Younger Children (Age 3 to Less Than 6 Years). 4 to 11 hours post-dose	504 nanogram per milliliter Standard Deviation 112	—	—

PRIMARY outcome

Timeframe: up to 15 hours

Population: Pharmacokinetic Set

Mean and Standard Deviation of Serum Concentrations of Tapentadol. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 0.2 ng/mL.

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=4 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Very Young Children (Age 2 to Less Than 3 Years). 1.25 hours post-dose	19.9 nanogram per milliliter Standard Deviation 13.2	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Very Young Children (Age 2 to Less Than 3 Years). 3 hours post-dose	37.7 nanogram per milliliter Standard Deviation 18.2	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Very Young Children (Age 2 to Less Than 3 Years). 5 hours post-dose	23.4 nanogram per milliliter Standard Deviation 6.36	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Very Young Children (Age 2 to Less Than 3 Years). 8 hours post-dose	10.0 nanogram per milliliter Standard Deviation 4.33	—	—

PRIMARY outcome

Timeframe: up to 15 hours

Population: Pharmacokinetic Set

Mean and Standard Deviation of Serum Concentrations of Tapentadol-O-glucuronide. Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as "breakdown products". The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Tapentadol-O-glucuronide concentrations were measured in participants. Serum was analyzed by means of liquid chromatography coupled to tandem mass spectrometry with a lower limit of quantification (LLOQ) at 10 ng/mL.

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=4 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Very Young Children (Age 2 to Less Than 3 Years). 1.25 hours after administration	497 nanogram per milliliter Standard Deviation 513	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Very Young Children (Age 2 to Less Than 3 Years). 3 hours after administration	938 nanogram per milliliter Standard Deviation 407	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Very Young Children (Age 2 to Less Than 3 Years). 5 hours after administration	624 nanogram per milliliter Standard Deviation 235	—	—
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Very Young Children (Age 2 to Less Than 3 Years). 8 hours after administration	253 nanogram per milliliter Standard Deviation 103	—	—

PRIMARY outcome

Timeframe: up to 15 hours

Population: The protocol planned that this analysis would only be performed for the adolescent participants.

Serum samples for pharmacokinetic analysis were obtained using frequent sampling techniques in participants 12 years to less than 18 years of age. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours. The Area Under the Curve (AUC) from dose to 15 hours (AUC 0-15) is a summary measure of data from each pharmacokinetic blood sample taken over the 15 hour time period. The area is that below the line fitted to the data points.

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=18 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Non-Compartmental Pharmacokinetic (PK) Parameter of Tapentadol Area Under the Concentration-Time Curve (AUC 0-15) After a Single Dose of Tapentadol in Adolescent Participants (Age 12 to Less Than 18 Years).	302 ng*hr/mL Interval 218.0 to 636.0	—	—

PRIMARY outcome

Timeframe: up to 15 hours

Population: The protocol planned that this analysis would only be performed for the adolescent participants.

Serum samples for pharmacokinetic analysis were obtained using frequent sampling techniques in participants 12 years to less than 18 years of age. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours. The concentration of tapentadol (active drug) is assessed during absorption and distribution. The maximum concentration is derived from the Area Under the Curve, from dose to 15 hours (AUC 0-15). It is the highest amount of active drug observed in the blood sample

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=18 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Non-Compartmental Pharmacokinetic (PK) Parameter: Cmax (Maximum Concentration) of Tapentadol After a Single Dose of Tapentadol in Adolescents (Age 12 to Less Than 18 Years).	67.5 nanograms/millilitre Standard Error 26.3	—	—

PRIMARY outcome

Timeframe: up to 15 hours

Population: The protocol planned that this analysis would only be performed for the adolescent participants.

Serum samples for pharmacokinetic analysis were obtained using frequent sampling techniques in participants 12 years to less than 18 years of age. The time to maximum concentration is derived from the area under the curve from dose to 15 hours (AUC 0-15). The Tmax is the time after dosing at which the maximum concentration of the tapentadol (active drug) occurs. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours.

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=18 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Non-Compartmental Pharmacokinetic (PK) Parameter: Time to Maximum Concentration (Tmax) of Tapentadol After a Single Dose of Tapentadol in Adolescents (Age 12 to Less Than 18 Years).	1.4 hours Standard Deviation 1.10	—	—

PRIMARY outcome

Timeframe: up to 15 hours

Population: The protocol planned that this analysis would only be performed for the adolescent participants.

Serum samples for pharmacokinetic analysis were obtained using frequent sampling techniques in participants 12 years to less than 18 years of age. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours. The concentration of tapentadol (active drug) is assessed during absorption and distribution. The maximum concentration is derived from the Area Under the Curve, from dose to 15 hours (AUC 0-15). It is the highest amount of active drug observed in the blood sample.

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=18 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Non-Compartmental Pharmacokinetic (PK) Parameter of Tapentadol-O-glucuronide Area Under the Concentration-Time Curve (AUC 0-15) After a Single Dose of Tapentadol in Adolescents (Age 12 to Less Than 18 Years).	7082 ng*hr/mL Interval 4946.0 to 9689.0	—	—

PRIMARY outcome

Timeframe: up to 15 hours

Population: The protocol planned that this analysis would only be performed for the adolescent participants.

Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as "breakdown products". The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours. The concentration of tapentadol-O-glucuronide (metabolite) is assessed to study absorption and distribution. The maximum concentration is derived from the Area Under the Curve, from dose to 15 hours (AUC 0-15). It is the highest amount of metabolite observed in the blood sample.

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=18 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Non-Compartmental Pharmacokinetic (PK) Parameter: Cmax (Maximum Concentration) of Tapentadol-O-glucuronide After a Single Dose of Tapentadol in Adolescents (Age 12 to Less Than 18 Years).	1487 nanogramsg/millilitre Standard Error 495	—	—

PRIMARY outcome

Timeframe: up to 15 hours

Population: The protocol planned that this analysis would only be performed for the adolescent participants.

Tapentadol-O-glucuronide is the metabolite of tapentadol. Metabolites are sometimes referred to as "breakdown products". The body alters the administered medication to a metabolite so that it can be more easily or quickly removed from the body. Serum samples for pharmacokinetic analysis were obtained using frequent sampling techniques in participants 12 years to less than 18 years of age. The time to maximum concentration is derived from the area under the curve from dose to 15 hours (AUC 0-15). The Tmax is the time after dosing at which the maximum concentration of the tapentadol-O-glucuronide (metabolite) occurs. Serum samples (frequent sampling) were drawn at 0.25, 0.5, 1, 2, 4, 6, 11, and 15 hours.

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=18 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Non-Compartmental Pharmacokinetic (PK) Parameter: Time to Maximum Concentration (Tmax) of Tapentadol-O-glucuronide After a Single Dose of Tapentadol in Adolescents (Age 12 to Less Than 18).	1.70 hours Standard Deviation 1.19	—	—

SECONDARY outcome

Timeframe: Baseline; 15 hours

Population: Protocol pre-specified reporting groups.

At predefined times after investigational medicinal product administration, participants were asked to rate their pain on a 100 mm line (visual analog scale - VAS) by marking a point on the line in response to: "My pain at this time is". The mark was scored between "no pain" and " pain as bad as it could be". The distance was then measured by a clinician and reported. A value of 0 indicates "no pain". A value of 100 indicates "pain as bad as it could be".

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=21 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years). Pre-dose	71.5 units on a scale Standard Deviation 13.3	—	—
Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years). 15 minutes post-dose	63.6 units on a scale Standard Deviation 24.4	—	—
Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years). 30 minutes post-dose	53.2 units on a scale Standard Deviation 27.3	—	—
Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years). 1 hour post-dose	46.3 units on a scale Standard Deviation 26.5	—	—
Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years). 2 hours post-dose	34.0 units on a scale Standard Deviation 24.6	—	—
Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years). 4 hours post-dose	43.5 units on a scale Standard Deviation 26.8	—	—
Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years). 6 hours post-dose	34.8 units on a scale Standard Deviation 24.3	—	—
Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years). 11 hours post-dose	32.7 units on a scale Standard Deviation 21.1	—	—
Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years). 15 hours post-dose	33.4 units on a scale Standard Deviation 20.1	—	—

SECONDARY outcome

Timeframe: Baseline; 15 hours post-dose

Population: Protocol pre-specified reporting groups.

Pain intensity assessments were with a 0 (no pain) to 10 (worst pain) scored McGrath color analog scale (CAS) in participants aged 6 years to less than 18 years, i.e. in Adolescents and Older Children. Participants were presented with the CAS and instructed to place the sliding bar on the color that best represented their pain intensity level at the time of assessment. The CAS is a pocket size tool used to measure the self-reported pain intensity of the older participants. The CAS consists of a 145 mm long triangular shaped strip of plastic, varying in width and hue from 1 mm wide and light pink hue at the bottom (and text no pain), to 3 mm wide and deep red hue at the top (most pain). This instrument includes 2 sides. One side shows the color pain intensity scale as described and the other shows a graduated scale, which provides a specific numeric value for the participant-reported level of pain.

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=21 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children n=28 Participants Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). 30 minutes after dosing	5.262 units on a scale Standard Deviation 2.311	2.571 units on a scale Standard Deviation 1.824	—
Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). 1 hour post-dose	4.393 units on a scale Standard Deviation 2.299	2.407 units on a scale Standard Deviation 1.723	—
Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). 15 hours post-dose	3.288 units on a scale Standard Deviation 1.578	3.568 units on a scale Standard Deviation 2.549	—
Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). Pre-dose	6.643 units on a scale Standard Deviation 1.461	4.670 units on a scale Standard Deviation 1.602	—
Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). 15 minutes post-dose	6.131 units on a scale Standard Deviation 2.180	3.071 units on a scale Standard Deviation 1.718	—
Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). 2 hours post-dose	3.475 units on a scale Standard Deviation 2.173	2.292 units on a scale Standard Deviation 1.793	—
Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). 4 hours post-dose	4.200 units on a scale Standard Deviation 2.113	2.341 units on a scale Standard Deviation 1.899	—
Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). 6 hours post-dose	3.438 units on a scale Standard Deviation 1.960	2.636 units on a scale Standard Deviation 2.152	—
Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years). 11 hours post-dose	3.350 units on a scale Standard Deviation 1.836	3.352 units on a scale Standard Deviation 1.851	—

SECONDARY outcome

Timeframe: Baseline; 15 hours post-dose

Population: The protocol pre-specified that the Faces Pain Scale (Revised) would not be administered in the very young participants (aged 2 to less than 3 years).

This assessment tool was used in 3 to less than 12 year old participants, i.e. Older Children and Young Children. The Faces Pain Scale (Revised) \[FPS-R\] score as allocated to a selected face by the participant. There are 6 faces and the participant is asked to indicate on a face to express how much it hurts. The numeric value 0 (no pain) to 10 (very much pain) is read off the reverse side of the scale by the clinician.

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=28 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children n=12 Participants Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. 30 minutes post-dose	2.9 units on a scale Standard Deviation 1.8	2.8 units on a scale Standard Deviation 3.2	—
Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. 1 hour post-dose	2.4 units on a scale Standard Deviation 1.6	1.8 units on a scale Standard Deviation 3.3	—
Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. Pre-dose	4.8 units on a scale Standard Deviation 1.6	6.8 units on a scale Standard Deviation 3.2	—
Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. 15 minutes post-dose	3.5 units on a scale Standard Deviation 1.8	4.5 units on a scale Standard Deviation 4.0	—
Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. 2 hours post-dose	2.6 units on a scale Standard Deviation 1.7	1.2 units on a scale Standard Deviation 2.9	—
Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. 4 hours post-dose	2.5 units on a scale Standard Deviation 1.6	3.5 units on a scale Standard Deviation 3.2	—
Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. 6 hours post-dose	2.7 units on a scale Standard Deviation 2.1	1.8 units on a scale Standard Deviation 2.3	—
Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. 11 hours post-dose	2.7 units on a scale Standard Deviation 1.7	2.3 units on a scale Standard Deviation 2.4	—
Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years. 15 hours post-dose	3.5 units on a scale Standard Deviation 2.2	2.8 units on a scale Standard Deviation 2.9	—

SECONDARY outcome

Timeframe: Baseline; 15 hours post-dose

Population: The protocol pre-specified that the young and very young children will be reported as one group.

The Face Legs Activity Cry Consolability (FLACC) Scale was developed by the Department of Anesthesiology, University of Michigan Medical School and Health Systems. The FLACC Scale is a behavioral scale for scoring postoperative pain in children between the ages of two months and seven years or in persons unable to communicate. In this trial the scale was used in the young and very young children, i.e. in participants aged 2 to less than 6 years. This tool includes five categories of pain behaviors, including facial expression, leg movement, activity, cry, and consolability. The clinician observes the participant for 5 minutes or more and scores each category with a 0, 1 or 2. The scores are added together for a total score ranging from 0 (no pain) to 10 (worst pain). The higher the total score the higher the pain.

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=17 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years). Pre-dose	4.2 units on a scale Standard Deviation 2.2	—	—
Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years). 15 minutes post-dose	1.8 units on a scale Standard Deviation 1.6	—	—
Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years). 30 minutes post-dose	1.2 units on a scale Standard Deviation 1.6	—	—
Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years). 1 hour post-dose	1.1 units on a scale Standard Deviation 1.4	—	—
Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years). 2 hours post-dose	0.8 units on a scale Standard Deviation 1.1	—	—
Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years). 4 hours post-dose	1.5 units on a scale Standard Deviation 1.7	—	—
Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years). 6 hours post-dose	0.8 units on a scale Standard Deviation 1.6	—	—
Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years). 11 hours post-dose	0.9 units on a scale Standard Deviation 2.1	—	—
Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years). 15 hours post-dose	0.8 units on a scale Standard Deviation 1.2	—	—

SECONDARY outcome

Timeframe: Baseline; 4 hours post-dose

Population: Protocol pre-specified reporting groups.

Different pain intensity assessment tools were used in the different age groups. Therefore the sum of pain intensities were calculated and are reported for each age group based on the tool used. Adolescents - Age 12 to Less Than 18 Years. Older Children - Age 6 to Less Than 12 Years. Young Children - Age 3 to Less Than 6 Years. Very Young Children - Age 2 to Less Than 3 Years. * CAS (McGrath color analog scale) \[Theoretical Range: -40 to + 40\], * VAS (100 mm Visual Analog Scale) \[Theoretical Range: -400 to + 400\], * FPS-R (6-point Faces Pain Scale - Revised) \[Theoretical Range: -40 to + 40\], * FLACC (Face, Legs, Activity, Cry, and Consolability score) \[Theoretical Range: -40 to + 40\]. A mean score of zero indicates that there was no pain intensity change over the 4 hours. The positive values indicate that in the group as a whole the sum of all pain intensity values over the first 4 hours lead to a reduction in pain in the time period.

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=65 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Sum of Pain Intensity Differences Over the 4 Hours After Dosing Derived From the Different Pain Scales and for All Age Groups Older Children SPID for FPS-R	8.724 units on a scale Standard Deviation 6.868	—	—
Sum of Pain Intensity Differences Over the 4 Hours After Dosing Derived From the Different Pain Scales and for All Age Groups Adolescents SPID for VAS	106.282 units on a scale Standard Deviation 75.350	—	—
Sum of Pain Intensity Differences Over the 4 Hours After Dosing Derived From the Different Pain Scales and for All Age Groups Adolescents SPID for CAS	8.925 units on a scale Standard Deviation 6.347	—	—
Sum of Pain Intensity Differences Over the 4 Hours After Dosing Derived From the Different Pain Scales and for All Age Groups Older Children SPID for CAS	9.698 units on a scale Standard Deviation 7.610	—	—
Sum of Pain Intensity Differences Over the 4 Hours After Dosing Derived From the Different Pain Scales and for All Age Groups Young Children SPID for FPS-R	17.646 units on a scale Standard Deviation 14.674	—	—
Sum of Pain Intensity Differences Over the 4 Hours After Dosing Derived From the Different Pain Scales and for All Age Groups Young Children SPID for FLACC	11.614 units on a scale Standard Deviation 8.334	—	—
Sum of Pain Intensity Differences Over the 4 Hours After Dosing Derived From the Different Pain Scales and for All Age Groups Very Young Children SPID for FLACC	12.483 units on a scale Standard Deviation 8.955	—	—

SECONDARY outcome

Timeframe: Enrollment Visit; 15 hours post-dose

Population: The protocol pre-specified that the young and very young children will be reported as one group. (Adolescents Group at and after 2 hours: N=20; Older Children Group at 30 minutes and 1 hour N=27, at 2 hours N=24, and at and after 4 hours N=22; Young and Very Young Children Group at and after 4 hours: N=16).

Respiratory rate assessments were performed at pre-defined times during the 15 hour period following investigational medicinal product intake. Pre-surgery data for these participants is also given from the enrollment Visit (Visit 1).

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=21 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children n=28 Participants Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children n=17 Participants Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Respiratory Rate Assessments Visit 1	17.8 breaths per minute Standard Deviation 3.2	18.4 breaths per minute Standard Deviation 3.1	25.1 breaths per minute Standard Deviation 3.4
Respiratory Rate Assessments Pre-dose	16.4 breaths per minute Standard Deviation 2.5	19.2 breaths per minute Standard Deviation 2.5	25.1 breaths per minute Standard Deviation 3.3
Respiratory Rate Assessments 15 minutes post-dose	16.8 breaths per minute Standard Deviation 2.6	19.7 breaths per minute Standard Deviation 2.5	24.0 breaths per minute Standard Deviation 3.1
Respiratory Rate Assessments 30 minutes post-dose	17.5 breaths per minute Standard Deviation 2.5	19.4 breaths per minute Standard Deviation 2.4	22.6 breaths per minute Standard Deviation 4.3
Respiratory Rate Assessments 1 hours post-dose	15.9 breaths per minute Standard Deviation 2.3	19.0 breaths per minute Standard Deviation 2.0	21.8 breaths per minute Standard Deviation 3.5
Respiratory Rate Assessments 2 hours post-dose	17.3 breaths per minute Standard Deviation 2.8	19.3 breaths per minute Standard Deviation 2.5	22.5 breaths per minute Standard Deviation 3.3
Respiratory Rate Assessments 4 hours post-dose	16.4 breaths per minute Standard Deviation 2.1	19.5 breaths per minute Standard Deviation 2.8	22.5 breaths per minute Standard Deviation 2.1
Respiratory Rate Assessments 6 hours post-dose	16.9 breaths per minute Standard Deviation 2.9	19.0 breaths per minute Standard Deviation 3.8	22.1 breaths per minute Standard Deviation 3.5
Respiratory Rate Assessments 11 hours post-dose	17.4 breaths per minute Standard Deviation 3.6	18.4 breaths per minute Standard Deviation 2.9	22.4 breaths per minute Standard Deviation 3.4
Respiratory Rate Assessments 15 hours post-dose	16.1 breaths per minute Standard Deviation 2.5	17.3 breaths per minute Standard Deviation 3.0	21.1 breaths per minute Standard Deviation 3.9

SECONDARY outcome

Timeframe: Enrollment Visit; 15 hours post-dose

Population: The protocol pre-specified that the young and very young children will be reported as one group. (Adolescents Group at and after 2 hours: N=20; Older Children Group at 30 minutes and 1 hour N=27, at 2 hours N=24, at and after 4 hours N=22; Young and Very Young Children Group at and after 4 hours: N=16).

Oxygen saturation assessments were performed at pre-defined times during the 15 hour period following investigational medicinal product intake. Oxygen saturation was assessed using pulse oximetry. The uppermost value is 100%. Pre-surgery data for these participants is also given from the enrollment Visit (Visit 1).

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=21 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children n=28 Participants Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children n=17 Participants Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Oxygen Saturation Assessments Pre-dose	97.7 percentage of oxygen saturation Standard Deviation 1.4	96.7 percentage of oxygen saturation Standard Deviation 1.4	96.8 percentage of oxygen saturation Standard Deviation 1.0
Oxygen Saturation Assessments 15 minutes post-dose	97.3 percentage of oxygen saturation Standard Deviation 1.2	96.8 percentage of oxygen saturation Standard Deviation 1.3	96.5 percentage of oxygen saturation Standard Deviation 1.9
Oxygen Saturation Assessments Visit 1	97.8 percentage of oxygen saturation Standard Deviation 1.1	97.4 percentage of oxygen saturation Standard Deviation 1.7	97.4 percentage of oxygen saturation Standard Deviation 1.4
Oxygen Saturation Assessments 30 minutes post-dose	97.0 percentage of oxygen saturation Standard Deviation 1.4	96.4 percentage of oxygen saturation Standard Deviation 1.3	96.8 percentage of oxygen saturation Standard Deviation 1.6
Oxygen Saturation Assessments 1 hour post-dose	97.3 percentage of oxygen saturation Standard Deviation 1.2	96.0 percentage of oxygen saturation Standard Deviation 1.6	96.2 percentage of oxygen saturation Standard Deviation 2.0
Oxygen Saturation Assessments 2 hours post-dose	97.1 percentage of oxygen saturation Standard Deviation 1.3	95.8 percentage of oxygen saturation Standard Deviation 1.4	95.8 percentage of oxygen saturation Standard Deviation 1.7
Oxygen Saturation Assessments 4 hours post-dose	96.9 percentage of oxygen saturation Standard Deviation 1.4	96.5 percentage of oxygen saturation Standard Deviation 1.2	96.5 percentage of oxygen saturation Standard Deviation 1.5
Oxygen Saturation Assessments 6 hours post-dose	97.1 percentage of oxygen saturation Standard Deviation 1.5	96.7 percentage of oxygen saturation Standard Deviation 1.3	96.7 percentage of oxygen saturation Standard Deviation 1.7
Oxygen Saturation Assessments 11 hours post-dose	96.8 percentage of oxygen saturation Standard Deviation 1.4	96.8 percentage of oxygen saturation Standard Deviation 1.4	96.4 percentage of oxygen saturation Standard Deviation 1.5
Oxygen Saturation Assessments 15 hours post-dose	96.7 percentage of oxygen saturation Standard Deviation 1.0	96.5 percentage of oxygen saturation Standard Deviation 1.4	97.1 percentage of oxygen saturation Standard Deviation 1.5

SECONDARY outcome

Timeframe: Enrollment Visit; 15 hours post-dose

Population: The protocol pre-specified that the young and very young children will be reported as one group. (Adolescents Group at and after 2 hours: N=20; Older Children Group at 30 minutes and 1 hour N=27, at 2 hours N=24, at and after 4 hours N=22; Young and Very Young Children Group at and after 4 hours: N=16).

Systolic and Diastolic blood pressure assessments were performed at pre-defined times during the 15 hour period following investigational medicinal product intake. Pre-surgery data for these participants is also given from the enrollment Visit (Visit 1).

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=21 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children n=28 Participants Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children n=17 Participants Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Systolic and Diastolic Blood Pressure Assessments 11 hours post-dose Diastolic blood pressure	65.4 mmHg Standard Deviation 8.4	54.6 mmHg Standard Deviation 8.5	57.3 mmHg Standard Deviation 11.2
Systolic and Diastolic Blood Pressure Assessments Visit 1 Enrollment Systolic blood pressure	110.2 mmHg Standard Deviation 9.0	103.8 mmHg Standard Deviation 9.6	98.7 mmHg Standard Deviation 7.0
Systolic and Diastolic Blood Pressure Assessments Pre-dose Systolic Blood Pressure	122.9 mmHg Standard Deviation 13.9	107.1 mmHg Standard Deviation 9.1	105.1 mmHg Standard Deviation 15.6
Systolic and Diastolic Blood Pressure Assessments 15 minutes post-dose Systolic Blood Pressure	126.9 mmHg Standard Deviation 17.7	104.1 mmHg Standard Deviation 8.3	101.8 mmHg Standard Deviation 7.5
Systolic and Diastolic Blood Pressure Assessments 30 minutes post-dose Systolic Blood Pressure	126.8 mmHg Standard Deviation 17.9	104.1 mmHg Standard Deviation 7.2	100.1 mmHg Standard Deviation 6.2
Systolic and Diastolic Blood Pressure Assessments 1 hour post-dose Systolic Blood Pressure	127.0 mmHg Standard Deviation 17.7	104.0 mmHg Standard Deviation 9.6	97.6 mmHg Standard Deviation 7.6
Systolic and Diastolic Blood Pressure Assessments 2 hours post-dose Systolic Blood Pressure	124.9 mmHg Standard Deviation 16.7	103.9 mmHg Standard Deviation 8.2	98.4 mmHg Standard Deviation 6.6
Systolic and Diastolic Blood Pressure Assessments 4 hours post-dose Systolic Blood Pressure	122.8 mmHg Standard Deviation 13.9	104.8 mmHg Standard Deviation 10.5	100.1 mmHg Standard Deviation 7.4
Systolic and Diastolic Blood Pressure Assessments 6 hours post-dose Systolic Blood Pressure	116.8 mmHg Standard Deviation 14.1	106.7 mmHg Standard Deviation 7.9	102.0 mmHg Standard Deviation 8.5
Systolic and Diastolic Blood Pressure Assessments 11 hours post-dose Systolic Blood Pressure	115.1 mmHg Standard Deviation 11.2	102.0 mmHg Standard Deviation 9.1	99.4 mmHg Standard Deviation 14.2
Systolic and Diastolic Blood Pressure Assessments 15 hours post-dose Systolic Blood Pressure	113.8 mmHg Standard Deviation 14.2	100.3 mmHg Standard Deviation 8.7	93.3 mmHg Standard Deviation 9.9
Systolic and Diastolic Blood Pressure Assessments Visit 1 Enrollment Diastolic blood pressure	66.5 mmHg Standard Deviation 9.0	66.3 mmHg Standard Deviation 8.3	62.8 mmHg Standard Deviation 5.3
Systolic and Diastolic Blood Pressure Assessments Pre-dose Diastolic blood pressure	74.8 mmHg Standard Deviation 11.8	64.2 mmHg Standard Deviation 9.4	65.6 mmHg Standard Deviation 11.2
Systolic and Diastolic Blood Pressure Assessments 15 minutes post-dose Diastolic blood pressure	78.9 mmHg Standard Deviation 15.7	62.4 mmHg Standard Deviation 7.8	62.4 mmHg Standard Deviation 7.7
Systolic and Diastolic Blood Pressure Assessments 30 minutes post-dose Diastolic blood pressure	76.1 mmHg Standard Deviation 12.0	61.3 mmHg Standard Deviation 5.7	60.2 mmHg Standard Deviation 6.1
Systolic and Diastolic Blood Pressure Assessments 1 hour post-dose Diastolic blood pressure	77.6 mmHg Standard Deviation 13.0	61.1 mmHg Standard Deviation 7.1	59.6 mmHg Standard Deviation 6.9
Systolic and Diastolic Blood Pressure Assessments 2 hours post-dose Diastolic blood pressure	74.7 mmHg Standard Deviation 13.4	59.7 mmHg Standard Deviation 7.0	59.7 mmHg Standard Deviation 7.4
Systolic and Diastolic Blood Pressure Assessments 4 hours post-dose Diastolic blood pressure	73.2 mmHg Standard Deviation 12.1	60.0 mmHg Standard Deviation 7.1	58.7 mmHg Standard Deviation 5.9
Systolic and Diastolic Blood Pressure Assessments 6 hours post-dose Diastolic blood pressure	66.0 mmHg Standard Deviation 10.3	59.0 mmHg Standard Deviation 8.3	58.8 mmHg Standard Deviation 7.3
Systolic and Diastolic Blood Pressure Assessments 15 hours post-dose Diastolic blood pressure	67.1 mmHg Standard Deviation 10.8	56.8 mmHg Standard Deviation 8.5	57.0 mmHg Standard Deviation 8.7

SECONDARY outcome

Timeframe: Enrollment (pre-surgery); Discharge Visit

Population: The protocol pre-specified that the young and very young children will be reported as one group. (For older children N=27 at Visit 1)

12-lead electrocardiograms (ECG) were part of the planned safety assessments. 12-lead Electrocardiograms were performed prior at the enrollment visit after informed consent and at the discharge visit. The discharge visit was as per standard of care. The changes in ECG parameters are reported. Negative mean values indicate that the millisecond intervals decreased from the enrollment to the discharge visit. Positive mean values indicate that the millisecond intervals increased from the enrollment to the discharge visit. The Letters P,Q,R,S and T refer to specific medically defined points on an ECG tracing and correspond to specific heart activities.

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=21 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children n=27 Participants Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children n=17 Participants Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Change From Enrollment in 12-lead Electrocardiogram Parameters QTcF change	-3.6 milliseconds Standard Deviation 16.4	15.7 milliseconds Standard Deviation 21.7	5.6 milliseconds Standard Deviation 20.7
Change From Enrollment in 12-lead Electrocardiogram Parameters QT Duration change	-8.0 milliseconds Standard Deviation 33.1	8.5 milliseconds Standard Deviation 32.0	-4.1 milliseconds Standard Deviation 29.6
Change From Enrollment in 12-lead Electrocardiogram Parameters QRS Duration change	0.5 milliseconds Standard Deviation 4.5	-0.2 milliseconds Standard Deviation 4.7	0.5 milliseconds Standard Deviation 5.8
Change From Enrollment in 12-lead Electrocardiogram Parameters PR Duration change	-3.5 milliseconds Standard Deviation 11.7	-1.8 milliseconds Standard Deviation 11.3	-2.4 milliseconds Standard Deviation 12.6
Change From Enrollment in 12-lead Electrocardiogram Parameters RR Duration change	-32.2 milliseconds Standard Deviation 193.8	-35.2 milliseconds Standard Deviation 156.5	-48.1 milliseconds Standard Deviation 102.8

SECONDARY outcome

Timeframe: Enrollment; Discharge Visit

Population: The protocol pre-specified that the young and very young children will be reported as one group. (For older children: N=27 at Visit 1)

12-lead Electrocardiograms (ECG) were part of the planned safety assessments. 12-lead Electrocardiograms were performed prior at the enrollment visit after informed consent and at the discharge visit. The discharge visit was as per standard of care. The changes in heart rate (beats per minute) parameters are reported per treatment group between the visits. A positive value indicates that the heart rate was higher at discharge than at enrollment.

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=21 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children n=28 Participants Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children n=17 Participants Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Change From Enrollment in 12-lead Electrocardiogram Heart Rate Parameter	2.0 beats per minute Standard Deviation 16.4	4.3 beats per minute Standard Deviation 16.2	10.7 beats per minute Standard Deviation 16.4

SECONDARY outcome

Timeframe: Baseline; 48 hours post dosing

Population: The protocol pre-specified that the young and very young children will be reported as one group.

The intensity of all treatment emergent adverse events (TEAEs) were scored by the investigator. Treatment emergent adverse events were those adverse events documented from the time of investigational medicinal product (IMP), study drug, up to 48 hours post dosing. The clinical "intensity" of an adverse event was classified as: * Mild: Signs and symptoms that can be easily tolerated. Symptoms can be ignored and disappear when the subject is distracted. * Moderate: Symptoms cause discomfort but are tolerable; they cannot be ignored and affect concentration. * Severe: Symptoms which affect usual daily activity. For adverse events where the intensity changes over time, the maximum intensity observed was documented.

Outcome measures

Outcome measures
Measure	Tapentadol Serum Concentrations: Adolescents n=21 Participants Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	McGrath Color Analog Scale: Older Children n=28 Participants Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Respiratory Rates: Young and Very Young Children n=17 Participants Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Treatment Emergent Adverse Events by Intensity Total number of TEAEs	22 number of events	33 number of events	11 number of events
Treatment Emergent Adverse Events by Intensity Total number of mild TEAEs	10 number of events	16 number of events	10 number of events
Treatment Emergent Adverse Events by Intensity Total number of moderate TEAEs	12 number of events	17 number of events	1 number of events

SECONDARY outcome

Timeframe: Baseline; 15 hours post dosing

Population: The protocol pre-specified that the young and very young children will be reported as one group.

Number of participants with intakes of supplemental analgesic medication between investigational medicinal product (IMP) intake and Site Discharge grouped according to preparation taken (non-opioid/opioid).