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

• ClinicalTrials.gov Identifier: NCT01729728
• Recruitment Status: Completed
• First Posted: November 20, 2012
• Results First Posted: November 27, 2014
• Last Update Posted: November 4, 2019
• Sponsor: Grünenthal GmbH
• Collaborator: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Grünenthal GmbH

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Postoperative Pain; Acute Pain
• Intervention: Drug: Tapentadol
• Enrollment: 86

Participant Flow

Recruitment Details	The first participant was enrolled on the 15 Nov 2012 and the last participant completed the trial on the 24 Feb 2014.
Pre-assignment Details	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.

Arm/Group Title	Adolescents	Older Children	Young and Very Young Children
Arm/Group Description	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight)	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight)	Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight)
Period Title: Overall Study
Started	21	28	17
Completed	20	22	16
Not Completed	1	6	1
Reason Not Completed
Adverse Event	0	6	0
Protocol Violation	1	0	1

Baseline Characteristics

Arm/Group Title		Adolescents	Older Children	Young and Very Young Children	Total
Arm/Group Description		Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 of all reporting groups
Overall Number of Baseline Participants		21	28	17	66
Baseline Analysis Population Description		Number of participants that were dosed.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	21 participants	28 participants	17 participants	66 participants
		15.5 (1.6)	8.3 (1.6)	3.4 (1.1)	9.3 (4.9)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	21 participants	28 participants	17 participants	66 participants
	Female	9 42.9%	17 60.7%	8 47.1%	34 51.5%
	Male	12 57.1%	11 39.3%	9 52.9%	32 48.5%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	21 participants	28 participants	17 participants	66 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	1 3.6%	0 0.0%	1 1.5%
	White	21 100.0%	27 96.4%	15 88.2%	63 95.5%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	2 11.8%	2 3.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	21 participants	28 participants	17 participants	66 participants
		21	28	17	66
Weight; Mean (Standard Deviation); Unit of measure: Kilograms
	Number Analyzed	21 participants	28 participants	17 participants	66 participants
		61.30 (9.78)	28.85 (5.89)	16.34 (2.20)	35.95 (19.36)
Height; Mean (Standard Deviation); Unit of measure: Centimeter
	Number Analyzed	21 participants	28 participants	17 participants	66 participants
		170.6 (10.7)	132.9 (11.1)	101.7 (8.1)	136.9 (28.3)

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetic Profile of Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Adolescents (Age 12 to Less Than 18 Years).
Description	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.
Time Frame	up to 15 hours

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set

Arm/Group Title		Tapentadol Serum Concentrations: Adolescents
Arm/Group Description:		Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.
Overall Number of Participants Analyzed		19
Mean (Standard Deviation); Unit of Measure: nanogram per milliliter
15 minutes post-dose	Number Analyzed	19 participants
		23.2 (34.0)
30 minutes post-dose	Number Analyzed	18 participants
		45.6 (33.0)
1 hour post-dose	Number Analyzed	18 participants
		49.4 (21.2)
2 hours post-dose	Number Analyzed	18 participants
		43.1 (14.2)
4 hours post-dose	Number Analyzed	17 participants
		32.8 (10.8)
6 hours post-dose	Number Analyzed	18 participants
		22.3 (11.9)
11 hours post-dose	Number Analyzed	18 participants
		8.14 (6.35)
15 hours post-dose	Number Analyzed	17 participants
		3.66 (3.26)

2. Primary Outcome

Title	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).
Description	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.
Time Frame	up to 15 hours

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set

Arm/Group Title		Tapentadol-O-glucuronide Serum Concentrations: Adolescents
Arm/Group Description:		Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.
Overall Number of Participants Analyzed		18
Mean (Standard Deviation); Unit of Measure: nanogram per milliliter
15 minutes post-dose	Number Analyzed	18 participants
		404 (581)
30 minutes post-dose	Number Analyzed	17 participants
		855 (672)
1 hour post-dose	Number Analyzed	17 participants
		1424 (542)
2 hours post-dose	Number Analyzed	18 participants
		1202 (366)
4 hours post-dose	Number Analyzed	17 participants
		824 (191)
6 hours post-dose	Number Analyzed	18 participants
		497 (138)
11 hours post-dose	Number Analyzed	18 participants
		150 (69.0)
15 hours post-dose	Number Analyzed	17 participants
		66.9 (35.4)

3. Primary Outcome

Title	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).
Description	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.
Time Frame	up to 15 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tapentadol Serum Concentrations: Older Children
Arm/Group Description:	Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 6 years and less than 12 years of age.
Overall Number of Participants Analyzed	22
Mean (Standard Deviation); Unit of Measure: nanogram per milliliter
15 minutes to 1 hour post-dose (N=22)	36.5 (21.8)
1 to 4 hours post-dose (N=22)	36.5 (15.7)
4 to 11 hours post-dose (N=22)	13.5 (6.52)
11 to 15 hours post-dose (N=22)	3.71 (1.96)

4. Primary Outcome

Title	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).
Description	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.
Time Frame	up to 15 hours

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set

Arm/Group Title		Tapentadol-O-glucuronide Serum Concentrations: Older Children
Arm/Group Description:		Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 6 years and less than 12 years of age.
Overall Number of Participants Analyzed		22
Mean (Standard Deviation); Unit of Measure: nanogram per milliliter
15 minutes to 1 hour post-dose	Number Analyzed	20 participants
		676 (343)
1 to 4 hours post-dose	Number Analyzed	22 participants
		900 (330)
4 to 11 hours post-dose	Number Analyzed	22 participants
		321 (123)
11 to 15 hours post-dose	Number Analyzed	22 participants
		86.3 (37.8)

5. Primary Outcome

Title	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).
Description	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.
Time Frame	up to 15 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tapentadol Serum Concentrations: Younger Children
Arm/Group Description:	Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 3 years and less than 6 years of age.
Overall Number of Participants Analyzed	11
Mean (Standard Deviation); Unit of Measure: nanogram per milliliter
15 minutes to 1 hour post-dose (N = 11)	30.1 (19.2)
4 to 11 hours post-dose (N=11)	26.4 (10.7)

6. Primary Outcome

Title	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).
Description	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.
Time Frame	up to 15 hours

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set

Arm/Group Title		Tapentadol-O-glucuronide Serum Concentrations Younger Children
Arm/Group Description:		Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 3 years and less than 6 years of age.
Overall Number of Participants Analyzed		11
Mean (Standard Deviation); Unit of Measure: nanogram per milliliter
15 minutes to 1 hour post-dose	Number Analyzed	10 participants
		494 (377)
4 to 11 hours post-dose	Number Analyzed	11 participants
		504 (112)

7. Primary Outcome

Title	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).
Description	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.
Time Frame	up to 15 hours

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set

Arm/Group Title		Tapentadol Serum Concentrations: Very Young Children
Arm/Group Description:		Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 2 years and less than 3 years of age.
Overall Number of Participants Analyzed		4
Mean (Standard Deviation); Unit of Measure: nanogram per milliliter
1.25 hours post-dose	Number Analyzed	4 participants
		19.9 (13.2)
3 hours post-dose	Number Analyzed	4 participants
		37.7 (18.2)
5 hours post-dose	Number Analyzed	3 participants
		23.4 (6.36)
8 hours post-dose	Number Analyzed	4 participants
		10.0 (4.33)

8. Primary Outcome

Title	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).
Description	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.
Time Frame	up to 15 hours

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set

Arm/Group Title		Tapentadol-O-glucuronide Concentrations: Very Young Children
Arm/Group Description:		Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 2 years and less than 3 years of age.
Overall Number of Participants Analyzed		4
Mean (Standard Deviation); Unit of Measure: nanogram per milliliter
1.25 hours after administration	Number Analyzed	4 participants
		497 (513)
3 hours after administration	Number Analyzed	4 participants
		938 (407)
5 hours after administration	Number Analyzed	3 participants
		624 (235)
8 hours after administration	Number Analyzed	4 participants
		253 (103)

9. Primary Outcome

Title	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).
Description	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.
Time Frame	up to 15 hours

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol Non-Compartmental PK Parameter: AUC
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Overall Number of Participants Analyzed	18
Mean (Full Range); Unit of Measure: ng*hr/mL
	302; (218 to 636)

10. Primary Outcome

Title	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).
Description	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
Time Frame	up to 15 hours

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol Non-Compartmental PK Parameter: Cmax
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Overall Number of Participants Analyzed	18
Mean (Standard Error); Unit of Measure: nanograms/millilitre
	67.5 (26.3)

11. Primary Outcome

Title	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).
Description	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.
Time Frame	up to 15 hours

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol Non-Compartmental PK Parameter: Tmax
Arm/Group Description:	Tapentadol oral solution single dose (1mg/kg body weight) of participants aged 12 years to less than 18 years old.
Overall Number of Participants Analyzed	18
Mean (Standard Deviation); Unit of Measure: hours
	1.4 (1.10)

12. Primary Outcome

Title	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).
Description	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.
Time Frame	up to 15 hours

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol-O-glucuronide Non-Compartmental PK Parameter: AUC
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Overall Number of Participants Analyzed	18
Mean (Full Range); Unit of Measure: ng*hr/mL
	7082; (4946 to 9689)

13. Primary Outcome

Title	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).
Description	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.
Time Frame	up to 15 hours

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol-O-glucuronide Non-Compartmental PK Parameter: Cmax
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Overall Number of Participants Analyzed	18
Mean (Standard Error); Unit of Measure: nanogramsg/millilitre
	1487 (495)

14. Primary Outcome

Title	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).
Description	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.
Time Frame	up to 15 hours

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tapentadol-O-glucuronide Non-Compartmental PK Parameter: Tmax
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Overall Number of Participants Analyzed	18
Mean (Standard Deviation); Unit of Measure: hours
	1.70 (1.19)

15. Secondary Outcome

Title	Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescents (Age 12 to Less Than 18 Years).
Description	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".
Time Frame	Baseline; 15 hours

Outcome Measure Data

Analysis Population Description

Protocol pre-specified reporting groups.

Arm/Group Title		Visual Analog Scale: Adolescents
Arm/Group Description:		Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Overall Number of Participants Analyzed		21
Mean (Standard Deviation); Unit of Measure: units on a scale
Pre-dose	Number Analyzed	21 participants
		71.5 (13.3)
15 minutes post-dose	Number Analyzed	21 participants
		63.6 (24.4)
30 minutes post-dose	Number Analyzed	21 participants
		53.2 (27.3)
1 hour post-dose	Number Analyzed	21 participants
		46.3 (26.5)
2 hours post-dose	Number Analyzed	20 participants
		34.0 (24.6)
4 hours post-dose	Number Analyzed	20 participants
		43.5 (26.8)
6 hours post-dose	Number Analyzed	20 participants
		34.8 (24.3)
11 hours post-dose	Number Analyzed	20 participants
		32.7 (21.1)
15 hours post-dose	Number Analyzed	20 participants
		33.4 (20.1)

16. Secondary Outcome

Title	Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Age 6 to Less Than 18 Years).
Description	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.
Time Frame	Baseline; 15 hours post-dose

Outcome Measure Data

Analysis Population Description

Protocol pre-specified reporting groups.

Arm/Group Title	McGrath Color Analog Scale: Adolescents	McGrath Color Analog Scale: Older Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Overall Number of Participants Analyzed	21	28
Mean (Standard Deviation); Unit of Measure: units on a scale
Pre-dose	6.643 (1.461)	4.670 (1.602)
15 minutes post-dose	6.131 (2.180)	3.071 (1.718)
30 minutes after dosing	5.262 (2.311)	2.571 (1.824)
1 hour post-dose	4.393 (2.299)	2.407 (1.723)
2 hours post-dose	3.475 (2.173)	2.292 (1.793)
4 hours post-dose	4.200 (2.113)	2.341 (1.899)
6 hours post-dose	3.438 (1.960)	2.636 (2.152)
11 hours post-dose	3.350 (1.836)	3.352 (1.851)
15 hours post-dose	3.288 (1.578)	3.568 (2.549)

17. Secondary Outcome

Title	Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years.
Description	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.
Time Frame	Baseline; 15 hours post-dose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Faces Pain Scale: Older Children	Faces Pain Scale: Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight)	Single Dose of Tapentadol Oral Solution in Children Age 3 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight). The children aged 2 were assessed using the FLACC (Face, Legs, Activity, Cry, Consolability) Scale and not the 6-point Faces Pain Scale - Revised.
Overall Number of Participants Analyzed	28	12
Mean (Standard Deviation); Unit of Measure: units on a scale
Pre-dose	4.8 (1.6)	6.8 (3.2)
15 minutes post-dose	3.5 (1.8)	4.5 (4.0)
30 minutes post-dose	2.9 (1.8)	2.8 (3.2)
1 hour post-dose	2.4 (1.6)	1.8 (3.3)
2 hours post-dose	2.6 (1.7)	1.2 (2.9)
4 hours post-dose	2.5 (1.6)	3.5 (3.2)
6 hours post-dose	2.7 (2.1)	1.8 (2.3)
11 hours post-dose	2.7 (1.7)	2.3 (2.4)
15 hours post-dose	3.5 (2.2)	2.8 (2.9)

18. Secondary Outcome

Title	Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years).
Description	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.
Time Frame	Baseline; 15 hours post-dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Face, Legs, Activity, Cry, Consolability Scale
Arm/Group Description:	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 Number of Participants Analyzed	17
Mean (Standard Deviation); Unit of Measure: units on a scale
Pre-dose	4.2 (2.2)
15 minutes post-dose	1.8 (1.6)
30 minutes post-dose	1.2 (1.6)
1 hour post-dose	1.1 (1.4)
2 hours post-dose	0.8 (1.1)
4 hours post-dose	1.5 (1.7)
6 hours post-dose	0.8 (1.6)
11 hours post-dose	0.9 (2.1)
15 hours post-dose	0.8 (1.2)

19. Secondary Outcome

Title	Sum of Pain Intensity Differences Over the 4 Hours After Dosing Derived From the Different Pain Scales and for All Age Groups
Description	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.
Time Frame	Baseline; 4 hours post-dose

Outcome Measure Data

Analysis Population Description

Protocol pre-specified reporting groups.

Arm/Group Title		Sum of Pain Intensity Differences
Arm/Group Description:		The sum of pain intensity difference over 4 hours (SPID4) were calculated as the weighted sum of the scheduled pain intensity difference collected up to 4 hours after tapentadol oral solution administration. The time elapsed (in hours) since the previous measurement is multiplied with the pain intensity difference (PID) at the respective time, and defines the weight in the calculation of the weighted sum of pain intensity differences.
Overall Number of Participants Analyzed		65
Mean (Standard Deviation); Unit of Measure: units on a scale
Adolescents SPID for VAS	Number Analyzed	20 participants
		106.282 (75.350)
Adolescents SPID for CAS	Number Analyzed	20 participants
		8.925 (6.347)
Older Children SPID for CAS	Number Analyzed	22 participants
		9.698 (7.610)
Older Children SPID for FPS-R	Number Analyzed	22 participants
		8.724 (6.868)
Young Children SPID for FPS-R	Number Analyzed	11 participants
		17.646 (14.674)
Young Children SPID for FLACC	Number Analyzed	12 participants
		11.614 (8.334)
Very Young Children SPID for FLACC	Number Analyzed	4 participants
		12.483 (8.955)

20. Secondary Outcome

Title	Respiratory Rate Assessments
Description	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).
Time Frame	Enrollment Visit; 15 hours post-dose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Respiratory Rates: Adolescents	Respiratory Rates: Older Children	Respiratory Rates: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: breaths per minute
Visit 1	17.8 (3.2)	18.4 (3.1)	25.1 (3.4)
Pre-dose	16.4 (2.5)	19.2 (2.5)	25.1 (3.3)
15 minutes post-dose	16.8 (2.6)	19.7 (2.5)	24.0 (3.1)
30 minutes post-dose	17.5 (2.5)	19.4 (2.4)	22.6 (4.3)
1 hours post-dose	15.9 (2.3)	19.0 (2.0)	21.8 (3.5)
2 hours post-dose	17.3 (2.8)	19.3 (2.5)	22.5 (3.3)
4 hours post-dose	16.4 (2.1)	19.5 (2.8)	22.5 (2.1)
6 hours post-dose	16.9 (2.9)	19.0 (3.8)	22.1 (3.5)
11 hours post-dose	17.4 (3.6)	18.4 (2.9)	22.4 (3.4)
15 hours post-dose	16.1 (2.5)	17.3 (3.0)	21.1 (3.9)

21. Secondary Outcome

Title	Oxygen Saturation Assessments
Description	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).
Time Frame	Enrollment Visit; 15 hours post-dose

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Oxygen Saturation: Adolescents	Oxygen Saturation: Older Children	Oxygen Saturation: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: percentage of oxygen saturation
Visit 1	97.8 (1.1)	97.4 (1.7)	97.4 (1.4)
Pre-dose	97.7 (1.4)	96.7 (1.4)	96.8 (1.0)
15 minutes post-dose	97.3 (1.2)	96.8 (1.3)	96.5 (1.9)
30 minutes post-dose	97.0 (1.4)	96.4 (1.3)	96.8 (1.6)
1 hour post-dose	97.3 (1.2)	96.0 (1.6)	96.2 (2.0)
2 hours post-dose	97.1 (1.3)	95.8 (1.4)	95.8 (1.7)
4 hours post-dose	96.9 (1.4)	96.5 (1.2)	96.5 (1.5)
6 hours post-dose	97.1 (1.5)	96.7 (1.3)	96.7 (1.7)
11 hours post-dose	96.8 (1.4)	96.8 (1.4)	96.4 (1.5)
15 hours post-dose	96.7 (1.0)	96.5 (1.4)	97.1 (1.5)

22. Secondary Outcome

Title	Systolic and Diastolic Blood Pressure Assessments
Description	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).
Time Frame	Enrollment Visit; 15 hours post-dose

Outcome Measure Data

Analysis Population Description

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).

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

23. Secondary Outcome

Title	Change From Enrollment in 12-lead Electrocardiogram Parameters
Description	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.
Time Frame	Enrollment (pre-surgery); Discharge Visit

Outcome Measure Data

Analysis Population Description

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)

Arm/Group Title	ECG Changes: Adolescents	ECG Changes: Older Children	ECG Changes: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Children and Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children and Adolescents Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children and Adolescents Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Overall Number of Participants Analyzed	21	27	17
Mean (Standard Deviation); Unit of Measure: milliseconds
QTcF change	-3.6 (16.4)	15.7 (21.7)	5.6 (20.7)
QT Duration change	-8.0 (33.1)	8.5 (32.0)	-4.1 (29.6)
QRS Duration change	0.5 (4.5)	-0.2 (4.7)	0.5 (5.8)
PR Duration change	-3.5 (11.7)	-1.8 (11.3)	-2.4 (12.6)
RR Duration change	-32.2 (193.8)	-35.2 (156.5)	-48.1 (102.8)

24. Secondary Outcome

Title	Change From Enrollment in 12-lead Electrocardiogram Heart Rate Parameter
Description	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.
Time Frame	Enrollment; Discharge Visit

Outcome Measure Data

Analysis Population Description

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)

Arm/Group Title	ECG Heart Rate Change: Adolescents	ECG Heart Rate Change: Older Children	ECG Heart Rate Change: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Children and Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children and Adolescents Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children and Adolescents Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
Overall Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: beats per minute
	2.0 (16.4)	4.3 (16.2)	10.7 (16.4)

25. Secondary Outcome

Title	Treatment Emergent Adverse Events by Intensity
Description	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.
Time Frame	Baseline; 48 hours post dosing

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Number of TEAEs: Adolescents	Number of TEAEs: Older Children	Number of TEAEs: Young and Very Young Children
Arm/Group Description:	Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 12 years and less than 18 years of age.	Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 6 years and less than 12 years of age.	Tapentadol oral solution single dose (1mg/kg body weight). Participants aged 2 years and less than 6 years of age.
Overall Number of Participants Analyzed	21	28	17
Measure Type: Number; Unit of Measure: number of events
Total number of TEAEs	22	33	11
Total number of mild TEAEs	10	16	10
Total number of moderate TEAEs	12	17	1

26. Secondary Outcome

Title	Intake of Additional Analgesic Medication During the Trial
Description	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).
Time Frame	Baseline; 15 hours post dosing

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Adolescents With Supplementary Analgesic	Older Children With Supplementary Analgesic	Young and Very Young Children With Supplementary Analgesic
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Measure Type: Number; Unit of Measure: participants
Supplemental analgesic medication taken	12	18	15
Supplemental opioid analgesic taken	3	3	8
Supplemental non-opioid analgesic taken	12	18	15

27. Secondary Outcome

Title	Hematology Safety Laboratory Assessments: Hemoglobin Concentration
Description	The hemoglobin test is a commonly ordered blood test and was done as part of a complete blood count (CBC). It is routinely done before and after surgery to check for anemia, the presence of chronic kidney disease or other chronic medical problems. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit; Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visits 2 and 3: N=16 one participant with missing data at each of these visits).

Arm/Group Title	Hemoglobin Concentration: Adolescents	Hemoglobin Concentration: Older Children	Hemoglobin Concentration: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: g/L
Visit 1	151.10 (13.82)	140.04 (6.66)	127.47 (7.60)
Visit 2	145.67 (21.44)	128.64 (7.88)	121.75 (7.91)
Visit 3	139.00 (19.20)	126.54 (9.10)	117.00 (7.63)

28. Secondary Outcome

Title	Hematology Safety Laboratory Assessments: Hematocrit
Description	Hematocrit is a blood test that measures the percentage of the volume of whole blood that is made up of red blood cells (RBC). This measurement depends on the number of red blood cells and the size of red blood cells. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit; Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visits 2 and 3: N=16 one participant with missing data at each of these visits).

Arm/Group Title	Hematocrit: Adolescents	Hematocrit: Older Children	Hematocrit: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: fraction of blood volume
Visit 1	0.436 (0.037)	0.400 (0.018)	0.368 (0.018)
Visit 2	0.421 (0.060)	0.372 (0.024)	0.363 (0.023)
Visit 3	0.402 (0.054)	0.364 (0.025)	0.356 (0.022)

29. Secondary Outcome

Title	Hematology Safety Laboratory Assessments: Erythrocyte Mean Corpuscular Volume (Mean Corpuscular Volume)
Description	Erythrocyte Mean Corpuscular volume is a measurement of the average size of Red Blood Cells (RBC). It is also referred to as Mean Corpuscular Volume. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit; Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visits 2 and 3: N=16 one participant with missing data at each of these visits).

Arm/Group Title	Mean Corpuscular Volume: Adolescents	Mean Corpuscular Volume: Older Children	Mean Corpuscular Volume: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: fL
Visit 1	86.1 (2.9)	82.3 (3.1)	79.6 (3.6)
Visit 2	86.5 (2.1)	83.1 (3.5)	81.8 (3.7)
Visit 3	86.9 (3.5)	83.1 (3.5)	82.7 (3.6)

30. Secondary Outcome

Title	Hematology Safety Laboratory Assessments: Platelet Count
Description	Platelets are cell fragments that are vital for normal blood clotting. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit; Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visits 2 and 3: N=16 one participant with missing data at each of these visits).

Arm/Group Title	Platelet Count: Adolescents	Platelet Count: Older Children	Platelet Count: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: GI/L
Visit 1	297.0 (59.8)	347.1 (86.2)	357.4 (67.5)
Visit 2	266.1 (73.0)	303.4 (73.9)	312.6 (111.2)
Visit 3	263.9 (57.9)	316.9 (71.3)	307.3 (50.0)

31. Secondary Outcome

Title	Hematology Safety Laboratory Assessments: Leukocyte Concentration
Description	Leukocytes are also called white blood cells (WBC). These were measured to assess immune function. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit; Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visits 2 and 3: N=16 one participant with missing data at each visit).

Arm/Group Title	Leukocyte Concentration: Adolescents	Leukocyte Concentration: Older Children	Leukocyte Concentration: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: GI/L
Visit 1	6.631 (1.682)	7.594 (3.984)	6.555 (1.278)
Visit 2	8.537 (2.514)	12.509 (4.209)	10.751 (3.272)
Visit 3	10.052 (3.253)	14.806 (4.031)	13.160 (2.907)

32. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Blood Glucose Concentration
Description	A blood glucose test measures the amount of a sugar called glucose in blood. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit; Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).

Arm/Group Title	Blood Glucose Concentration: Adolescents	Blood Glucose Concentration: Older Children	Blood Glucose Concentration: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: mmol/L
Visit 1	4.77 (0.51)	4.81 (0.52)	5.01 (1.38)
Visit 2	5.10 (0.68)	6.39 (1.49)	5.89 (1.17)
Visit 3	5.51 (0.90)	5.69 (1.21)	4.90 (0.54)

33. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Blood Sodium Concentration
Description	Sodium is required by the body for the body to function properly. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit; Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).

Arm/Group Title	Blood Sodium Concentration: Adolescents	Blood Sodium Concentration: Older Children	Blood Sodium Concentration: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: mmol/L
Visit 1	140.9 (1.4)	140.4 (2.1)	139.3 (1.3)
Visit 2	140.3 (1.5)	138.4 (2.6)	139.1 (1.2)
Visit 3	138.1 (1.2)	138.7 (1.8)	138.8 (1.9)

34. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Blood Potassium Concentration
Description	Potassium is a mineral that the body needs to work normally. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit; Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).

Arm/Group Title	Blood Potassium Concentration: Adolescents	Blood Potassium Concentration: Older Children	Blood Potassium Concentration: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: mmol/L
Visit 1	4.20 (0.31)	4.20 (0.32)	4.09 (0.33)
Visit 2	3.90 (0.36)	3.83 (0.32)	4.04 (0.36)
Visit 3	3.94 (0.26)	3.93 (0.29)	3.93 (0.27)

35. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Blood Calcium Concentration
Description	All cells need calcium in order to function. In the study there were 3 planned safety blood draws for routine blood tests. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit; Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Older children Group at Visit 2: N=27 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).

Arm/Group Title	Blood Calcium Concentration: Adolescents	Blood Calcium Concentration: Older Children	Blood Calcium Concentration: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: mmol/L
Visit 1	2.455 (0.065)	2.482 (0.100)	2.519 (0.055)
Visit 2	2.268 (0.166)	2.267 (0.108)	2.343 (0.160)
Visit 3	2.359 (0.104)	2.266 (0.157)	2.369 (0.123)

36. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Blood Chloride Concentration
Description	Chloride with other electrolytes help keep the proper balance of body fluids and maintain the body's acid-base balance. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care
Time Frame	Enrollment Visit; Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Older children Group at Visit 2: N=27 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).

Arm/Group Title	Blood Chloride Concentration: Adolescents	Blood Chloride Concentration: Older Children	Blood Chloride Concentration: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: mmol/L
Visit 1	103.3 (1.9)	103.4 (2.2)	103.8 (1.7)
Visit 2	106.6 (2.2)	104.9 (2.8)	106.2 (3.0)
Visit 3	103.0 (2.2)	105.1 (2.6)	105.1 (2.4)

37. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Blood Phosphate Concentration
Description	Phosphate is needed by the body. This test was done to see how much phosphate is in the blood. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit; Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).

Arm/Group Title	Blood Phosphate Concentration: Adolescents	Blood Phosphate Concentration: Older Children	Blood Phosphate Concentration: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: mmol/L
Visit 1	1.384 (0.185)	1.560 (0.146)	1.689 (0.165)
Visit 2	1.234 (0.194)	1.248 (0.241)	1.412 (0.179)
Visit 3	1.500 (0.199)	1.535 (0.178)	1.611 (0.181)

38. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Blood Urea Nitrogen (BUN) Concentration
Description	This test is to measure the amount of urea nitrogen in the blood. It was used to test liver and kidney function. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit; Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).

Arm/Group Title	BUN Concentration: Adolescents	BUN Concentration: Older Children	BUN Concentration: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: mmol/L
Visit 1	4.55 (1.19)	4.47 (1.30)	5.15 (1.19)
Visit 2	4.54 (1.32)	4.38 (0.95)	4.19 (0.93)
Visit 3	3.88 (0.98)	4.31 (1.21)	4.11 (0.82)

39. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Creatinine Concentration
Description	Creatinine is removed from the body entirely by the kidneys. If kidney function is not normal, creatinine level increases in the blood. In the study there were 3 planned safety blood draws for routine blood tests. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit; Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).

Arm/Group Title	Creatinine Concentration: Adolescents	Creatinine Concentration: Older Children	Creatinine Concentration: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: µmol/L
Visit 1	73.3 (14.7)	49.5 (6.2)	35.6 (4.8)
Visit 2	67.8 (15.1)	44.1 (9.3)	31.6 (6.7)
Visit 3	68.6 (16.2)	41.5 (8.0)	33.0 (5.8)

40. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Aspartate Aminotransferase (AST) Enzyme Activity
Description	AST is considered to be one of the two most important tests to detect liver injury. During liver damage the enzyme is released into the blood. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit; Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Older children at Visits 2 and 3: N=26 two participants with missing data; Young and Very Young Children Group at Visits 1 and 3: N=16 one participant with missing data).

Arm/Group Title	AST Activity: Adolescents	AST Activity: Older Children	AST Activity: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: U/L
Visit 1	21.5 (5.1)	27.9 (6.5)	33.4 (3.8)
Visit 2	21.6 (4.5)	29.9 (5.1)	37.9 (7.5)
Visit 3	21.6 (12.9)	30.2 (7.2)	33.8 (4.4)

41. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Triglycerides Concentration
Description	Triglycerides are a group of fat. Triglycerides were measured as part of metabolic and cardiac assessments. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit; Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant data missing; Older children Visits 2 and 3: N=27 and N=26 one and two participant data missing; Young and Very Young Children Group at Visits 2 and 3: N=16 one participant data missing).

Arm/Group Title	Triglycerides Concentration: Adolescents	Triglycerides Concentration: Older Children	Triglycerides Concentration: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: mmol/L
Visit 1	1.118 (0.459)	1.129 (0.495)	1.223 (0.511)
Visit 2	0.666 (0.318)	0.499 (0.245)	0.556 (0.173)
Visit 3	0.634 (0.224)	0.646 (0.225)	0.789 (0.227)

42. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Serum Albumin Concentration
Description	Albumin is a protein made by the liver. Albumin prevents fluid leaking into the tissues. Albumin also transports many small molecules. Serum albumin was measured in the clear liquid portion of the blood called serum. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit; Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Older children N=27 at Visit 1; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).

Arm/Group Title	Albumin Concentration: Adolescents	Albumin Concentration: Older Children	Albumin Concentration: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: g/L
Visit 1	43.4 (2.5)	43.4 (3.0)	42.6 (2.4)
Visit 2	38.4 (3.1)	37.1 (2.5)	38.9 (3.4)
Visit 3	38.4 (2.8)	37.2 (3.5)	37.5 (3.3)

43. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Urate in the Blood
Description	Uric acid (urate is the salt) is a chemical created when the body breaks down substances called purines. Most urate dissolves in blood and travels to the kidneys. From there, it passes out in the urine. The test is used to determine kidney function. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit; Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).

Arm/Group Title	Urate: Adolescents	Urate: Older Children	Urate: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: µmol/L
Visit 1	301.62 (69.35)	228.32 (41.87)	214.82 (39.67)
Visit 2	305.57 (85.12)	225.39 (44.74)	205.65 (34.51)
Visit 3	291.45 (69.06)	213.68 (57.96)	195.94 (48.68)

44. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Calculated Glomerular Filtration Rate
Description	Glomerular filtration rate (GFR) was done to check how well the kidneys are working. It estimates how much blood passes through the glomeruli in the kidney each minute. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit; Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).

Arm/Group Title	Glomerular Filtration Rate: Adolescents	Glomerular Filtration Rate: Older Children	Glomerular Filtration Rate: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: mL/min/1.73m^2
Visit 1	133.6 (20.7)	133.9 (16.6)	141.5 (18.4)
Visit 2	146.6 (25.2)	155.1 (38.0)	166.9 (42.5)
Visit 3	142.6 (23.3)	158.7 (31.5)	164.0 (37.3)

45. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Urine Specific Gravity
Description	This test was used to test for the water balance and urine concentration. A urine sample was tested right away. A dipstick with a color-sensitive pad was used. The color the dipstick changes and the specific gravity of the urine was read off the color chart. In the study there were 2 planned safety urine collections. At Visit 1 in the enrollment period, after consent and assent obtained. The second sample was obtained at Visit 3 prior to discharge from the hospital. The discharge visit was as per standard of care.
Time Frame	Enrollment Visit and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Young and Very Young Children Group at Visits 1: N=9 thus 8 participants with missing data; at Visit 3: N=7 thus 10 participants with missing data).

Arm/Group Title	Specific Gravity Urine: Adolescents	Specific Gravity Urine: Older Children	Specific Gravity Urine: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: units on a scale
Visit 1	1.025 (0.007)	1.024 (0.004)	1.021 (0.007)
Visit 3	1.022 (0.007)	1.024 (0.004)	1.024 (0.002)

46. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Urine pH (Acid, Alkalinity) Test
Description	A urine sample was tested right away. A dipstick made with a color-sensitive pad was used. The color indicated the acidity of the urine. In the study there were 2 planned safety urine collections. At Visit 1 in the enrollment period, after consent and assent obtained. The second sample was obtained at Visit 3 prior to discharge from the hospital. The discharge visit was as per standard of care.
Time Frame	Enrollment Visit and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Young and Very Young Children Group at Visits 1: N=9 thus 8 participants with missing data; at Visit 3: N=7 thus 10 participants with missing data).

Arm/Group Title	Urine pH: Adolescents	Urine pH: Older Children	Urine pH: Young and Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: units on a scale
Visit 1	6.2 (0.5)	6.5 (0.4)	6.2 (0.6)
Visit 3	6.1 (0.2)	6.2 (0.4)	6.4 (0.9)

47. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Liver Function Test - Alanine Aminotransferase (ALT) Enzyme Activity
Description	This test was done in combination with other tests (such as AST, ALP, and bilirubin) to diagnose and monitor the liver function. In the study there were 3 planned safety blood draws for routine blood tests. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit, Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=19 two participants with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).

Arm/Group Title	ALT Activity: Adolescents	ALT Activity: Older Children	ALT Activity: Young & Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: U/L
Visit 1	16.2 (6.3)	15.9 (4.1)	16.4 (3.4)
Visit 2	14.1 (4.6)	15.7 (3.4)	17.9 (5.3)
Visit 3	14.2 (4.5)	15.4 (3.4)	17.1 (4.1)

48. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Liver Function Test - Gamma-Glutamyl Transferase (GGT) Enzyme Activity
Description	The gamma-glutamyl transferase (GGT) test was used in combination with the alkaline phosphatase (ALP) test. Both ALP and GGT can be elevated in bile duct or liver complications. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit, Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 2 and 3: N=20 one participant with missing data; Older Children at Visit 2: N=27 one participant with missing data; Young and Very Young Children Group at Visit 2: N=16 one participant with missing data).

Arm/Group Title	GGT Activity: Adolescents	GGT Activity: Older Children	GGT Activity: Young & Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: U/L
Visit 1	12.0 (4.0)	10.6 (2.9)	9.4 (1.7)
Visit 2	10.4 (3.9)	8.7 (2.0)	8.6 (1.9)
Visit 3	10.8 (4.2)	8.8 (1.9)	8.3 (2.0)

49. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Liver Function Test - Bilirubin Concentration
Description	Old red blood cells are replaced by new blood cells every day. Bilirubin is made by the body when the old blood cells are removed. The concentration of bilirubin in the blood measures liver function. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit, Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents-Visit 2 & 3: N=20 - 1 participant with data missing; Older Children-Visit 1 & 2: N=26 thus 2 participants with data missing; Young and Very Young Children-Visits 1 & 3: N=12 (5 with data missing) & at Visit 2 N=9 (8 with data missing).

Arm/Group Title	Bilirubin Concentration: Adolescents	Bilirubin Concentration: Older Children	Bilirubin Concentration: Young & Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: µmol/L
Visit 1	12.0 (7.0)	6.8 (3.5)	4.8 (1.8)
Visit 2	10.9 (7.8)	6.3 (2.3)	3.7 (1.0)
Visit 3	17.8 (10.8)	9.3 (4.5)	5.8 (2.6)

50. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Liver Function Test - Lactate Dehydrogenase (LDH) Enzyme Activity
Description	Lactate Dehydrogenase (LDH) was used to check for tissue damage. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit, Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Older Children at Visits 1 and 3: N=26 and at Visit 2 N=24 participants; Young and Very Young Children Group at Visits 1 and 3: N=16 participant with missing data).

Arm/Group Title	LDH Activity: Adolescents	LDH Activity: Older Children	LDH Activity: Young & Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: U/L
Visit 1	157.7 (23.0)	210.5 (31.7)	243.8 (23.3)
Visit 2	154.5 (27.9)	199.1 (27.2)	256.3 (36.8)
Visit 3	143.9 (28.8)	197.8 (28.5)	238.6 (24.6)

51. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Blood Protein Concentration
Description	The test was done to verify kidney and liver function. It is done in combination with the albumin test. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit, Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Older Children at Visit 2: N=27 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data).

Arm/Group Title	Protein Concentration: Adolescents	Protein Concentration: Older Children	Protein Concentration: Young & Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: g/L
Visit 1	72.3 (3.5)	73.3 (4.4)	68.6 (4.7)
Visit 2	64.2 (4.6)	61.8 (4.4)	62.1 (4.9)
Visit 3	64.9 (4.4)	62.1 (5.5)	61.8 (4.6)

52. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Creatine Kinase (CK) Enzyme Activity
Description	The creatine kinase (CK) test was used to detect inflammation of muscles. The test was done in combination with other tests. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit, Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Older children at Visit 1: N=27 (1 participant missing); Young and Very Young Children Group at Visit 3: N=16 one participant with missing data at this visit).

Arm/Group Title	CK Activity: Adolescents	CK Activity: Older Children	CK Activity: Young & Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: U/L
Visit 1	126.0 (66.0)	109.8 (31.7)	133.4 (35.2)
Visit 2	186.8 (216.2)	283.3 (158.5)	275.8 (87.5)
Visit 3	264.6 (564.4)	288.1 (214.8)	203.6 (84.5)

53. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Alkaline Phosphatase (ALP) Enzyme Activity
Description	The Alkaline Phosphatase activity was used to detect bone or hepatobiliary disease. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to study drug administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit, Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 2 and 3: N=20 one participant with missing data; Young and Very Young Children Group at Visits 3: N=16 one participant with missing data at this visit).

Arm/Group Title	ALP Activity: Adolescents	ALP Activity: Older Children	ALP Activity: Young & Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: U/L
Visit 1	124.7 (62.7)	240.0 (50.8)	230.1 (26.7)
Visit 2	114.7 (53.9)	207.5 (42.2)	210.2 (31.5)
Visit 3	107.6 (54.3)	204.1 (46.7)	199.2 (26.2)

54. Secondary Outcome

Title	Biochemistry Safety Laboratory Parameters: Triacylglycerol Lipase (TL) Enzyme Activity
Description	A triacylglycerol lipase test was done to check for pancreatic function. In the study there were 3 planned safety blood draws for routine blood tests. In the study there were 3 planned safety blood draws for routine blood tests: at Visit 1 (during the enrollment period, including surgery), at Visit 2 (prior to investigational medicinal product administration) and at Visit 3 (prior to discharge from the hospital). The discharge visit was as per standard of care.
Time Frame	Enrollment Visit, Visit 2 and Discharge Visit

Outcome Measure Data

Analysis Population Description

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

(Adolescents Group at Visit 3: N=20 one participant with missing data; Older Children N=27 at Visit 1 one participant with missing data; Young and Very Young Children Group at Visit 3: N=16 one participant with missing data at visit).

Arm/Group Title	TL Activity: Adolescents	TL Activity: Older Children	TL Activity: Young & Very Young Children
Arm/Group Description:	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	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 Number of Participants Analyzed	21	28	17
Mean (Standard Deviation); Unit of Measure: U/L
Visit 1	29.5 (10.5)	30.3 (9.4)	26.3 (8.7)
Visit 2	22.7 (8.3)	22.6 (8.8)	19.6 (6.3)
Visit 3	24.8 (18.3)	22.2 (9.2)	19.3 (6.0)

Adverse Events

Time Frame	Any adverse event that started on the intake of tapentadol up to 48 hours thereafter.
Adverse Event Reporting Description	For tapentadol oral solution, the therapeutic reach is defined as 48 hours after intake. The age groups reported were prespecified in the protocol.
Arm/Group Title	Adolescents	Older Children	Young and Very Young Children
Arm/Group Description	Single Dose of Tapentadol Oral Solution in Adolescents Age 12 to Less Than 18 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 6 to Less Than 12 Years. Tapentadol oral solution single dose (1mg/kg body weight).	Single Dose of Tapentadol Oral Solution in Children Age 2 to Less Than 6 Years. Tapentadol oral solution single dose (1mg/kg body weight).
All-Cause Mortality
	Adolescents	Older Children	Young and Very Young Children
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events
	Adolescents	Older Children	Young and Very Young Children
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/21 (0.00%)	1/28 (3.57%)	0/17 (0.00%)
Surgical and medical procedures
post-procedural hemorrhage * 1 [1]	0/21 (0.00%)	1/28 (3.57%)	0/17 (0.00%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 16.1; [1] Post-procedural hemorrhage occurred 6 days following tonsillectomy. Outside the therapeutic range of the investigational product.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	3.6%
	Adolescents	Older Children	Young and Very Young Children
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	12/21 (57.14%)	20/28 (71.43%)	6/17 (35.29%)
Eye disorders
Diplopia * 1	0/21 (0.00%)	1/28 (3.57%)	0/17 (0.00%)
Gastrointestinal disorders
Nausea * 1	6/21 (28.57%)	9/28 (32.14%)	1/17 (5.88%)
Vomiting * 1	3/21 (14.29%)	8/28 (28.57%)	0/17 (0.00%)
Enlarged uvula * 1	0/21 (0.00%)	0/28 (0.00%)	1/17 (5.88%)
Abdominal pain upper * 1	0/21 (0.00%)	0/28 (0.00%)	1/17 (5.88%)
Constipation * 1	0/21 (0.00%)	1/28 (3.57%)	0/17 (0.00%)
General disorders
Infusion site irritation * 1	0/21 (0.00%)	0/28 (0.00%)	1/17 (5.88%)
Vessel puncture site bruise * 1	0/21 (0.00%)	0/28 (0.00%)	1/17 (5.88%)
Pyrexia * 1	1/21 (4.76%)	1/28 (3.57%)	0/17 (0.00%)
Chest pain * 1	0/21 (0.00%)	1/28 (3.57%)	0/17 (0.00%)
Infections and infestations
Otitis media * 1	1/21 (4.76%)	0/28 (0.00%)	0/17 (0.00%)
Otitis media viral * 1	0/21 (0.00%)	1/28 (3.57%)	0/17 (0.00%)
Investigations
Cardiac murmur † 1	0/21 (0.00%)	0/28 (0.00%)	1/17 (5.88%)
Aspartate aminotransferase increased † 1	1/21 (4.76%)	0/28 (0.00%)	0/17 (0.00%)
Blood creatine phosphokinase increased † 1	1/21 (4.76%)	0/28 (0.00%)	0/17 (0.00%)
Nervous system disorders
Dizziness * 1	3/21 (14.29%)	3/28 (10.71%)	0/17 (0.00%)
Headache * 1	2/21 (9.52%)	0/28 (0.00%)	2/17 (11.76%)
Somnolence * 1	1/21 (4.76%)	1/28 (3.57%)	0/17 (0.00%)
Tremor * 1	1/21 (4.76%)	0/28 (0.00%)	0/17 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	0/21 (0.00%)	0/28 (0.00%)	2/17 (11.76%)
Nasal discomfort * 1	0/21 (0.00%)	0/28 (0.00%)	1/17 (5.88%)
Epistaxis * 1	0/21 (0.00%)	1/28 (3.57%)	0/17 (0.00%)
Skin and subcutaneous tissue disorders
Hyperhidrosis * 1	1/21 (4.76%)	0/28 (0.00%)	0/17 (0.00%)
Pruritus * 1	0/21 (0.00%)	1/28 (3.57%)	0/17 (0.00%)
Rash * 1	1/21 (4.76%)	0/28 (0.00%)	0/17 (0.00%)
Vascular disorders
Hot flush * 1	0/21 (0.00%)	1/28 (3.57%)	0/17 (0.00%)
† Indicates events were collected by systematic assessment; * Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 16.1

Limitations and Caveats

Another opioid may been given according to medical judgment/standard of care if the participant had persistent intolerable pain 2 hours or more after administration of tapentadol oral solution despite having received a non-opioid analgesic.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The sponsor reserves the right to review any publication pertaining to the trial before it is submitted for publication. Neither party has the right to prohibit publication unless publication can be shown to affect possible patent rights.

Results Point of Contact

• Name/Title: Director of Clinical Trials
• Organization: Grünenthal GmbH
• Phone: +49 241 569 3223
• EMail: Clinical-Trials@grunenthal.com

Publications of Results:

Muse D, Tarau E, Lefeber C, Sohns M, Brett M, Goldberg J, Rosenburg R. Pharmacokinetics, safety, and efficacy of tapentadol oral solution for treating moderate to severe pain in pediatric patients. J Pain Res. 2019 May 31;12:1777-1790. doi: 10.2147/JPR.S197039. eCollection 2019.

• Responsible Party: Grünenthal GmbH
• ClinicalTrials.gov Identifier: NCT01729728
• Other Study ID Numbers: KF5503/68; 2013-002016-27 ( EudraCT Number )
• First Submitted: November 6, 2012
• First Posted: November 20, 2012
• Results First Submitted: September 9, 2014
• Results First Posted: November 27, 2014
• Last Update Posted: November 4, 2019