Efficacy and safety of multiple doses of tapentadol oral solution in the treatment of moderate to severe acute pain in children aged 2 to <18 years – a randomized, double-blind, placebo-controlled trial

Figures & data

Figure 1 Trial design.

Abbreviations: NCA, nurse-controlled analgesia; PCA, patient-controlled analgesia.

Table 1 Efficacy Outcome Measures

Outcome measure	Description
Amount of supplemental opioid analgesic medication	Morphine or hydromorphone administered via PCA/NCA
Pain intensity, assessed using age-appropriate rating scales
For patients 2 to <6 years or older children incapable of communicating their pain: Face, Legs, Activity, Cry, and Consolability (FLACC^Citation25) scale	Observational scale from 0 to 10 with 0=no pain
For patients 6 to <12 years: Faces Pain Scale-revised (FPS-R^Citation26)	Self-reporting 6-point scale Six faces with scores of 0, 2, 4, 6, 8, 10 where 0=no pain and 10=very much pain
For patients 12 to <18 years: Visual Analog Scale	Self-reporting 100 mm scale from 0=no pain to 100=worst imaginable pain
Clinical Global Impression of Change (CGIC^Citation27)	Investigator rating of patients’ overall improvement from 1=very much improved to 7=very much worse
Patient Global Impression of Change (PGIC^Citation27)	Patients or parents/guardians rating of overall change in patients’ health status from 1=very much improved to 7=very much worse
Palatability and acceptability of trial medication	5-point faces scale^Citation28 from really good/easy to really bad/really difficult

Abbreviations: NCA, nurse-controlled analgesia; PCA, patient-controlled analgesia.

Figure 2 Patient flow chart.

Notes: “Recovery” denotes that opioid analgesic medication is no longer required. “Physician decision” denotes the switch to exclusively oral opioid analgesic medication indicated according to local standard of care. ^aAll patients treated with study medication were included in the full analysis set and the safety set. ^bAll patients attended the follow-up visit and completed the trial.

Table 2 Demographic Data And Baseline Characteristics

	Placebo N=52	Tapentadol N=108	Overall N=160
Sex
Female	23 (44.2%)	53 (49.1%)	76 (47.5%)
Male	29 (55.8%)	55 (50.9%)	84 (52.5%)
Age group
2 to <6 years	12 (23.1%)	23 (21.3%)	35 (21.9%)
6 to <12 years	15 (28.8%)	32 (29.6%)	47 (29.4%)
12 to <18 years	25 (48.1%)	53 (49.1%)	78 (48.8%)
Body mass index (kg/m^2)	19.1±3.8	18.8±4.1	18.9±4.0
Duration of surgery (min)	203.9±155.8	186.0±110.5	191.9±126.8
Background infusion^a	15 (28.8%)	39 (36.1%)	54 (33.8%)
Intake of morphine or hydromorphone in the 24 hrs prior to trial medication (mg/kg^b)	0.45±0.7	0.59±1.2	0.55±1.1
Time between end of surgery and first dose of trial medication (min)	795.9±553	1018.9±1483.8	946.5±1261.3

Notes: Data are mean±standard deviation or number of patients (%). ^aMorphine or hydromorphone; ^bmorphine equivalents.

Figure 3 Least squares mean difference (95% CI) between the trial medications for the amount of supplemental opioid analgesic medication used within the first 24 hrs after intake of first trial medication.

Abbreviation: LSMD, least squares mean difference.

Figure 4 Mean pain intensity (±95% confidence interval) prior to each intake of trial medication (first seven intakes). (A) Face, Legs, Activity, Cry, and Consolability scale; (B) Faces Pain Scale-revised; (C) Visual Analog Scale.

Note: ^aAssessment was performed 30–60 mins after first intake of trial medication.
Abbreviations: FLACC, Face, Legs, Activity, Cry, and Consolability; FPS-R, Faces Pain Scale-revised; VAS, Visual Analog Scale.

Figure 5 Palatability (taste) and acceptance (swallowing) of the trial medication after first and last doses (full analysis set).

Figure 6 Clinical Global Impression of Change and Patient Global Impression of Change after completion of double-blind treatment (full analysis set).

Note: All patients above the dashed line reported improvement.
Abbreviations: CGIC, Clinical Global Impression of Change; PGIC, Patient Global Impression of Change.

Table 3 Treatment-Emergent Adverse Event Profile Of The Trial Population (Safety Set)

	Patients 2 to ≤6 Years			Patients 6 to ≤12 Years			Patients 12 To ≤18 Years			Entire patient population
	Placebo N=12	Tapentadol N=23	Overall N=35	Placebo N=15	Tapentadol N=32	Overall N=47	Placebo N=25	Tapentadol N=53	Overall N=78	Placebo N=52	Tapentadol N=108	Overall N=160
Any TEAE	5 (41.7%)	9 (39.1%)	14 (40%)	6 (40%)	15 (46.9%)	21 (44.7%)	15 (60%)	38 (71.7%)	53 (67.9%)	26 (50%)	62 (57.4%)	88 (55%)
Any serious TEAE	0	0	0	0	1 (3.1%)	1 (2.1%)	0	1 (1.9%)	1 (1.3%)	0	2 (1.9%)	2 (1.3%)
Any TEAE related to trial medication^a	1 (8.3%)	2 (8.7%)	3 (8.6%)	3 (20%)	10 (31.3%)	13 (27.7%)	7 (28%)	17 (32.1%)	24 (30.8%)	11 (21.2%)	29 (26.9%)	40 (25%)
Any TEAE causing discontinuation of treatment	0	1 (4.3%)	1 (2.9%)	0	2 (6.3%)	2 (4.3%)	2 (8%)	7 (13.2%)	9 (11.5%)	2 (3.8%)	10 (9.3%)	12 (7.5%)
Any TEAE in ≥5% of patients
Vomiting	0	4 (17.4%)	4 (11.4%)	1 (6.7%)	8 (25%)	9 (19.1%)	5 (20%)	13 (24.5%)	18 (23.1%)	6 (11.5%)	25 (23.1%)	31 (19.4%)
Nausea	0	2 (8.7%)	2 (5.7%)	0	2 (6.3%)	2 (4.3%)	4 (16%)	12 (22.6%)	16 (20.5%)	4 (7.7%)	16 (14.8%)	20 (12.5%)
Constipation	0	2 (8.7%)	2 (5.7%)	0	2 (6.3%)	2 (4.3%)	6 (24%)	7 (13.2%)	13 (16.7%)	6 (11.5%)	11 (10.2%)	17 (10.6%)
Pyrexia	0	2 (8.7%)	2 (5.7%)	1 (6.7%)	1 (3.1%)	2 (4.3%)	0	7 (13.2%)	7 (9%)	1 (1.9%)	10 (9.3%)	11 (6.9%)
Somnolence	0	1 (4.3%)	1 (2.9%)	0	1 (3.1%)	1 (2.1%)	2 (8%)	4 (3.9%)	6 (7.7%)	2 (3.8%)	6 (5.6%)	8 (5%)
Pruritus	1 (8.3%)	1 (4.3%)	2 (5.7%)	1 (6.7%)	1 (3.1%)	2 (4.3%)	1 (4%)	2 (3.8%)	3 (3.8%)	3 (5.8%)	4 (3.7%)	7 (4.4%)

Notes: Data are number of patients (%). ^aAt least possibly related in the opinion of the investigator.

Abbreviation: TEAE, treatment-emergent adverse event.

Merkel SI, Voepel-Lewis T, Shayevitz JR, Malviya S. The FLACC: a behavioral scale for scoring postoperative pain in young children. Pediatr Nurs. 1997;23:293–297.9220806

 PubMedGoogle Scholar

Hicks CL, von Baeyer CL, Spafford PA, van Korlaar I, Goodenough B. The faces pain scale-revised: toward a common metric in pediatric pain measurement. Pain. 2001;93:173–183. doi:10.1016/s0304-3959(01)00314-111427329

 PubMed Web of Science ®Google Scholar

Guy W. ECDEU assessment manual for psychopharmacology. (DHEW Publication no. ADM 76-338). Washington, DC: US Government Printing Office; 1976. doi:10.1084/jem.143.4.741

 Google Scholar

Guinard JX. Sensory and consumer testing with children. Trends Food Sci Technology. 2001;11(8):273–283. doi:10.1016/S0924-2244(01)00015-2

 Web of Science ®Google Scholar