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NCT02221674

Use of Tapentadol Oral Solution for Pain After Surgery in Children From Newborn to Less Than 2 Years Old

Terminated Phase 2 Results posted Last updated 29 January 2018
What this trial tests

Phase 2 trial testing Tapentadol in Moderate to Severe Acute Postoperative Pain in 40 participants. Terminated before completion.

Timeline
5 November 2014
Primary endpoint
14 October 2016
3 November 2016

Quick facts

Lead sponsorGrünenthal GmbH
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment40
Start date5 November 2014
Primary completion14 October 2016
Estimated completion3 November 2016
Sites7 locations across United Kingdom, United States, Poland

Drugs / interventions tested

Conditions studied

Sponsor

Grünenthal GmbH — full company profile →

Who can join

Adults 1 Day to 23 Months, any sex, with Moderate to Severe Acute Postoperative Pain. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Pharmacokinetic Evaluation Based on Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Participants Aged 6 Months to Less Than 2 Years Primary · Up to 8 hours after IMP administration

The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages. Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points. Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of Tapentadol were calculated. Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quant

30 minutes after administration
GroupValue95% CI
Participants Aged 6 Months to Less Than 2 Years - PK Set9.8± 5.21
1 hour after administration
GroupValue95% CI
Participants Aged 6 Months to Less Than 2 Years - PK Set18.79± NA
2 hours after administration
GroupValue95% CI
Participants Aged 6 Months to Less Than 2 Years - PK Set32.2± 14.92
4 hours after administration
GroupValue95% CI
Participants Aged 6 Months to Less Than 2 Years - PK Set11.1± 5.97
6 hours after administration
GroupValue95% CI
Participants Aged 6 Months to Less Than 2 Years - PK Set14.85± NA
8 hours after administration
GroupValue95% CI
Participants Aged 6 Months to Less Than 2 Years - PK Set10.7± 4.15
Pharmacokinetic Evaluation Based on Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Participants Aged 1 Month to Less Than 6 Months Primary · Up to 8 hours after IMP administration

The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages. Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points. Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of Tapentadol were calculated. Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quant

30 minutes after administration
GroupValue95% CI
Participants Aged 1 Month to Less Than 6 Months - PK Set8.3± 6.30
1 hour after administration
GroupValue95% CI
Participants Aged 1 Month to Less Than 6 Months - PK Set35.27± NA
2 hours after administration
GroupValue95% CI
Participants Aged 1 Month to Less Than 6 Months - PK Set27.3± 0.81
4 hours after administration
GroupValue95% CI
Participants Aged 1 Month to Less Than 6 Months - PK Set25.9± 10.33
6 hours after administration
GroupValue95% CI
Participants Aged 1 Month to Less Than 6 Months - PK Set32.75± NA
8 hours after administration
GroupValue95% CI
Participants Aged 1 Month to Less Than 6 Months - PK Set5.6± 1.81
Pharmacokinetic Evaluation Based on Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Participants Aged From Birth to Less Than 1 Month Primary · Up to 8 hours after IMP

The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages. Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points. Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of Tapentadol were calculated. Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quant

30 minutes after administration
GroupValue95% CI
Participants Aged From Birth to Less Than 1 Month - PK Set26.62± NA
1 hour after administration
GroupValue95% CI
Participants Aged From Birth to Less Than 1 Month - PK Set43.63± NA
2 hours after administration
GroupValue95% CI
Participants Aged From Birth to Less Than 1 Month - PK Set19.9± 7.67
4 hours after administration
GroupValue95% CI
Participants Aged From Birth to Less Than 1 Month - PK Set15.0± 8.92
6 hours after administration
GroupValue95% CI
Participants Aged From Birth to Less Than 1 Month - PK Set18.82± NA
8 hours after administration
GroupValue95% CI
Participants Aged From Birth to Less Than 1 Month - PK Set14.6± 6.26
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Participants Aged 6 Months to Less Than 2 Years Primary · Up to 8 hours after IMP

The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages. Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points. Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of tapentadol-O-glucuronide were calculated. Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower

30 minutes after administration
GroupValue95% CI
Participants Aged 6 Months to Less Than 2 Years - PK Set105.7± 125.00
1 hour after administration
GroupValue95% CI
Participants Aged 6 Months to Less Than 2 Years - PK Set430.7± NA
2 hours after administration
GroupValue95% CI
Participants Aged 6 Months to Less Than 2 Years - PK Set468.0± 248.41
4 hours after administration
GroupValue95% CI
Participants Aged 6 Months to Less Than 2 Years - PK Set348.7± 228.22
6 hours after administration
GroupValue95% CI
Participants Aged 6 Months to Less Than 2 Years - PK Set370.2± NA
8 hours after administration
GroupValue95% CI
Participants Aged 6 Months to Less Than 2 Years - PK Set285.1± 107.06
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Participants Aged 1 Month to Less Than 6 Months Primary · Up to 8 hours after IMP

The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages. Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points. Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of tapentadol-O-glucuronide were calculated. Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower

30 minutes after administration
GroupValue95% CI
Participants Aged 1 Month to Less Than 6 Months - PK Set128.8± NA
1 hour after administration
GroupValue95% CI
Participants Aged 1 Month to Less Than 6 Months - PK Set136.3± NA
2 hours after administration
GroupValue95% CI
Participants Aged 1 Month to Less Than 6 Months - PK Set324.9± 116.61
4 hours after administration
GroupValue95% CI
Participants Aged 1 Month to Less Than 6 Months - PK Set449.7± 7.42
6 hours after administration
GroupValue95% CI
Participants Aged 1 Month to Less Than 6 Months - PK Set253.3± NA
8 hours after administration
GroupValue95% CI
Participants Aged 1 Month to Less Than 6 Months - PK Set92.2± 63.83
Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Participants Aged From Birth to Less Than 1 Month Primary · Up to 8 hours after IMP

The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages. Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points. Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of tapentadol-O-glucuronide were calculated. Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower

30 minutes after administration
GroupValue95% CI
Participants Aged From Birth to Less Than 1 Month - PK Set74.38± NA
1 hour after administration
GroupValue95% CI
Participants Aged From Birth to Less Than 1 Month - PK Set209± NA
2 hours after administration
GroupValue95% CI
Participants Aged From Birth to Less Than 1 Month - PK Set98.5± 2.62
4 hours after administration
GroupValue95% CI
Participants Aged From Birth to Less Than 1 Month - PK Set147.6± 53.74
6 hours after administration
GroupValue95% CI
Participants Aged From Birth to Less Than 1 Month - PK Set224.8± NA
8 hours after administration
GroupValue95% CI
Participants Aged From Birth to Less Than 1 Month - PK Set174.1± 11.03
Change From Baseline (Visit 1, After Surgery) in Pain Intensity Secondary · Baseline; up to 15 hours after study medication

The change from baseline in pain intensity using the Face, Legs, Activity, Cry, Consolability Scale (FLACC Scale) at 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, and 15 hours after a single dose of tapentadol. The FLACC Scale is a behavioral scale for scoring postoperative pain in young children. It includes five categories of pain behaviors, including facial expression, leg movement, activity, cry, and consolability. The scale is scored in a range of 0-10 with 0 representing no pain. The pain intensity scores were summarized descriptively per scheduled time

15 minutes after administration
GroupValue95% CI
Participants Aged 6 Months to Less Than 2 Years.-0.8± 3.1
Participants Aged 1 Month to Less Than 6 Months.-1.3± 2.8
Participants Aged From Birth to Less Than 1 Month.-1.6± 1.5
30 minutes after administration
GroupValue95% CI
Participants Aged 6 Months to Less Than 2 Years.-1.1± 2.6
Participants Aged 1 Month to Less Than 6 Months.-3.0± 3.6
Participants Aged From Birth to Less Than 1 Month.-1.4± 1.5
1 hour after administration
GroupValue95% CI
Participants Aged 6 Months to Less Than 2 Years.-2.0± 3.6
Participants Aged 1 Month to Less Than 6 Months.-2.7± 4.5
Participants Aged From Birth to Less Than 1 Month.0.0± 3.7
2 hours after administration
GroupValue95% CI
Participants Aged 6 Months to Less Than 2 Years.-2.8± 2.9
Participants Aged 1 Month to Less Than 6 Months.-3.0± 3.9
Participants Aged From Birth to Less Than 1 Month.-0.4± 2.6
4 hours after administration
GroupValue95% CI
Participants Aged 6 Months to Less Than 2 Years.-1.6± 3.4
Participants Aged 1 Month to Less Than 6 Months.-2.2± 3.3
Participants Aged From Birth to Less Than 1 Month.-0.4± 2.3
6 hours after administration
GroupValue95% CI
Participants Aged 6 Months to Less Than 2 Years.-1.9± 3.1
Participants Aged 1 Month to Less Than 6 Months.-1.7± 4.8
Participants Aged From Birth to Less Than 1 Month.-0.4± 2.3
8 hours after administration
GroupValue95% CI
Participants Aged 6 Months to Less Than 2 Years.-2.5± 2.5
Participants Aged 1 Month to Less Than 6 Months.-3.0± 3.2
Participants Aged From Birth to Less Than 1 Month.-1.2± 1.1
12 hours after administration
GroupValue95% CI
Participants Aged 6 Months to Less Than 2 Years.-2.4± 2.8
Participants Aged 1 Month to Less Than 6 Months.-3.5± 3.8
Participants Aged From Birth to Less Than 1 Month.-1.4± 1.5

Adverse events — posted to ClinicalTrials.gov

Time frame: Any Adverse Events (AE) that started on the intake of the IMP (investigational medicinal product) up to the end of the therapeutic reach of the IMP. Any pre-treatment AE which worsened (change in intensity, frequency or quality) after IMP administration compared to the complaint present before IMP intake have been recorded as a new AE.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Participants Aged 6 Months to Less Than 2 Years.
Serious: 0/8 (0%)
Deaths: 0/8
Participants Aged 1 Month to Less Than 6 Months.
Serious: 0/6 (0%)
Deaths: 0/6
Participants Aged From Birth to Less Than 1 Month.
Serious: 0/5 (0%)
Deaths: 0/5
Other adverse events (12 terms — click to expand)

ReactionSystemParticipants Aged 6 Months…Participants Aged 1 Month …Participants Aged From Bir…
VomitingGastrointestinal disorders
Junctional ectopic tachycardiaCardiac disorders
Abdominal distensionGastrointestinal disorders
PyrexiaGeneral disorders
Stoma site erythemaInjury, poisoning and procedural complications
Wound dehiscenceInjury, poisoning and procedural complications
Blood creatine phosphokinase increasedInvestigations
Blood potassium decreasedInvestigations
Oxygen saturation decreasedInvestigations
Renal failureRenal and urinary disorders
TachypnoeaRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders

Data from ClinicalTrials.gov NCT02221674 adverse events section.

Sponsor's own description

This is a multicenter, open-label (all people involved know the identity of the intervention), single dose trial to evaluate the pharmacokinetic (PK) profile (how drugs are absorbed in the body, how are they distributed within the body and how are they removed from the body over time) in children aged from birth to less than 2 years after a surgical procedure that routinely produces moderate to severe acute post-surgical pain. The trial will also evaluate the safety and tolerability of tapentadol oral solution in the population studied and the effect of tapentadol oral solution on pain.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Tapentadol for the Treatment of Moderate-to-Severe Acute Pain in Children Under the Age of Two Years.
    Eissa A, Tarau E, Beuter C, Radic T, et al · · 2021 · cited 8× · PMID 33542653 · DOI 10.2147/jpr.s269530
  2. Population Pharmacokinetics of Tapentadol in Children from Birth to <18 Years Old.
    Khalil F, Choi SL, Watson E, Tzschentke TM, et al · · 2020 · cited 7× · PMID 33262645 · DOI 10.2147/jpr.s269549

Verify or expand the search:

Other trials of Tapentadol

Trials testing the same drug.

Other Grünenthal GmbH trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing