A Study to Look at Tapentadol Oral Solution in Children and Adolescents in Pain

NCT02081391 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: KF5503/652012-004359-35
• Study Type: interventional
• Target: 216
• Locations: 10 countries
• Sites: 43

Brief Summary

The purpose of the study was to evaluate the efficacy of tapentadol oral solution, based on the total amount of supplemental opioid analgesic used over 12 hours or 24 hours after initiation of investigational medicinal product (IMP) in children and adolescents who had undergone surgery that would produce moderate to severe pain during opioid treatment.

Conditions

Acute Pain

Keywords

Acute Pain; Post-operative; Tapentadol; Opioid Treatment; Pediatric Participants

Outcome Measures

Primary Outcomes (2)

• For the US FDA: The Total Amount of Supplemental Opioid Analgesic Medication Used Within the First 12 Hours After First Intake of Investigational Medicinal Product (IMP) [Tapentadol Oral Solution or Placebo]

  The primary endpoint for the United States Food and Drug Administration (US FDA) (and secondary endpoint for the Pediatric Committee of the European Medicines Agency \[EU PDCO\]) was the total amount of supplemental opioid analgesic medication (SOAM) used in the Full Analysis Set (from 2 years to \<18 years old) within 12 hours after first intake of IMP. SOAM use is expressed in mg/kg of morphine i.v. equivalents.

  Up to 12 hours

• For the EU PDCO: The Total Amount of Supplemental Opioid Analgesic Medication Used Within the First 24 Hours After First Intake of IMP [Tapentadol Oral Solution or Placebo]

  The primary endpoint for the EU PDCO (and secondary endpoint for the US FDA) was the total amount of supplemental opioid analgesic medication (SOAM) used in the Full Analysis Set (from 2 years to \<18 years old) within 24 hours after first intake of IMP. SOAM use is expressed in mg/kg of morphine i.v. equivalents.

  Up to 24 hours

Secondary Outcomes (12)

• Total Amount of Supplemental Opioid Analgesic Medication Received, Assessed in 12-hour Intervals From 24 Hours to 96 Hours After the First Dose of IMP

  Up to 96 hours

• Palatability of IMP After First Dose Assessed Using Facial 5-point Hedonic Scale

  Up to 96 hours

• Acceptability of IMP After First Dose Assessed Using Facial 5-point Hedonic Scale

  Up to 96 hours

• Change From Baseline in the Face, Leg, Activity, Cry, and Consolability (FLACC) Total Score in Participants Aged Less Than 6 Years

  Up to 96 hours

• Change From Baseline Pain Intensity Using the Faces Pain Scale-Revised (FPS-R) in Participants Aged 6 to Less Than 12 Years

  Up to 96 hours

Other Outcomes (2)

• Mean Amount of Supplemental Opioid Analgesic Medication Use After First Intake of Investigational Medicinal Product in Children Aged From Birth to Less Than 2 Years

  Up to 24 hours

• Median Amount of Supplemental Opioid Analgesic Medication Use After First Intake of Investigational Medicinal Product in Children Aged From Birth to Less Than 2 Years

  Up to 24 hours

Study Arms (2)

Tapentadol immediate-release (IR)

EXPERIMENTAL

In the first 24 hours, tapentadol oral solution at a dose of 1.25 mg/kg body weight was given every 4 hours (±15 min) to participants aged 6 months to less than 18 years (maximum individual dose of tapentadol was 100 mg). Participants from 30 days to less than 6 months were dosed with 0.5 mg/kg body weight every 4 hours. Participants from birth to less than 30 days of age were dosed with 0.1 mg/kg body weight every 4 hours. After 24 hours and up to 72 hours, the dose could be reduced based on the investigator's judgment.

Drug: Tapentadol oral solution 4 mg/mL; Drug: Tapentadol oral solution 20 mg/mL

Placebo

PLACEBO COMPARATOR

Matching placebo oral solution was administered every 4 hours (±15 min) up to 72 hours.

Other: Placebo

Interventions

Tapentadol oral solution 4 mg/mL DRUG

Participants aged 6 months to less than 18 years old with a body weight below 20 kg received tapentadol oral solution 4 mg/mL by mouth every 4 hours for up to 72 hours. Participants from birth to less than 6 months received tapentadol oral solution, diluted 4 fold.

Tapentadol immediate-release (IR)

Tapentadol oral solution 20 mg/mL DRUG

Participants aged from 6 months to less than 18 years with a body weight greater than or equal to 20 kg received tapentadol oral solution 20 mg/mL by mouth every 4 hours for up to 72 hours.

Tapentadol immediate-release (IR)

Placebo OTHER

Matching placebo oral solution was administered by mouth every 4 hours up to 72 hours.

Placebo

Eligibility Criteria

• Age: 1 Day - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Informed consent, and if applicable assent, given according to local regulations.
• Male or female participant aged from birth (at least 37 weeks gestational age) to less than 18 years.
• A female participant must be pre-menarchal, or surgically incapable of childbearing, or sexually abstinent, or if a female participant is sexually active, then she must be practicing an effective method of birth control (e.g., prescription hormonal contraceptives, intra-uterine devices used according to the product's instruction, double-barrier methods) before trial entry and throughout the trial.
• A female participant must have a negative pregnancy test if aged 12 years or older, or is post-menarchal, or is sexually active.
• Participant has undergone surgery (other than brain surgery or gastrointestinal surgery expected to affect the absorption of tapentadol \[in the investigator's judgment\]) that, in the investigator's opinion, would reliably produce moderate to severe pain requiring opioid treatment for at least 24 hours after first dose of IMP. Participants must remain hospitalized until the End of Treatment Visit.
• Participant has received post-operative morphine or hydromorphone by NCA/PCA, with or without a background infusion of the same opioid, according to standard of care prior to allocation/randomization to IMP and participant is expected to require this morphine or hydromorphone by NCA/PCA after starting IMP.
• Participant is able to tolerate liquids at the time of allocation/randomization to IMP.

You may not qualify if:

• Participant, parent or the legal representative is an employee of the investigator or trial site, with direct involvement in the proposed trial or other trials under the direction of that investigator or trial site, or family member of the employees or the investigator.
• Participant has been previously exposed to tapentadol.
• Participant has received an experimental drug or used an experimental medical device within 28 days before allocation/randomization to IMP, or within a period less than 10 times the drug's half-life, whichever is longer.
• Participant has a history or current condition of any one of the following:
• Non-febrile seizure disorder.
• Epilepsy.
• Serotonin syndrome.
• Traumatic or hypoxic brain injury, brain contusion, stroke, transient ischemic attack, intracranial hematoma, post-traumatic amnesia, brain neoplasm, or episode(s) of unconsciousness of more than 24 hours.
• Participant has a history or current condition of any one of the following:
• Moderate to severe renal or hepatic impairment.
• Abnormal pulmonary function or clinically relevant respiratory disease (e.g., acute or severe bronchial asthma, hypercapnia).
• Participant has a concomitant disease or disorder (e.g., endocrine, metabolic, neurological, psychiatric, infection, febrile seizure, paralytic ileus) that in the opinion of the investigator may affect or compromise participant safety during the study participation.
• Participant has history of suicidal ideation or behavior.
• Participant is obese in the investigator's judgment. Obesity can be determined based on appropriate body mass index (BMI) charts or tables; e.g., a BMI above the 97th percentile for children based on the World Health Organization growth charts or the participant's weight is less than 2500 grams.
• Participant has a clinically relevant history of hypersensitivity, allergy, or contraindication to the supplemental opioid analgesic medication or tapentadol, or the excipients, or naloxone.

Sponsors & Collaborators

• Grünenthal GmbH: lead
• Depomed: collaborator

Study Sites (43)

US008

Little Rock, Arkansas, 72202, United States

Location

US004

Stanford, California, 94305, United States

Location

US011

Miami, Florida, 33136, United States

Location

US012

Louisville, Kentucky, 40202, United States

Location

US001

The Bronx, New York, 10461, United States

Location

US018

The Bronx, New York, 10467, United States

Location

US006

Durham, North Carolina, 27710, United States

Location

US016

Cincinnati, Ohio, 45229, United States

Location

US015

Philadelphia, Pennsylvania, 19104, United States

Location

US014

Pittsburgh, Pennsylvania, 15224, United States

Location

US003

Dallas, Texas, 75235, United States

Location

US005

Houston, Texas, 77030, United States

Location

US007

Milwaukee, Wisconsin, 53226, United States

Location

BG003

Pleven, 5800, Bulgaria

Location

BG005

Sofia, 1606, Bulgaria

Location

BG002

Stara Zagora, 600, Bulgaria

Location

HR003

Split, 21000, Croatia

Location

HR001

Zagreb, 10000, Croatia

Location

CZ004

Fryštát, 73506, Czechia

Location

CZ003

Olomouc, 77900, Czechia

Location

CZ001

Praha 4 - Krč, 14059, Czechia

Location

FR002

La Tronche, 38700, France

Location

FR001

Lille, 59037, France

Location

FR004

Limoges, 87000, France

Location

DE001

Freiburg im Breisgau, 79106, Germany

Location

HU004

Budapest, 1094, Hungary

Location

HU003

Debrecen, 4032, Hungary

Location

PL011

Bydgoszcz, 85-094, Poland

Location

PL010

Gdansk, 80-803, Poland

Location

PL005

Lodz, 93-338, Poland

Location

PL002

Lublin, 20-093, Poland

Location

PL009

Olsztyn, 10-561, Poland

Location

PL014

Rzeszów, 35-301, Poland

Location

PL007

Torun, 87-100, Poland

Location

PL004

Warsaw, 04-730, Poland

Location

PL008

Warsaw, 04-730, Poland

Location

ES002

Barcelona, 8950, Spain

Location

ES005

Madrid, 28040, Spain

Location

ES007

Madrid, 28046, Spain

Location

ES009

Santiago de Compostela, 15706, Spain

Location

ES006

Valladolid, 47003, Spain

Location

GB003

Bristol, BS2 8BJ, United Kingdom

Location

GB001

Sheffield, S10 2TH, United Kingdom

Location

Related Publications (1)

• Schwartz GJ, Feld LG, Langford DJ. A simple estimate of glomerular filtration rate in full-term infants during the first year of life. J Pediatr. 1984 Jun;104(6):849-54. doi: 10.1016/s0022-3476(84)80479-5.

  PMID: 6726515 BACKGROUND

MeSH Terms

Conditions

Acute Pain

Interventions

Tapentadol

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Limitations and Caveats

See primary endpoint for the US FDA.

Results Point of Contact

• Title: Clinical Trial Helpdesk
• Organization: Grünenthal GmbH

Clinical-Trials@grunenthal.com

+49 241 569

Study Officials

• Grünenthal Study Director

  Grünenthal GmbH

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The trial was double-blinded to prevent bias. The blind was broken for the participants aged 2 years to \<18 years (Pediatric Committee of the European Medicines Agency \[EU PDCO\] set) before recruitment of the \<6 month-old subjects for the United Sates Food and Drug Administration (US FDA) set (which comprised participants from birth to \<18 years) was completed. Participants not belonging to the EU PDCO set (\<2 years old) remained blinded (as independent randomization lists were used for participants aged \<2 years old) and were unblinded only after the data base was locked for all participants from birth to \<2 years old who were included in the US FDA \<2 years population.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2014
• First Posted: March 7, 2014
• Study Start: February 19, 2015
• Primary Completion: March 3, 2019
• Study Completion: March 14, 2019
• Last Updated: January 18, 2020
• Results First Posted: January 18, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

BU (3); HU (2); PL (9); ES (5); GB (2); US (13); FR (3); CZ (3); DE (1); CR (2)