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

NCT02221674 | Terminated Phase 2 Results DMC

• 4 other identifiers: KF5503-722014-000623-24U1111-1153-1662R331333PAI2007
• Study Type: interventional
• Target: 40
• Locations: 3 countries
• Sites: 7

Brief Summary

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.

Conditions

Moderate to Severe Acute Postoperative Pain

Keywords

Post-surgical pain; Opioid

Outcome Measures

Primary Outcomes (6)

• 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

  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 quantification (LLOQ). If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.

  Up to 8 hours after IMP administration

• 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

  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 quantification (LLOQ). If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.

  Up to 8 hours after IMP administration

• 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

  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 quantification (LLOQ). If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.

  Up to 8 hours after IMP

• 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

  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 limit of quantification (LLOQ). If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.

  Up to 8 hours after IMP

• 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

  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 limit of quantification (LLOQ). If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.

  Up to 8 hours after IMP

• 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

  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 limit of quantification (LLOQ). If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.

  Up to 8 hours after IMP

Other Outcomes (1)

• Change From Baseline (Visit 1, After Surgery) in Pain Intensity

  Baseline; up to 15 hours after study medication

Study Arms (1)

Tapentadol

EXPERIMENTAL

Tapentadol 4 mg/mL immediate release oral solution, single dose post-operatively.

Drug: Tapentadol

Interventions

Tapentadol DRUG

Also known as: Palexia®, Nucynta®, Yantil®

Tapentadol

Eligibility Criteria

• Age: 1 Day - 23 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• The participant's parent(s) or legal guardian(s) have given written informed consent to participate.
• Participant is not obese (e.g., a body weight above the 97th percentile for children based on the World Health Organization weight charts) with a minimum body weight of 2.5 kg.
• Physical status rated not higher than P3 on the American Society of Anesthesiologists physical status classification in participants aged from 1 month to less than 2 years.
• Participant has undergone surgery that, in the investigator's opinion, would reliably produce moderate to severe pain requiring opioid treatment.
• At the time of allocation to IMP, participant has a sedation score that is not higher than 2 (moderately sedated) on the University of Michigan Sedation Scale with the exception of participants who are mechanically ventilated in age subgroup 3, has a functioning gastrointestinal tract after surgery, and can tolerate medication administered orally or via a feeding tube at the time of allocation to IMP.
• Participant has a reliable venous vascular access for pharmacokinetic blood sampling.

You may not qualify if:

• The participant's parent(s) or legal guardian(s) is an employee of the investigator or trial site, with direct involvement in this trial or other trials under the direction of that investigator or trial site, or the participant, or participant's parent(s), or legal guardian(s) is a 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 to study medication, or within a period less than 10 times the drug's half-life, whichever is longer.
• Concomitant participation in another interventional clinical trial for the duration of this trial.
• Participant has undergone brain surgery.
• Participant has undergone a surgery that is expected to affect the absorption of tapentadol (e.g., to the gastrointestinal tract).
• Participant has a history or current condition of any one of the following:
• Seizure disorder.
• Traumatic or hypoxic brain injury, i.e. brain contusion, stroke, transient ischemic attack, intracranial bleeding or hematoma, brain neoplasm.
• Participant has a history or current condition of any one of the following:
• Moderate to severe renal impairment.
• Moderate to severe hepatic impairment, congestive hepatopathy, or hepatic portosystemic shunting.
• Clinically relevant abnormal pulmonary function or clinically relevant respiratory disease that in the opinion of the investigator would put the participant at risk for developing respiratory depression, unless the participant is mechanically ventilated in age subgroup 3.
• Participant has signs or symptoms of congestive heart failure (e.g., requiring more than minimal inotropic support, an abnormal lactic acid value greater than 2-times upper limit of normal), or hemorrhagic disorder following surgery.
• Minimal inotropic medication is defined as:

Sponsors & Collaborators

• Grünenthal GmbH: lead
• Depomed: collaborator

Study Sites (7)

US001

Palo Alto, California, 94305, United States

Location

US002

Louisville, Kentucky, 40202, United States

Location

US006

Durham, North Carolina, 27710, United States

Location

US004

Philadelphia, Pennsylvania, 19104, United States

Location

PL001

Lodz, 93-338, Poland

Location

PL004

Torun, 87-100, Poland

Location

GB001

Sheffield, S10 2TH, United Kingdom

Location

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Tapentadol

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Director of Clinical Trials
• Organization: Grünenthal GmbH

Clinical-Trials@grunenthal.com

+49 241 569

Study Officials

• Clinical Trial 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 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2014
• First Posted: August 20, 2014
• Study Start: November 5, 2014
• Primary Completion: October 14, 2016
• Study Completion: November 3, 2016
• Last Updated: January 29, 2018
• Results First Posted: December 12, 2017

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will share

Locations

GB (1); US (4); PL (2)