Pharmacokinetics and Tolerability Study of Tapentadol for Postsurgical Pain in Children and Adolescents

• Conditions: Pain; MedDRA version: 14.1Level: PTClassification code 10033371Term: PainSystem Organ Class: 10018065 - General disorders and administration site conditions; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2010-020380-20-Outside-EU/EEA
• Lead Sponsor: Janssen Research & Development, L.L.C.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-03-09
• Last Update Posted: 11 March 2013

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Subjects must satisfy the following criteria to be enrolled in the study:
1. Male or female subject from 12 to less than 18 years of age (Part 1 only) or male or female subject from 6 to less than 18 years of age (Part 2 only). Age is determined on the day of dosing of study medication.
2. BMI below the 95th percentile for children, based on CDC growth charts
3. A maximum body weight of 85 kg.
4. Having completed scheduled surgery per investigator’s judgment such as examples provided here but not limited to tonsillectomy, minor orthopedic procedure, corrective spinal or thoracic orthopedic surgeries, peripheral soft tissue procedure, uncomplicated inguinal hernia repair, minor urogenital procedure, ear surgery, eye surgery, peripheral plastic, or cosmetic surgery. Other surgical procedures may be allowed, based on investigator’s judgment, that will not result in heavy blood loss and/or a long and difficult recovery period.
5. Having a postoperative pain intensity score = 4 on the McGrath CAS as a result of the scheduled surgical procedure.
6. If applicable, has signed an Assent Form as per local regulations.
7. Parent(s) or the legal guardian(s) of the subject signed an informed consent
document indicating that they understand the purpose of the study, the risks and benefits of the procedures required for the study and give permission for their child’s participation in the study.
8. If a female, is premenarchal, surgically incapable of childbearing, abstinent, or, if sexually active, is practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization)
before study entry and throughout the study.
9. If a female and postmenarchal or older than 12 years, has a negative urine pregnancy test on the day before or on the day of study drug administration.
10. If a male and sexually active, agrees to use an approved method of birth control to prevent pregnancy and, as applicable to relevant local regulations and medical practices, not to donate sperm from the day of study drug administration until 3 months afterwards.
11. Physical status rated as I or II as per the American Society of Anesthesiologists
(ASA) classification.
12. Is alert, oriented, able to follow commands, able to understand the study
requirements and procedures, and able to communicate intelligibly with the health care provider (taking into account his/her age).
13. As per investigator’s medical evaluation, is able to drink and tolerate oral fluids
and medication.
Are the trial subjects under 18? yes
Number of subjects for this age range: 40
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Has been previously enrolled in this study (ie, subjects enrolled in part 1 may not be enrolled in part 2 or vice versa).
2. The qualifying surgery involves a large body cavity (e.g. opening the abdominal, cardiac, or thoracic cavities and intervention of the organs therein).
3. The qualifying surgery required prolonged ventilation and/or intensive care.
4. The qualifying surgery is upper or lower airway surgery.
5. The qualifying surgery is brain surgery.
6. Has significant pulmonary, gastrointestinal, endocrine, metabolic, neurological, psychiatric disorders or any other clinically significant disease that in the Investigator's opinion may affect or compromise subject safety during the trial participation.
7. Paralytic ileus.
8. Fever within 1 week prior to tapentadol administration.
9. Mentally retarded, cognitively impaired or unable to comprehensively understand or follow the study instructions, as per investigator’s judgment or based on medical history
10. Subjects currently taking medications that may be associated with the occurrence of serotonin syndrome or seizures.
11. Subjects with conditions that may be associated with the occurrence of serotonin syndrome or seizures.
12. History of any one of the following:
a. seizure disorder or epilepsy
b. serotonin syndrome
c. mild or moderate traumatic brain injury, stroke, transient ischemic attack,or brain neoplasm within 1 year of screening
d. severe traumatic brain injury (consisting of 1 or more of the following: brain contusion; intracranial hematoma; or episode(s) of more than 24 hours duration of unconsciousness or posttraumatic amnesia) within 15 years of screening
e. Any traumatic or hypoxic brain injury resulting in ongoing sequelae suggesting transient changes in consciousness or symptoms suggestive thereof
f. moderate to severe renal or hepatic impairment
g. abnormal pulmonary function or respiratory disease (e.g., clinically relevant respiratory depression, acute or severe bronchial asthma, hypercapnia)
13. Has clinically relevant abnormal values for chemistry, hematology, or urinalysis
laboratory results at screening. The following specifications will apply:
a. >2 x ULN for AST or ALT,
b. >1.5 x ULN for total bilirubin,
c. >2 x ULN for creatinine,
d. other parameters as per the investigator’s judgment.
14. Has clinically relevant abnormal ECG as per the investigator’s judgment.
15. Requires concomitant use of sedatives, other than those used during surgery (diphenhydramine administered for itching is exempted from this requirement).
16. Has had postoperative analgesia supplied by a continuous regional technique (ie. nerve block”)or
subject-controlled epidural analgesia.
17. Has a history of alcohol and/or drug abuse in the investigator’s judgment, based
on subject’s history and physical examination. 18. Has received an experimental drug or used an experimental medical device within 30 days prior to study drug administration, or within a period less than 10 timesthe drug’s half-life, whichever is longer.
19. Has received a potent inducer of hepatic drug-metabolizing enzyme activity (eg, phenobarbital and rifampin) or neuroleptics, MAOIs, SSRIs, SNRIs,
TCAs, triptans, anticonvulsants, antiparkinsonian drugs, and any drug that impairs metabolism of serotonin within 14 days before the scheduled study drug administration.
20. Has received dextromethorphan within 2 days before the scheduled study drug administration.
21. Has had p

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the pharmacokinetic profile of Tapentadol and its major metabolite Tapentadol-O-glucuronide after administration of a single dose of Tapentadol oral solution (OS) 1 mg/kg in children and adolescents aged from 6 to less than 18 years after scheduled surgical procedures that routinely produce acute, moderate to severe post-surgical pain.;Secondary Objective: Safety and tolerability will be evaluated and the measurement of pain intensity will be explored.;Primary end point(s): The primary objective is to evaluate the PK profile of Tapentadol and its major metabolite Tapentadol-O-glucuronide after administration of a single dose of Tapentadol oral solution 1 mg/kg in children and adolescents aged from 6 to less than 18 years after scheduled surgical procedures that routinely produce acute, moderate to severe postsurgical pain.;Timepoint(s) of evaluation of this end point: PK samples will be taken post-dose at +15m, +30m, +1h, +2h, +4h, +6h, +11h, and +15h

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Safety and tolerability will be evaluated and the measurement of pain intensity will be explored.;Timepoint(s) of evaluation of this end point: Safety and tolerability will be evaluated continuously. Pain Intensity measurement will be performed as follows: immediately before PK blood sampling (+15m, +30m, +1h, +2h, +4h, +6h, +11h, and +15h) and prior to any supplemental analgesic medication.