A Pharmacokinetic, Tolerability, and Safety Study of ULTRAM ER in Children With Pain

A Single Dose Pharmacokinetic, Tolerability, and Safety Study of ULTRAM ER at Two Dose Levels in Children Seven to Eleven Years Old, Inclusive, With Pain

The purpose of this study is to compare the pharmacokinetics (PK) of single oral doses of ULTRAM Extended Release (ER) at 2 dose levels in children between 7 and 11 years old, inclusive (up to 11 years 364 days) with pain due to injury or nonmalignant disease, to the PK in adults, with respect to the PK parameter AUC∞ (area under the curve) of racemic tramadol. PK explores how the drug is absorbed in the body, distributed within the body, and how it is removed from the body over time.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: ULTRAM ER; Drug: ULTRAM ER

Detailed Description

This is a multicenter, open-label (all people know the identity of the intervention), 2-group, single dose study. Within each group of participants for Parts 1 and 2, at least 1/3 of the participants will be female, at least 1/3 of the participants will be male, at least 1/3 of the participants will be below the age of 8 years, and at least 1/3 of the participants will be above the age of 10 years. Participants will be assigned to 1 group only. Each group of participants will receive a single oral dose of ULTRAM ER on 1 occasion. Group 1 will receive a dose of ULTRAM ER that is closest to 2 mg/kg, based on the participant's body weight and adjusting the dose in 25 mg increments. Following completion of all evaluations of Group 1, the pharmacokinetic data will be evaluated to target a dose for Group 2 that will achieve a level of exposure similar to that seen with a single 200 mg ULTRAM ER dose in adults. The maximum dose of ULTRAM ER should not exceed 6 mg/kg or 300 mg. When the study physician, the investigators, and the medical monitors agree that the PK of the drug is well-characterized and that the drug is well tolerated, enrollment will begin for Group 2 of the study. The sponsor's responsible Medical Officer will evaluate the safety of the calculated dose in Group 2 participants by evaluation of adverse drug events paying particular attention to events suggestive of either opioid toxicity or serotonin toxicity.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed need for control of pain due to injury or nonmalignant disease that does not influence fluid shifts and general drug disposition
• Weighs at least 20 kg
• Female participants must be premenarchal and in the opinion of the investigator not sexually active
• Able to swallow the intact tablet with the aid of water (participants may not chew, divide, dissolve, or crush the study drug)
• Signed informed consent document indicating that he/she understands the purpose of and procedures required for the study and is willing to participate in the study
• Informed consent signed by the parent(s) or the legal guardian(s) of the participant

Exclusion Criteria:

• History of or current clinically significant medical illness or condition including (but not limited to) cardiac disease, hematologic disease, coagulation disorders, lipid abnormalities, significant pulmonary disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, neurologic or psychiatric disease, infection, or any other illness or condition that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 2	Drug: ULTRAM ER; One dose of ULTRAM ER that is closest to 2 mg/kg, based on the participant's body weight and adjusting the dose in 25 mg increments.; Drug: ULTRAM ER; The target dose for Group 2 will be the one that achieves a level of exposure similar to that seen with a single 200 mg ULTRAM ER dose in adults.
Experimental: Group 1	Drug: ULTRAM ER; One dose of ULTRAM ER that is closest to 2 mg/kg, based on the participant's body weight and adjusting the dose in 25 mg increments.; Drug: ULTRAM ER; The target dose for Group 2 will be the one that achieves a level of exposure similar to that seen with a single 200 mg ULTRAM ER dose in adults.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The area under the curve (AUC∞) of ULTRAM ER as the primary PK parameter	At 1, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma concentration profile of ULTRAM ER	At 1, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose
Plasma concentration profiles of M1 and M5 metabolites	At 1, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose
Incidence of adverse events as a measure of safety and tolerability	48 hours post dose

Collaborators and Investigators

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Investigators: Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Clinical Trial, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: April 25, 2012
• First Submitted That Met QC Criteria: April 25, 2012
• First Posted (Estimate): April 26, 2012

Study Record Updates

• Last Update Posted (Estimate): August 29, 2012
• Last Update Submitted That Met QC Criteria: August 28, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Pain; Children; Tramadol hydrochloride; ULTRAM ER
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Tramadol
• Other Study ID Numbers: CR014014; TRAMAPPAI1002 (Other Identifier: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.)