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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Pain

Intervention / Treatment
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* Drug: ULTRAM ER
* Drug: ULTRAM ER


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br> | Drug: ULTRAM ER<br>* 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.<br>|
| Experimental: Group 2<br> | Drug: ULTRAM ER<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, ULTRAM ER, Tramadol hydrochloride, Children