Pharmacokinetics and Safety of ORF Tablets in Pediatric Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Purdue Pharma LP
ClinicalTrials.gov Identifier:
NCT01160614
First received: July 8, 2010
Last updated: October 11, 2012
Last verified: October 2012
  Purpose

The purpose of this study is to characterize the pharmacokinetics (PK) of single-dose ORF tablets in pediatric patients aged 6 to 16 years, inclusive.


Condition Intervention Phase
Opioid Analgesia
Drug: Oxycodone hydrochloride controlled-release (ORF) tablets
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: An Open-label Study to Characterize the Pharmacokinetics and Safety of Oxycodone Hydrochloride q12h Controlled-Release (ORF) Tablets in Pediatric Patients Aged 6 to 16 Years Inclusive, Who Require Opioid Analgesia

Resource links provided by NLM:


Further study details as provided by Purdue Pharma LP:

Primary Outcome Measures:
  • Single-dose PK Metric: Area Under the Plasma Concentration-time Curve From Hour 0 to the Last Measurable Plasma Concentration [AUCt] [ Time Frame: Up to 24 hours ] [ Designated as safety issue: No ]
  • Single-dose PK Metric: Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (AUCinf) [ Time Frame: Up to 24 hours ] [ Designated as safety issue: No ]
    Due to insufficient sampling, AUCinf was not estimated.

  • Single-dose PK Metric: Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Up to 24 hours ] [ Designated as safety issue: No ]
  • Single-dose PK Metric: Time to Maximum Plasma Concentration (Tmax) [ Time Frame: Up to 24 hours ] [ Designated as safety issue: No ]
  • Single-dose PK Metric: Apparent Terminal Phase Rate Constant (Lamda z) [ Time Frame: Up to 24 hours ] [ Designated as safety issue: No ]
    Due to insufficient sampling, Lamda z was not estimated.

  • Single-dose PK Metric: Apparent Plasma Terminal Phase Half/Life (t1/2z) [ Time Frame: Up to 24 hours ] [ Designated as safety issue: No ]
    Due to insufficient sampling, t1/2z was not estimated.

  • Single-dose PK Metric: Lag Time Was Estimated as the Time Point Immediately Prior to the First Measurable Plasma Concentration Value (Tlag) [ Time Frame: Up to 24 hours ] [ Designated as safety issue: No ]
    Due to insufficient sampling, tlag was not estimated.

  • Single- and Multiple-dose PK Metric: Mean Area Under the Plasma Concentration During Each Dosing Interval-time Curve From Hour 0 to 12 Hours of the First Dose of ORF (AUC 0-12) [ Time Frame: Up to 12 hours ] [ Designated as safety issue: No ]
  • Single- and Multiple-dose PK Metric: Maximum Observed Plasma Concentration From Hour 0 to 12 Hours of the First Dose of ORF (Cmax 0-12) [ Time Frame: Up to 12 hours ] [ Designated as safety issue: No ]
  • Single- and Multiple-dose PK Metric: Time to Maximum Plasma Concentration From Hour 0 to 12 Hours of the First Dose of ORF (Tmax 0-12) [ Time Frame: Up to 12 hours ] [ Designated as safety issue: No ]
  • Single- and Multiple-dose PK Metric: Lag Time Estimated as the Time Point Immediately Prior to the First Measurable Plasma Concentration Value From Hour 0 to 12 Hours of the First Dose of ORF (Tlag 0-12) [ Time Frame: Up to 12 hours ] [ Designated as safety issue: No ]
    Due to insufficient sampling, tlag 0-12 was not estimated.

  • The Number of Patients With Adverse Events as a Measure of Safety [ Time Frame: Adverse events (AEs) & serious adverse events (SAEs) were reported from start of study participation through the period beyond study completion (AEs) & through 30 days following last study drug dose, or until last study visit, whichever was later (SAEs). ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Multiple-dose PK Metric: Minimum Observed Plasma Concentration Just Prior to the Next Dose (Cmin) [ Time Frame: Up to 72 hours if all 5 doses were administered ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: July 2010
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ORF Tablets
ORF Tablets
Drug: Oxycodone hydrochloride controlled-release (ORF) tablets
Oxycodone hydrochloride controlled-release (ORF) tablets (10 mg, 15 mg or 20 mg) taken every 12 hours

  Eligibility

Ages Eligible for Study:   6 Years to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent provided by the parent or legal guardian and patient assent, when appropriate.
  • Children of either gender, aged 6 to 16 years, inclusive.
  • Have or are expected to have moderate to severe pain for an extended period of time requiring inpatient opioid analgesic treatment for at least 12 hours as this is the minimum duration of study period treatment.
  • In order to receive the first oral dose, patients must have respiratory stability, including a sustained SpO2 of at least 92% with or without supplemental oxygen during the 15 minute period just prior to dosing.
  • Must be inpatient for the treatment period of the study.
  • The patient's anticipated opioid analgesic requirement over the first 12 hours that will follow administration of ORF must be equivalent to at least 10 mg of intravenous (IV) morphine.
  • Have adequate pain control during the 6 hours prior to study drug administration, based on appropriate clinical assessment.
  • Must be sufficiently alert to communicate and complete the faces pain scales-revised (FPS-R) or 100-mm visual analogue scale (VAS).
  • Females who are of child bearing potential must be using an adequate and reliable method of contraception (e.g., barrier with additional spermicidal foam or jelly, intra-uterine device, hormonal contraception) or be abstinent.
  • If female, must have a negative pregnancy test and be non-lactating.
  • Must be able to swallow tablets whole.
  • Must have stable vital signs.
  • Must have vascular access to facilitate blood draws.
  • Must be willing and able to participate in all aspects of this study involving use of oral medications, patient evaluation, and phlebotomy, as evidenced by written informed consent from the parent or legal guardian and written patient assent when required by the local IRB/EC.
  • Must be willing to have up to 10 milliliters (mL) of blood collected for blood analysis (7 mL for primary PK and 3 mL for secondary PK analysis); and up to 10 mL of blood for pre-specified safety laboratory tests, without safety concerns.
  • Must be treated with an opioid for a minimum of 96 hours prior to first dose of ORF.

Exclusion Criteria:

  • Any history of hypersensitivity or medical contraindication for the use of oxycodone (this does not exclude patients with a history of expected opioid-related adverse events (AEs), such as light-headedness, dizziness, sedation, nausea, or vomiting).
  • Any current history of medical or surgical conditions that might significantly interfere with the gastrointestinal absorption, distribution, metabolism, or excretion of oxycodone (this includes any history of serious disease+ of the gastrointestinal tract, liver, kidneys, and/or blood-forming organs).
  • Received oxycodone in the 24 hours prior to study drug administration. .
  • Received epidural (or regional) anesthesia < 12 hours prior to the first oral dose of ORF.
  • A current history of malabsorption syndrome.
  • A current diagnosis of sleep apnea within the last year.
  • Reduced renal function (serum creatinine > 1.8 X the upper limit of normal for age).
  • Hepatic impairment as evidenced by serum alanine amino transferase (ALT) or serum aspartate amino transferase (AST) > 5 times the upper limit of normal (ULN) for age.
  • Currently taking any medications which are CYP3A4 inhibitors.
  • Impaired respiratory reserve including severe acute or chronic lung disease, or patients receiving mechanical respiratory support, including mechanical ventilation, BIPAP, or CPAP 6 hours prior to the first oral dose and during the entire oral treatment period.
  • Impaired cardiovascular stability (e.g., the day of surgery for cardiac surgery patients).
  • Participated in a clinical drug study within 30 days preceding the initial dose in this study.
  • Patients who have had surgery within 96 hours prior to the day of the first dose of study drug.
  • Deemed to be unsuitable by the investigator for reason(s) not specifically stated in the exclusion criteria.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01160614

Locations
United States, Arizona
Maricopa Medical Center
Phoenix, Arizona, United States, 85008
United States, Arkansas
Arkansas Childrens Hospital
Little Rock, Arkansas, United States, 72202-3591
United States, California
LS Packard Children's Hospital
Palo Alto, California, United States, 94304
United States, Colorado
The Children's Hospital Association
Aurora, Colorado, United States, 80045
United States, Florida
Research Facility
Miami, Florida, United States, 33136
United States, Michigan
F3900 C.S. Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109
United States, Ohio
Akron Children's Hospital
Akron, Ohio, United States, 44308
United States, Oklahoma
The Children's Hospital at OUMC
Oklahoma City, Oklahoma, United States, 73104-5070
United States, Pennsylvania
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15224
United States, Texas
Children's Med Center of Dallas
Dallas, Texas, United States, 75235
Scott & White Memorial Hospital & Clinic
Temple, Texas, United States, 76508
United States, Washington
University of Washington School of Medicine - Harborview Medical Center
Seattle, Washington, United States, 98104-2420
United States, Wisconsin
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Australia
The Royal Children's Hospital
Parkville, Australia, 3052
Finland
Helsinki University Central Hospital/Children and Adolescent Hospital
Helsinki, Finland, 00290
Kuopio University Hospital/Operative Services and Intensive Care
Kuopio, Finland, 70211
New Zealand
Waikato Clinical Research (2008) Ltd
Hamilton, New Zealand, 3214
Sponsors and Collaborators
Purdue Pharma LP
  More Information

Additional Information:
No publications provided

Responsible Party: Purdue Pharma LP
ClinicalTrials.gov Identifier: NCT01160614     History of Changes
Other Study ID Numbers: OTR1020, 2010-020510-29
Study First Received: July 8, 2010
Results First Received: July 17, 2012
Last Updated: October 11, 2012
Health Authority: United States: Food and Drug Administration
Finland: Finnish Medicines Agency
New Zealand: Medsafe
Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Purdue Pharma LP:
Pediatric
Post-operative
Nonsurgical
patients
Opioid

Additional relevant MeSH terms:
Oxycodone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014