Pharmacokinetics and Safety of ORF Tablets in Pediatric Patients

NCT01160614 | Completed Phase 1 Results

• 2 other identifiers: OTR10202010-020510-29
• Study Type: interventional
• Target: 30
• Locations: 4 countries
• Sites: 17

Brief Summary

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.

Conditions

Opioid Analgesia

Keywords

Pediatric; Post-operative; Nonsurgical; patients; Opioid

Outcome Measures

Primary Outcomes (12)

• Single-dose PK Metric: Area Under the Plasma Concentration-time Curve From Hour 0 to the Last Measurable Plasma Concentration [AUCt]

  Up to 24 hours

• Single-dose PK Metric: Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (AUCinf)

  Due to insufficient sampling, AUCinf was not estimated.

  Up to 24 hours

• Single-dose PK Metric: Maximum Observed Plasma Concentration (Cmax)

  Up to 24 hours

• Single-dose PK Metric: Time to Maximum Plasma Concentration (Tmax)

  Up to 24 hours

• Single-dose PK Metric: Apparent Terminal Phase Rate Constant (Lamda z)

  Due to insufficient sampling, Lamda z was not estimated.

  Up to 24 hours

• Single-dose PK Metric: Apparent Plasma Terminal Phase Half/Life (t1/2z)

  Due to insufficient sampling, t1/2z was not estimated.

  Up to 24 hours

• Single-dose PK Metric: Lag Time Was Estimated as the Time Point Immediately Prior to the First Measurable Plasma Concentration Value (Tlag)

  Due to insufficient sampling, tlag was not estimated.

  Up to 24 hours

• 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)

  Up to 12 hours

• 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)

  Up to 12 hours

• 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)

  Up to 12 hours

• 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)

  Due to insufficient sampling, tlag 0-12 was not estimated.

  Up to 12 hours

• The Number of Patients With Adverse Events as a Measure of Safety

  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).

Secondary Outcomes (1)

• Multiple-dose PK Metric: Minimum Observed Plasma Concentration Just Prior to the Next Dose (Cmin)

  Up to 72 hours if all 5 doses were administered

Study Arms (1)

ORF Tablets

EXPERIMENTAL

ORF Tablets

Drug: Oxycodone hydrochloride controlled-release (ORF) tablets

Interventions

Oxycodone hydrochloride controlled-release (ORF) tablets DRUG

Oxycodone hydrochloride controlled-release (ORF) tablets (10 mg, 15 mg or 20 mg) taken every 12 hours

ORF Tablets

Eligibility Criteria

• Age: 6 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Purdue Pharma LP: lead

Study Sites (17)

Maricopa Medical Center

Phoenix, Arizona, 85008, United States

Location

Arkansas Childrens Hospital

Little Rock, Arkansas, 72202-3591, United States

Location

LS Packard Children's Hospital

Palo Alto, California, 94304, United States

Location

The Children's Hospital Association

Aurora, Colorado, 80045, United States

Location

Research Facility

Miami, Florida, 33136, United States

Location

F3900 C.S. Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

The Children's Hospital at OUMC

Oklahoma City, Oklahoma, 73104-5070, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Children's Med Center of Dallas

Dallas, Texas, 75235, United States

Location

Scott & White Memorial Hospital & Clinic

Temple, Texas, 76508, United States

Location

University of Washington School of Medicine - Harborview Medical Center

Seattle, Washington, 98104-2420, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

The Royal Children's Hospital

Parkville, 3052, Australia

Location

Helsinki University Central Hospital/Children and Adolescent Hospital

Helsinki, 00290, Finland

Location

Kuopio University Hospital/Operative Services and Intensive Care

Kuopio, 70211, Finland

Location

Waikato Clinical Research (2008) Ltd

Hamilton, 3214, New Zealand

Location

MeSH Terms

Interventions

Open Reading Frames; Tablets

Intervention Hierarchy (Ancestors)

Reading Frames; Genetic Code; Genetic Structures; Genetic Phenomena; Gene Components; Genes; Genome Components; Genome; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Medical Services
• Organization: Purdue Pharma L.P.

888-726-7535, option 1

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2010
• First Posted: July 12, 2010
• Study Start: July 1, 2010
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: October 15, 2012
• Results First Posted: August 21, 2012

Record last verified: 2012-10

Locations

US (13); AU (1); NZ (1); FI (2)