Clinical Trials Register

Summary
EudraCT Number:	2010-020510-29
Sponsor's Protocol Code Number:	OTR1020
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-08-02
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2010-020510-29

A.3

Full title of the trial

An Open-label Study to Characterise the Pharmacokinetics and Safety of Oxycodone Hydrochloride q12h Controlled-Release Tablets (ORF) in Paediatric Patients Aged 6 to 16 Years Inclusive, Who Require Opioid Analgesia.

A.4.1

Sponsor's protocol code number

OTR1020

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Purdue Pharma L.P.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Oxycodone hydrochloride q12h controlled release Tablets
D.3.2	Product code	ORF
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Oxycodone hydrochloride
D.3.9.2	Current sponsor code	OTR1020
D.3.9.3	Other descriptive name	N/A
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Oxycodone hydrochloride q12h controlled release Tablets
D.3.2	Product code	ORF
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Oxycodone hydrochloride
D.3.9.2	Current sponsor code	OTR1020
D.3.9.3	Other descriptive name	N/A
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	15
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Oxycodone hydrochloride q12h controlled release Tablets
D.3.2	Product code	ORF
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Oxycodone hydrochloride
D.3.9.2	Current sponsor code	OTR1020
D.3.9.3	Other descriptive name	N/A
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Post operative and non-surgical paediatric patients, expected to or must have moderate to severe pain requiring oral opioid analgesic treatment for at least 24 hours. Patients must be inpatient for the treatment period of the study.

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
E.1.2	Level	LLT
E.1.2	Classification code	10002182
E.1.2	Term	Analgesia

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
E.1.2	Level	LLT
E.1.2	Classification code	10036276
E.1.2	Term	Postoperative analgesia

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objectives of this study are:

1. To characterise the pharamcokinetics (PK) of single-dose ORF tablets in paediatric patients aged 6 to 16 years, inclusive
2. To characterise the safety of ORF tablets in paediatric patients aged 6 to 16 years, inclusive.

E.2.2

Secondary objectives of the trial

The secondary objective of this study is to examine ORF multiple-dose pharmacokinetics (PK) in paediatric patients aged 6 to 16 years, inclusive.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Have written informed consent provided by the parent or legal guardian and patient assent, when appropriate.
2. Children of either gender, aged 6 to 16 years, inclusive.
3. Have or are expected to have moderate to severe pain requiring opioid analgesic treatment for at least 24 hours.
4. 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.
5. Must be inpatient for the treatment period of the study.
6. 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 IV morphine.
7. Have adequate pain control during the 6 hours prior to study drug administration, based on appropriate clinical assessment.
8. Must be sufficiently alert to communicate and complete the FPS-R or 100-mm VAS.
9. Females who are sexually active must be using an adequate and reliable method of contraception.
10. If female and of child bearing potential, must have a negative pregnancy test and be non-lactating.
11. Must be able to swallow tablets whole.
12. Must have stable vital signs.
13. Must have vascular access to facilitate blood draws.
14. 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.
15. Must be willing to have up to 10 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.

E.4

Principal exclusion criteria

1. Have any history of hypersensitivity or medical contraindication for the use of oxycodone (this does not exclude patients with a history of expected opioid-related AEs, such as light-headedness, dizziness, sedation, nausea, or vomiting).
2. Have 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).
3. Have received oxycodone in the 24 hours prior to study drug administration. (See Protocol Section 9.9, Excluded, Prior and Concomitant Medications and Therapies).
4. Have received epidural (or regional) anesthesia <12 hours prior to the first oral dose of ORF.
5. Have a current history of malabsorption syndrome.
6. Have a current diagnosis of sleep apnea within the last year.
7. Have reduced renal function (serum creatinine > 1.8 X the upper limit of normal for age).
8. Have 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.
9. Are currently taking any medications which are CYP3A4 inhibitors.
10. Have 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.
11. Have impaired cardiovascular stability (e.g., the day of surgery for cardiac surgery patients).
12. Are deemed to be unsuitable by the investigator for reason(s) not specifically stated in the exclusion criteria.

E.5 End points

E.5.1

Primary end point(s)

PK Analysis:

Descriptive statistics will be tabulated overall and by age group as applicable, for all plasma concentrations and PK metrics.
PK metrics related to exposure (AUCt, AUCtau, AUCinf, Cmax, Cmin, Cavg), non-normalized and normalized by body weight and dose, will be summarized using means and associated 95% confidence intervals (CIs).
For the normalized data, a general linear model approach will be utilized to provide a 90% CI for the ratio of oxycodone exposure metrics among pediatric age groups.
The PK data obtained in this pediatric population may be compared with previous data obtained in adults.

Safety and Pain Analysis:

All data (AEs, clinical laboratory results, vital signs, somnolence, SpO2) and pain (FPS-R, 100-mm-VAS) data will be listed for patients in the safety population. Results of clinical laboratory evaluations that lie outside the normal range will be flagged on the listings as high or low.
AE reported terms will be categorized into preferred terms and associated system organ class using the Medical Dictionary for Regulatory Activities. Treatment emergent AEs will be defined as AEs that start after. or increase in severity after. the first dose of ORF. Treatment-emergent AEs will be summarized by presenting the incidence of AEs overall and by age group, by the MedDRA preferred term, nested within system organ class for the safety population.
Laboratory data, vital signs, somnolence and SpO2 will be summarized overall and by age group, and by time point. Pain scores will be summarized overall and by age group, and by time point.
Summary tabulations for safety data will include incidence rates for respiratory depression and hypotension.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Pharmacokinetic

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Written informed consent for the study will be obtained from all patients’ parents/legal guardians.
Assent by the patient will be documented in accordance with the policies of the investigator’s IRB/EC and local regulations.

F.3.3.7

Others

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Peadiatric patients aged 6 to 16 years

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2010-08-25

Ethics Committee Opinion of the trial application

Not-Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Other

Date of Ethics Committee Opinion

2010-10-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-08-16

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