OxyNorm® Capsules (Immediate-Release) Pharmacokinetic (PK) Study

Phase 1

Completed

Conditions: Pain

Interventions: Drug: Oxycodone hydrochloride

Registration Number: NCT01643772

Lead Sponsor: Mundipharma (China) Pharmaceutical Co. Ltd

Brief Summary: A Single Dose PK Study of OxyNorm® immediate-release capsules 5, 10, and 20mg, and a multiple-dose PK Study of OxyNorm® immediate-release capsules 10mg in Chinese patients with pain.It will be a single center, open label, randomized, oral administration study.

Detailed Description: Single dose: The subjects will be randomized to receive a single dose of OxyNorm® immediate-release capsules 5, 10, and 20mg.

Multiple dose: The subjects will take 3 days OxyNorm® capsule 10mg, once every 6 hours, 10mg per dose. In the morning of the 4th day, the subjects will take single dose of OxyNorm® capsule 10mg. On the 5th day, all the subjects complete the study.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 61

Inclusion Criteria

Patients with pain, Multiple dose group should enroll the Patients with cancer pain;
Patients aged >≥30 to ≤ 60 years;
Body weight ≥ 45kg, and BMI range ≥19, <24;
Karnofsky score ≥ 70;
The results of liver function and kidney tests must meet the following criteria: ALT、AST is within the upper limit of normal value ranges by a factor 2, and TB、BUN、Cr is within the upper limit of normal value ranges by a factor 1.25;
The electrocardiogram examination results are normal;
Patients must have given a written informed consent prior to this trial, and have the capability to complete every required test.

Exclusion Criteria

Have hypersensitivity history to any opioids;
Have known hypersensitivity to any of compositions of the study drugs;
Patients who are likely to have paralytic ileus or acute abdomen or to perform an operation on abdominal region；
Patients with respiratory depression, cor pulmonale, or chronic bronchial asthma;
Patients who are unable to stop taking monoamine oxidase inhibitor during this trial period or time lapses less than 2 weeks since drug withdrawal;
Patients with hypercarbia;
Patients with biliary tract diseases, pancreatitis, prostatic hypertrophy, or corticoadrenal insufficiency;
Patients with alcoholism or drug abuse history;
Positive anti-HIV or syphilis antibody test result;
Patients who are pregnant, or lactating;
Urine screening before study is positive for opioids, barbiturates, amphetamines, cocaine metabolites, methadone, diazepam and cannabinoids;
Donated 400 mL or more of blood or blood products within 3 months prior to the start of the study, or donated 200 mL or more of blood or blood products within one month prior to the start of the study;
Subjects who participated in a clinical research study within one month of study entry;
Patients who are currently taking opioids.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Oxycodone Hydrochloride 20 mg Capsules	Oxycodone hydrochloride	Group 3: single dose Oxycodone Hydrochloride 20 mg Capsules after 10 hours fasting
Oxycodone Hydrochloride 10 mg Capsules(multi-dose)	Oxycodone hydrochloride	Group 4: multi-dose 4 times per day Oxycodone Hydrochloride 10mg Capsules for 3 days, and one dose on 4th day morning
Oxycodone Hydrochloride 10 mg Capsules	Oxycodone hydrochloride	Group 2: single dose Oxycodone Hydrochloride 10 mg Capsules after 10 hours fasting
Oxycodone Hydrochloride 5 mg Capsules	Oxycodone hydrochloride	Group 1: single dose Oxycodone Hydrochloride 5 mg Capsules after 10 hours fasting

Primary Outcome Measures

Name	Time	Method
Cmax,Clast for Participants Who Received a Single Dose	blood sample at predose,15min,30min,45min,1,1.5,2,3,4,6,8,12,24hr post-dose.	To calculate Cmax,Clast of Oxycondone,Noroxycodone,Hydroxymorphine, Normethoxymorphone with Non-atrioventricular model method in single dose 5mg,10mg,20mg.
AUC0-t and AUC0-∞ for Participants Who Received a Single Dose	blood sample at predose,15min,30min,45min,1,1.5,2,3,4,6,8,12,24hr post-dose.	To calculate AUC0-t AUC0-∞of Oxycondone,Noroxycodone,Hydroxymorphine, Normethoxymorphone with Non-atrioventricular model method.Plasma concentrations of Oxycodone Hydrochloride single dose 5mg,10mg,20mg will be analyzed.
AUCss for Participants Who Received Multiple Dose	Predose for the 1st, 2nd, 3rd day and predose,15min,30min,45min,1,1.5,2,3,4,6,8,12,24 post dose on the 4th day.	To calculate AUCss of Oxycondone,Noroxycodone,Hydroxymorphine, Normethoxymorphone with Non-atrioventricular model method in multiple dose 10mg.
CL for Participants Who Received Multiple Dose	Predose for the 1st, 2nd, 3rd day and predose,15min,30min,45min,1,1.5,2,3,4,6,8,12,24 post dose on the 4th day.	To calculate Clearance rate (CL) of Oxycondone,Noroxycodone,Hydroxymorphine, Normethoxymorphone with Non-atrioventricular model method in multiple dose 10mg.
The Excretion of Oxycondone, Noroxycodone, Hydroxymorphine,Normethoxymorphone in Urine(Single Dose)	Pre-dose,post dose0-2h,post dose2-4h,post dose4-8h,post dose8-12h,post dose12-24h	The excretion of drugs were calculated according to the concentration and volume of drugs in urine after single dose.
Vd for Participants Who Received a Single Dose	blood sample at predose,15min,30min,45min,1,1.5,2,3,4,6,8,12,24hr post-dose.	To calculate Apparent Distribution Volume (Vd) Vd of Oxycondone,Noroxycodone,Hydroxymorphine, Normethoxymorphone with Non-atrioventricular model method in single dose 5mg,10mg,20mg.
ke for Participants Who Received a Single Dose	blood sample at predose,15min,30min,45min,1,1.5,2,3,4,6,8,12,24hr post-dose.	To calculate Terminal Elimination Rate (ke) of Oxycondone,Noroxycodone,Hydroxymorphine, Normethoxymorphone with Non-atrioventricular model method in single dose 5mg,10mg,20mg.
Tmax,t1/2 for Participants Who Received Multiple Dose	Predose for the 1st, 2nd, 3rd day and predose,15min,30min,45min,1,1.5,2,3,4,6,8,12,24 post dose on the 4th day.	To calculate Tmax,t1/2 of Oxycondone,Noroxycodone,Hydroxymorphine, Normethoxymorphone with Non-atrioventricular model method in multiple dose 10mg.
Clearance Rate for Participants Who Received a Single Dose	blood sample at predose,15min,30min,45min,1,1.5,2,3,4,6,8,12,24hr post-dose.	To calculate CL of Oxycondone,Noroxycodone,Hydroxymorphine, Normethoxymorphone with Non-atrioventricular model method in single dose 5mg,10mg,20mg.
Fluctuation Index (DF) for Participants Who Received Multiple Dose	Predose for the 1st, 2nd, 3rd day and predose,15min,30min,45min,1,1.5,2,3,4,6,8,12,24 post dose on the 4th day.	To calculate Fluctuation index (DF) of Drug Valley and Peak Concentration of Oxycondone,Noroxycodone,Hydroxymorphine, Normethoxymorphone with Non-atrioventricular model method in multiple dose 10mg.
Tmax,t1/2 for Participants Who Received a Single Dose	blood sample at predose,15min,30min,45min,1,1.5,2,3,4,6,8,12,24hr post-dose.	To calculate Tmax,t1/2 of Oxycondone,Noroxycodone,Hydroxymorphine, Normethoxymorphone with Non-atrioventricular model method in single dose 5mg,10mg,20mg.
Css_min,Css_max and Css_av for Participants Who Received Multiple Dose	Predose for the 1st, 2nd, 3rd day and predose,15min,30min,45min,1,1.5,2,3,4,6,8,12,24 post dose on the 4th day.	To calculate Css_min,Css_max and Css_av of Oxycondone,Noroxycodone,Hydroxymorphine, Normethoxymorphone with Non-atrioventricular model method in multiple dose 10mg.
Cumulative Excretion of Oxycondone, Noroxycodone, Hydroxymorphine,Normethoxymorphone in Urine(Single Dose)	post dose0-2h,post dose2-4h,post dose4-8h,post dose8-12h,post dose12-24h	Cumulative excretion of drugs were calculated according to the concentration and volume of drugs in urine after single dose.
Cumulative Excretion of Oxycondone, Noroxycodone, Hydroxymorphine,Normethoxymorphone in Urine(Mutilple Dose)	post dose0-2h,post dose2-4h,post dose4-8h,post dose8-12h,post dose12-24h on the 4th day	Cumulative excretion of drugs were calculated according to the concentration and volume of drugs in urine after multiple dose on the 4th day .
Average Cumulative Excretion Rate of Oxycondone, Noroxycodone, Hydroxymorphine,Normethoxymorphone in Urine(Single Dose)	post dose 24h	Average cumulative excretion rate of drugs were calculated according to the concentration and volume of drugs in urine after single dose.
The Excretion of Oxycondone, Noroxycodone, Hydroxymorphine,Normethoxymorphone in Urine(Multiple Dose)	Pre-dose,post dose0-2h,post dose2-4h,post dose4-8h,post dose8-12h,post dose12-24h on the 4th day	The excretion of drugs were calculated according to the concentration and volume of drugs in urine after multiple dose on the 4th day.