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

Study Overview
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Brief Summary
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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
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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.

Official Title
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OxyNorm® Capsules (Immediate-Release) PK Study

Conditions
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Pain

Intervention / Treatment
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* Drug: Oxycodone hydrochloride


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 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: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxycodone Hydrochloride 5 mg Capsules<br>Group 1: single dose Oxycodone Hydrochloride 5 mg Capsules after 10 hours fasting | Drug: Oxycodone hydrochloride<br>* The subjects will be randomized to receive either a single dose of OxyNorm® Capsules 5, 10, 20mg, or multiple-dose OxyNorm® Capsules 10 mg for 13 times.<br>* Other names: OxyNorm® Capsules;|
| Experimental: Oxycodone Hydrochloride 10 mg Capsules<br>Group 2: single dose Oxycodone Hydrochloride 10 mg Capsules after 10 hours fasting | Drug: Oxycodone hydrochloride<br>* The subjects will be randomized to receive either a single dose of OxyNorm® Capsules 5, 10, 20mg, or multiple-dose OxyNorm® Capsules 10 mg for 13 times.<br>* Other names: OxyNorm® Capsules;|
| Experimental: Oxycodone Hydrochloride 20 mg Capsules<br>Group 3: single dose Oxycodone Hydrochloride 20 mg Capsules after 10 hours fasting | Drug: Oxycodone hydrochloride<br>* The subjects will be randomized to receive either a single dose of OxyNorm® Capsules 5, 10, 20mg, or multiple-dose OxyNorm® Capsules 10 mg for 13 times.<br>* Other names: OxyNorm® Capsules;|
| Experimental: Oxycodone Hydrochloride 10 mg Capsules(multi-dose)<br>Group 4: multi-dose 4 times per day Oxycodone Hydrochloride 10mg Capsules for 3 days, and one dose on 4th day morning | Drug: Oxycodone hydrochloride<br>* The subjects will be randomized to receive either a single dose of OxyNorm® Capsules 5, 10, 20mg, or multiple-dose OxyNorm® Capsules 10 mg for 13 times.<br>* Other names: OxyNorm® Capsules;|

What is the study measuring?
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Primary Outcome Measures

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