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

• ClinicalTrials.gov Identifier: NCT01643772
• Recruitment Status: Completed
• First Posted: July 18, 2012
• Results First Posted: October 21, 2019
• Last Update Posted: October 21, 2019
• Sponsor: Mundipharma (China) Pharmaceutical Co. Ltd
• Information provided by (Responsible Party): Mundipharma (China) Pharmaceutical Co. Ltd

Tracking Information

• First Submitted Date: November 17, 2011
• First Posted Date: July 18, 2012
• Results First Submitted Date: January 5, 2018
• Results First Posted Date: October 21, 2019
• Last Update Posted Date: October 21, 2019
• Study Start Date: May 2011
• Actual Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 24, 2019)

• AUC0-t and AUC0-∞ for Participants Who Received a Single Dose [ Time Frame: 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.
• Cmax,Clast for Participants Who Received a Single Dose [ Time Frame: 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.
• Tmax,t1/2 for Participants Who Received a Single Dose [ Time Frame: 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.
• Clearance Rate for Participants Who Received a Single Dose [ Time Frame: 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.
• Vd for Participants Who Received a Single Dose [ Time Frame: 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 [ Time Frame: 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.
• AUCss for Participants Who Received Multiple Dose [ Time Frame: 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.
• Css_min,Css_max and Css_av for Participants Who Received Multiple Dose [ Time Frame: 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.
• Tmax,t1/2 for Participants Who Received Multiple Dose [ Time Frame: 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.
• CL for Participants Who Received Multiple Dose [ Time Frame: 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.
• Fluctuation Index (DF) for Participants Who Received Multiple Dose [ Time Frame: 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.
• The Excretion of Oxycondone, Noroxycodone, Hydroxymorphine,Normethoxymorphone in Urine(Single Dose) [ Time Frame: 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.
• Cumulative Excretion of Oxycondone, Noroxycodone, Hydroxymorphine,Normethoxymorphone in Urine(Single Dose) [ Time Frame: 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.
• Average Cumulative Excretion Rate of Oxycondone, Noroxycodone, Hydroxymorphine,Normethoxymorphone in Urine(Single Dose) [ Time Frame: 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) [ Time Frame: 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.
• Cumulative Excretion of Oxycondone, Noroxycodone, Hydroxymorphine,Normethoxymorphone in Urine(Mutilple Dose) [ Time Frame: 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 .

Original Primary Outcome Measures (submitted: July 17, 2012)

• Area under curve(AUC) [ Time Frame: predose,15min,30min,45min,1,1.5,2,3,4,6,8,12,24hr post-dose. ]
  To investigate the pharmacokinetic profile, dose-proportionality, and evaluate drug accumulation of Oxycodone Hydrochloride after single dose of OxyNorm® capsules.
• Area Under Curve(AUC) of time frame for Multi-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. [ Time Frame: 5 days ]
  To investigate the pharmacokinetic profile, dose-proportionality, and evaluate drug accumulation of Oxycodone Hydrochloride after multiple dose of OxyNorm® capsules.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: OxyNorm® Capsules (Immediate-Release) Pharmacokinetic (PK) Study
• Official Title: OxyNorm® Capsules (Immediate-Release) PK Study
• 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pain

Intervention

Drug: Oxycodone hydrochloride

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.

Other Name: OxyNorm® Capsules

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 24, 2013): 61
• Original Estimated Enrollment (submitted: July 17, 2012): 60
• Actual Study Completion Date: July 2012
• Actual Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT01643772
• Other Study ID Numbers: OXYC09-CN-102
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Mundipharma (China) Pharmaceutical Co. Ltd
• Original Responsible Party: Mundipharma Pte Ltd.
• Current Study Sponsor: Mundipharma (China) Pharmaceutical Co. Ltd
• Original Study Sponsor: Mundipharma Pte Ltd.
• Collaborators: Not Provided

Investigators

• Study Chair: Mundipharma China Ltd.; Mundipharma China Ltd.

• PRS Account: Mundipharma (China) Pharmaceutical Co. Ltd
• Verification Date: September 2019