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A Study to Compare the Titration Efficacy and Safety of Control-released Oxycodone and Immediate-released Oxycodone in Patients With Moderate to Severe Cancer Pain

Primary Purpose

Cancer, Pain

Status
Completed
Phase
Phase 4
Locations
Taiwan
Study Type
Interventional
Intervention
Oxycodone
Oxycodone
Sponsored by
Taiwan Mundipharma Pharmaceuticals Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cancer focused on measuring control-released oxycodone, immediate-released oxycodone, cancer pain, opioid-naive

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Cancer patients aged 20 years old and over
  2. Patients with background cancer pain more than or equal to NRS 4 during previous 24 hours, or receive more than or equal to 3 times/day for breakthrough pain medication management
  3. ECOG ≤ 2
  4. Opioid-naive patients who are not administrated any strong opioid for at least one month prior to the index treatments, who currently with poor pain control and intended to be treated for pain relief with strong opioids. The FDA identifies opioid-naive as who not receiving the following treatment for a week or longer of strong opioids:

1) ≥ 60 mg of morphine daily 2) ≥25 mcg transdermalfentanyl/hour 3) ≥ 8 mg of oral hydromorphone daily or 4) an equianalgesic dose of another opioid

5) Patients who will not be treated with radiotherapy within 7 days prior to randomization and during study

6) Patients who need chemotherapy, long term administration of hormone, targeted therapy, or bisphosphonates therapy should undergo a stable anti-tumor therapy prior to randomization.

7) Patients or his/her caregivers who are able to fill out the diary and questionnaire forms

Exclusion Criteria:

  1. Patients diagnosed with non-cancer pain or unexplained pain
  2. Patients suffered with post-op pain
  3. Patients who cannot be applicable for oral administration
  4. Patients who have severe constipation defined by CTCAE grade 3 and above
  5. Patients with any disease that may easily lead to respiratory depression
  6. Monoamine oxidase inhibitor (MAOI) was administrated one week before randomization
  7. There are abnormal lab results, with obvious clinical significance, such as the creatinine ≥ 2 fold of upper limit of normal value, or ALT or AST ≥ 2.5 fold of upper limit of normal value (≥ 5 fold, to the patients with liver metastasis or primary liver cancer), or liver function of Child C grade
  8. Patients who have potential risk for surgical operation, which may lead to gastrointestinal stenosis, blind loop or gastrointestinal obstruction; or patient is unable to effectively absorb oral medication through gastrointestinal tract
  9. Patients who are drug or alcohol abuse
  10. Patients with moderate to severe psychiatric problems
  11. Patients who have hypersensitivity to oxycodone
  12. Patients who are pregnant or lactating
  13. Patients who are clinically unstable or have a life expectancy of less than three months making completion of the trial unlikely

Sites / Locations

  • Changhua Christian Hospital
  • Taichung Veterans General Hospital
  • National Taiwan University Hospital
  • Taipei Veterans General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Control-released oxycodone

Immediate-released oxycodone

Arm Description

Control-released oxycodone Q12H, initial daily dose is 20 mg + immediate-released oxycodone for PRN

Immediate-released oxycodone Q6H, initial daily dose is 20mg + immediate-released oxycodone for PRN

Outcomes

Primary Outcome Measures

To evaluate the variable change of NRS pain score and the number of breakthrough pain to obtain pain control after treatment
The change from baseline of NRS pain score and the daily number of breakthrough pain

Secondary Outcome Measures

To evaluate the percentage of patients in each titration cycle
The percentage of patients in each titration cycle
To evaluate the number of patients who switched/discontinued therapy due to serious adverse events or lack of pain control
The number of patients who switched/discontinued therapy due to serious adverse events or lack of pain control
The total opioid taken within 24hrs daily from baseline to day 14
The total opioid taken within 24 hrs daily from baseline to day 14
To evaluate the mean daily NRS score of subjects from baseline to day 14
Mean daily NRS score of patients from baseline to day 14
To evaluate the total daily rescue dose taken (immediate-released oxycodone capsule) for treatment of breakthrough pain among patients from baseline to day 14
The total daily rescue dose taken (immediate-released oxycodone capsule) for treatment of breakthrough pain among patients from baseline to day 14
To evaluate the tolerability and safety of Oxycodone CR and IR in cancer pain patient
The occurrence rate of adverse events and physical examination status
To evaluate the change from baseline in questionnaire
The change from baseline in questionnaire

Full Information

First Posted
June 1, 2017
Last Updated
March 16, 2020
Sponsor
Taiwan Mundipharma Pharmaceuticals Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT03176199
Brief Title
A Study to Compare the Titration Efficacy and Safety of Control-released Oxycodone and Immediate-released Oxycodone in Patients With Moderate to Severe Cancer Pain
Official Title
An Interventional, Open Label, and Randomized Controlled Study to Compare the Titration Efficacy and Safety of Control-released Oxycodone and Immediate-released Oxycodone in Opioid-naive Patients With Moderate to Severe Cancer Pain
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
September 1, 2016 (Actual)
Primary Completion Date
December 31, 2018 (Actual)
Study Completion Date
December 31, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Taiwan Mundipharma Pharmaceuticals Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study is to evaluate the efficacy and safety of a titration method by selects 10 mg control-released (CR) oxycodone tablet as background drug in combined with immediate-released (IR) oxycodone, compared to conventional titration method with immediate-released (IR) oxycodone in patients with moderate to severe cancer pain in Taiwan.
Detailed Description
This is an interventional, open label, randomized controlled study carrying in multi-centers. Eighty opioid-naive patients with moderate to severe cancer pain (≥ 4) in outpatient department (OPD), who agreed and signed informed consent will be randomly assigned in a 1:1 ratio to receive CR + IR oxycodone or conventional IR oxycodone groups. The study is to compare the titration efficacy and safety of CR with IR oxycodone (experimental group) comparing IR oxycodone (control group) in cancer patients suffered with moderate to severe pain. The study last 14 days. Patients begin the study by the first day visit of the clinic and received the study medication (Baseline). Following visits on cycle 1 (day 3 or 4 depends on the available clinics), cycle 2 (day 7±1), cycle 3 (day 10±1), and cycle 4 (day 14±1). In the experimental group, 10 mg CR oxycodone tablet will be selected as background dose of titration, and patients will be administered once every 12 hrs. Meanwhile, the titration with IR oxycodone will be added according to the pain intensity, e.g. if patient receiving 6 tablets of 10 mg CR oxycodone (giving in Q12H frequency for 3 days), 12 capsules of 5mg IR oxycodone will be dispensed for managing acute pain (rescue use) for the first cycle. In the control group, the conventional titration with IR oxycodone will be conducted according to pain intensity, using 5 mg as initial dose, e.g. 12 capsules of 5mg IR oxycodone (giving in Q6H frequency for 3 days), 12 capsules of 5mg IR oxycodone will be dispensed for rescue use upon to the first cycle. Patient will record their pain score (4 times in Q6H frequency and before taking the drug), 24hr total dose (total tablets/capsule number), number of breakthrough pain and PRN time and dosage used onto the patient diary. The background dose of each patient will be titrated after cycle 1 by investigators. Titration cycles will be recorded and evaluated pain assessments on cycle 2 (day 7±1), cycle 3 (Day 10±1), cycle 4 (day 14±1). During study, the study nurse will follow patient's daily records, drug use condition every second day by telephone or other contact methods to keep close monitor of patient's condition. The telephone contact for cycle 1 and cycle 3 is acceptable for this study. If the telephone contact is conducted for patient, the 1-week quantities of oxycodone should be dispensed to patient. The safety for individual patient will be followed during study up to end of treatment (EOT) or early termination (ET). All adverse events (AE(s)) and serious adverse events (SAE(s)) occurred during the study period will be followed until resolution or the event is considered stable.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer, Pain
Keywords
control-released oxycodone, immediate-released oxycodone, cancer pain, opioid-naive

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Control-released oxycodone
Arm Type
Experimental
Arm Description
Control-released oxycodone Q12H, initial daily dose is 20 mg + immediate-released oxycodone for PRN
Arm Title
Immediate-released oxycodone
Arm Type
Active Comparator
Arm Description
Immediate-released oxycodone Q6H, initial daily dose is 20mg + immediate-released oxycodone for PRN
Intervention Type
Drug
Intervention Name(s)
Oxycodone
Intervention Description
Every 12 hours for control-released oxycodone (OxyContin®)
Intervention Type
Drug
Intervention Name(s)
Oxycodone
Intervention Description
Every 6 hours for immediate-released oxycodone (OxyNorm®)
Primary Outcome Measure Information:
Title
To evaluate the variable change of NRS pain score and the number of breakthrough pain to obtain pain control after treatment
Description
The change from baseline of NRS pain score and the daily number of breakthrough pain
Time Frame
Up to 14 days
Secondary Outcome Measure Information:
Title
To evaluate the percentage of patients in each titration cycle
Description
The percentage of patients in each titration cycle
Time Frame
Up to 14 days
Title
To evaluate the number of patients who switched/discontinued therapy due to serious adverse events or lack of pain control
Description
The number of patients who switched/discontinued therapy due to serious adverse events or lack of pain control
Time Frame
Up to 14 days
Title
The total opioid taken within 24hrs daily from baseline to day 14
Description
The total opioid taken within 24 hrs daily from baseline to day 14
Time Frame
Up to 14 days
Title
To evaluate the mean daily NRS score of subjects from baseline to day 14
Description
Mean daily NRS score of patients from baseline to day 14
Time Frame
Up to 14 days
Title
To evaluate the total daily rescue dose taken (immediate-released oxycodone capsule) for treatment of breakthrough pain among patients from baseline to day 14
Description
The total daily rescue dose taken (immediate-released oxycodone capsule) for treatment of breakthrough pain among patients from baseline to day 14
Time Frame
Up to 14 days
Title
To evaluate the tolerability and safety of Oxycodone CR and IR in cancer pain patient
Description
The occurrence rate of adverse events and physical examination status
Time Frame
Up to 28 days
Title
To evaluate the change from baseline in questionnaire
Description
The change from baseline in questionnaire
Time Frame
Up to 14 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Cancer patients aged 20 years old and over Patients with background cancer pain more than or equal to NRS 4 during previous 24 hours, or receive more than or equal to 3 times/day for breakthrough pain medication management ECOG ≤ 2 Opioid-naive patients who are not administrated any strong opioid for at least one month prior to the index treatments, who currently with poor pain control and intended to be treated for pain relief with strong opioids. The FDA identifies opioid-naive as who not receiving the following treatment for a week or longer of strong opioids: 1) ≥ 60 mg of morphine daily 2) ≥25 mcg transdermalfentanyl/hour 3) ≥ 8 mg of oral hydromorphone daily or 4) an equianalgesic dose of another opioid 5) Patients who will not be treated with radiotherapy within 7 days prior to randomization and during study 6) Patients who need chemotherapy, long term administration of hormone, targeted therapy, or bisphosphonates therapy should undergo a stable anti-tumor therapy prior to randomization. 7) Patients or his/her caregivers who are able to fill out the diary and questionnaire forms Exclusion Criteria: Patients diagnosed with non-cancer pain or unexplained pain Patients suffered with post-op pain Patients who cannot be applicable for oral administration Patients who have severe constipation defined by CTCAE grade 3 and above Patients with any disease that may easily lead to respiratory depression Monoamine oxidase inhibitor (MAOI) was administrated one week before randomization There are abnormal lab results, with obvious clinical significance, such as the creatinine ≥ 2 fold of upper limit of normal value, or ALT or AST ≥ 2.5 fold of upper limit of normal value (≥ 5 fold, to the patients with liver metastasis or primary liver cancer), or liver function of Child C grade Patients who have potential risk for surgical operation, which may lead to gastrointestinal stenosis, blind loop or gastrointestinal obstruction; or patient is unable to effectively absorb oral medication through gastrointestinal tract Patients who are drug or alcohol abuse Patients with moderate to severe psychiatric problems Patients who have hypersensitivity to oxycodone Patients who are pregnant or lactating Patients who are clinically unstable or have a life expectancy of less than three months making completion of the trial unlikely
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chih-Jen Hung, MSc
Organizational Affiliation
Taichung Veterans General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Changhua Christian Hospital
City
Chang-hua
ZIP/Postal Code
500
Country
Taiwan
Facility Name
Taichung Veterans General Hospital
City
Taichung
ZIP/Postal Code
40705
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Taipei Veterans General Hospital
City
Taipei
ZIP/Postal Code
11217
Country
Taiwan

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
16563318
Citation
Mercadante S, Porzio G, Ferrera P, Fulfaro F, Aielli F, Ficorella C, Verna L, Tirelli W, Villari P, Arcuri E. Low morphine doses in opioid-naive cancer patients with pain. J Pain Symptom Manage. 2006 Mar;31(3):242-7. doi: 10.1016/j.jpainsymman.2006.01.001.
Results Reference
background
PubMed Identifier
17331764
Citation
Mercadante S. Opioid titration in cancer pain: a critical review. Eur J Pain. 2007 Nov;11(8):823-30. doi: 10.1016/j.ejpain.2007.01.003. Epub 2007 Feb 28.
Results Reference
background
PubMed Identifier
12507714
Citation
Klepstad P, Kaasa S, Jystad A, Hval B, Borchgrevink PC. Immediate- or sustained-release morphine for dose finding during start of morphine to cancer patients: a randomized, double-blind trial. Pain. 2003 Jan;101(1-2):193-8. doi: 10.1016/s0304-3959(02)00328-7.
Results Reference
background
PubMed Identifier
22997447
Citation
Ripamonti CI, Santini D, Maranzano E, Berti M, Roila F; ESMO Guidelines Working Group. Management of cancer pain: ESMO Clinical Practice Guidelines. Ann Oncol. 2012 Oct;23 Suppl 7:vii139-54. doi: 10.1093/annonc/mds233. No abstract available.
Results Reference
background
PubMed Identifier
22300860
Citation
Caraceni A, Hanks G, Kaasa S, Bennett MI, Brunelli C, Cherny N, Dale O, De Conno F, Fallon M, Hanna M, Haugen DF, Juhl G, King S, Klepstad P, Laugsand EA, Maltoni M, Mercadante S, Nabal M, Pigni A, Radbruch L, Reid C, Sjogren P, Stone PC, Tassinari D, Zeppetella G; European Palliative Care Research Collaborative (EPCRC); European Association for Palliative Care (EAPC). Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. Lancet Oncol. 2012 Feb;13(2):e58-68. doi: 10.1016/S1470-2045(12)70040-2.
Results Reference
background
PubMed Identifier
17358098
Citation
Pan H, Zhang Z, Zhang Y, Xu N, Lu L, Dou C, Guo Y, Wu S, Yue J, Wu D, Dai Y. Efficacy and tolerability of oxycodone hydrochloride controlled-release tablets in moderate to severe cancer pain. Clin Drug Investig. 2007;27(4):259-67. doi: 10.2165/00044011-200727040-00005.
Results Reference
background
PubMed Identifier
10534967
Citation
Salzman RT, Roberts MS, Wild J, Fabian C, Reder RF, Goldenheim PD. Can a controlled-release oral dose form of oxycodone be used as readily as an immediate-release form for the purpose of titrating to stable pain control? J Pain Symptom Manage. 1999 Oct;18(4):271-9. doi: 10.1016/s0885-3924(99)00079-2.
Results Reference
background

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A Study to Compare the Titration Efficacy and Safety of Control-released Oxycodone and Immediate-released Oxycodone in Patients With Moderate to Severe Cancer Pain

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