PROBE: PROspective Non-interventional Open laBEl Trial for TARGIN in Korean Patients With Cancer Pain

• Sponsor: Mundipharma Korea Ltd (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01719757
• Collaborator: (none)
• Enrollment: 359
• Location: 1
• Arm: 1
• Duration (Months): 21
• Patients Per Site Per Month: 17.1

Study Details

Study Description

Brief Summary

The aim of the study is to evaluate the efficacy of TARGIN administration as an analgesic to Korean patients treated with opioid analgesics for moderate-to-severe cancer pain under conditions of daily practice.

Condition or Disease	Intervention/Treatment	Phase
Cancer	Drug: Oxycodone/Naloxone	Phase 4

Detailed Description

An open-label, multi-center, nonrandomized, prospective, non-interventional, observational phase IV trial.

At the first visit, a detailed medical history is taken, including previous analgesics and concomitant treatment. After inclusion, patients enter a 4-week observation period during which they will receive bid of TARGIN 10/5mg and/or 20/10mg. The dose adjustments of TARGIN as well as of analgesic co-medication, rescue-medication and other treatments (e.g. laxatives) can be performed at any time-point during the observation period by the physician in dependence of medical demand. The asymmetric dose is allowed during the observation period by the physician's judgment. (e.g. 10/5 mg in the morning and 20/10 mg in the evening).

Data are gathered using interview-administered questionnaires at baseline (visit 1) and study end (visit 2).

During the observation period, unscheduled visits are allowed after the first visit due to inadequate pain control or occurrence of adverse events.

Study Design

• Study Type: Interventional
• Actual Enrollment: 359 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 4-week, Open Label, Multi-center, Prospective, Single-arm, Non-interventional Phase IV Study to Evaluate the Efficacy of Targin for the Treatment of Korean Patients With Cancer Pain Under Conditions of Daily Practice
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oxycodone/naloxone Trade name is Targin. Oxycodone (10mg)/naloxone (5mg) or Oxycodone (20mg)/naloxone (10mg) tablets. Twice daily per oral. Dose adjustment and asymmetric dose are allowed up to 80/40mg per day	Drug: Oxycodone/Naloxone; Twice daily; Other Names: Targin

Outcome Measures

Primary Outcome Measures

1. Change in Numeric Rating Scales (NRS) Score [4 weeks]

   Primary objective: Change in numeric rating scales (NRS) such as score for average pain levels over the previous 24 hours, from baseline (visit 1) to study end (visit 2). NRS score was measured from 0 (No pain) to 10(worst pain imaginable).

Secondary Outcome Measures

1. Change of Eastern Cooperative Oncology Group(ECOG) Performance Status [4weeks]

   If ECOG P.S score is increased from baseline to visit2, the results mean that QOL was worse. ECOG P.S grade: 0=Fully active, able to carry on all pre-disease performance without restriction, 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work,2=Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours,3=Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours,4=Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair,5=Death.

2. Change of Constipation Assessment From Baseline to Visit 2(End Visit) [4 weeks]

   Constipation assessment(5-point scale; 0=none, 1=mild, 2=moderate, 3=severe, 4=very severe, for the patient's judgment of the intensity of symptoms)

3. Overall Satisfaction Assessment About Efficacy and Tolerability of Oxycodone/Naloxone by the Investigator and Subject [4 weeks]

   The overall satisfactions by investigators & subjects were assessed 5 steps such as Very good, Good, Satisfactory, Bad, Very bad.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female cancer patients 20 years of age or older

2. Cancer related pain that requires treatment with continuous around-the-clock strong opioid analgesic

3. Moderate to severe pain intensity (NRS pain score >=4)

4. Opioid naïve patients or patients not treated with strong opioids (Only except occasional PRN) within 13 months or patients who has been on weak opioids

5. Ability to communicate effectively with the study personnel regarding pain intensity, constipation assessment, final assessment of overall efficacy and tolerability

6. Subject who provide signed and dated written voluntary informed consent

Exclusion Criteria:

1. Pregnant or nursing (lactating) women

2. Have previously received treatment with Targin

3. Patient with evidence of significant structural/functional abnormalities of GI tract which is not appropriate for oral medicine administration

4. Any history of hypersensitivity to Oxycodone and Naloxone or any excipients

5. Patients with significant respiratory depression

6. Patients with acute or severe bronchial asthma or hypercarbia

7. Any patient who has or is suspected of having paralytic ileus

8. Severe Chronic obstructive pulmonary disease, pulmonary heart disease

9. Targin product contains lactose. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take

10. Patients with moderate and severe hepatic impairment

11. Abnormal aspartate aminotransferase (AST; SGOT), alanine aminotransferase (ALT; SGPT), or alkaline phosphatase levels (>2.5 times the upper limit of normal, it is allowed >5 times the upper limit of normal in case of transition in liver) or an abnormal total bilirubin and/or creatinine level(s) (greater than 1.5 times the upper limit of normal)

12. Any situation where opioids are contraindicated

13. With a life expectancy < 1 month

14. Any situation where opioids are contraindicated

15. Mainly pain originated other than cancer or cancer related conditions (eg. Musculoskeletal pain, inflammatory pain, diabetic polyneuropathy)

16. Patients with known or suspected unstable brain metastases or spinal cord compression that may require changes in steroid treatment throughout the duration of the study

17. Patients with uncontrolled seizures

18. Requiring interventional treatment for pain such as neurodestructive procedure or regional infusion

19. With a history of alcohol abuse within 6 months of screening

20. With a history of illicit drug abuse within 6 months of screening

21. Patients with increased intracranial pressure

22. Having used other investigational drugs at the time of enrollment, or within 30 days.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	13 sites including Yeungnam University Medical Center	Daegu		Korea, Republic of	705-717

Sponsors and Collaborators

• Mundipharma Korea Ltd

Investigators

• Principal Investigator: Kyeonghee Lee, PhD, Yeongnam Univ. hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mundipharma Korea Ltd
• ClinicalTrials.gov Identifier: NCT01719757
• Other Study ID Numbers: OXN11-KR-404
• First Posted: Nov 1, 2012
• Last Update Posted: Aug 19, 2016
• Last Verified: Jul 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Mundipharma Korea Ltd: Targin, Cancer Pain
• Additional relevant MeSH terms: Cancer Pain; Oxycodone; Naloxone

Study Results

Participant Flow

Recruitment Details	Safety set: 359 ITT set: 304

Arm/Group Title	Oxycodone/Naloxone
Arm/Group Description	Trade name is Targin. Oxycodone (10mg)/naloxone (5mg) or Oxycodone (20mg)/naloxone (10mg) tablets. Twice daily per oral. Dose adjustment and asymmetric dose are allowed up to 80/40mg per day Oxycodone/Naloxone: Twice daily
Period Title: Overall Study
STARTED	359
COMPLETED	258
NOT COMPLETED	101

Baseline Characteristics

Arm/Group Title	Oxycodone/Naloxone
Arm/Group Description	Trade name is Targin. Oxycodone (10mg)/naloxone (5mg) or Oxycodone (20mg)/naloxone (10mg) tablets. Twice daily per oral. Dose adjustment and asymmetric dose are allowed up to 80/40mg per day Oxycodone/Naloxone: Twice daily
Overall Participants	359
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	179 49.9%
>=65 years	180 50.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.73 (11.07)
Sex: Female, Male (Count of Participants)
Female	134 37.3%
Male	225 62.7%
Region of Enrollment (participants) [Number]
Korea, Republic of	359 100%

Outcome Measures

1. Primary Outcome

Title	Change in Numeric Rating Scales (NRS) Score
Description	Primary objective: Change in numeric rating scales (NRS) such as score for average pain levels over the previous 24 hours, from baseline (visit 1) to study end (visit 2). NRS score was measured from 0 (No pain) to 10(worst pain imaginable).
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat analysis set: 304

Arm/Group Title	Oxycodone/Naloxone
Arm/Group Description	Trade name is Targin. Oxycodone (10mg)/naloxone (5mg) or Oxycodone (20mg)/naloxone (10mg) tablets. Twice daily per oral. Dose adjustment and asymmetric dose are allowed up to 80/40mg per day Oxycodone/Naloxone: Twice daily
Measure Participants	304
Mean (Standard Deviation) [units on a scale]	-1.89 (2.16)

2. Secondary Outcome

Title	Change of Eastern Cooperative Oncology Group(ECOG) Performance Status
Description	If ECOG P.S score is increased from baseline to visit2, the results mean that QOL was worse. ECOG P.S grade: 0=Fully active, able to carry on all pre-disease performance without restriction, 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work,2=Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours,3=Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours,4=Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair,5=Death.
Time Frame	4weeks

Outcome Measure Data

Analysis Population Description

Intent to treat analysis set: 304

Arm/Group Title	Oxycodone/Naloxone
Arm/Group Description	Trade name is Targin. Oxycodone (10mg)/naloxone (5mg) or Oxycodone (20mg)/naloxone (10mg) tablets. Twice daily per oral. Dose adjustment and asymmetric dose are allowed up to 80/40mg per day Oxycodone/Naloxone: Twice daily
Measure Participants	304
Mean (Standard Deviation) [Score]	0.08 (0.52)

3. Secondary Outcome

Title	Change of Constipation Assessment From Baseline to Visit 2(End Visit)
Description	Constipation assessment(5-point scale; 0=none, 1=mild, 2=moderate, 3=severe, 4=very severe, for the patient's judgment of the intensity of symptoms)
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat analysis set(Last observational carried forward)

Arm/Group Title	Oxycodone/Naloxone
Arm/Group Description	Trade name is Targin. Oxycodone (10mg)/naloxone (5mg) or Oxycodone (20mg)/naloxone (10mg) tablets. Twice daily per oral. Dose adjustment and asymmetric dose are allowed up to 80/40mg per day Oxycodone/Naloxone: Twice daily
Measure Participants	304
Mean (Standard Deviation) [score]	-0.03 (0.67)

4. Secondary Outcome

Title	Overall Satisfaction Assessment About Efficacy and Tolerability of Oxycodone/Naloxone by the Investigator and Subject
Description	The overall satisfactions by investigators & subjects were assessed 5 steps such as Very good, Good, Satisfactory, Bad, Very bad.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat analysis set(Last observational carried forward)

Arm/Group Title	Investigator	Subject
Arm/Group Description	For overall satisfaction assessement of oxycodone/naloxone by investigator	For overall satisfaction assessement of oxycodone/naloxone by subject
Measure Participants	304	304
Very good	24 6.7%	12 NaN
Good	80 22.3%	78 NaN
Satisfactory	146 40.7%	156 NaN
Bad	53 14.8%	55 NaN
Very Bad	1 0.3%	3 NaN

Adverse Events

Time Frame	Safety data were analyzed based on AEs and compliance in the safety set that included subjects who had at least one dose of the study drug and were assessed for safety. Patients were followed safety profile by 4weeks.
Arm/Group Title	Oxycodone/Naloxone
Arm/Group Description	Trade name is Targin. Oxycodone (10mg)/naloxone (5mg) or Oxycodone (20mg)/naloxone (10mg) tablets. Twice daily per oral. Dose adjustment and asymmetric dose are allowed up to 80/40mg per day Oxycodone/Naloxone: Twice daily
All Cause Mortality
	Oxycodone/Naloxone
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Oxycodone/Naloxone
	Affected / at Risk (%)	# Events
Total	51/359 (14.2%)
Blood and lymphatic system disorders
Anaemia	2/359 (0.6%)	2
Febrile neutropenia	2/359 (0.6%)	2
Pancytopenia	1/359 (0.3%)	1
Ear and labyrinth disorders
Vertigo positional	1/359 (0.3%)	1
Gastrointestinal disorders
Nausea	3/359 (0.8%)	3
Diarrhoea	2/359 (0.6%)	2
Abdominal pain	5/359 (1.4%)	5
Abdominal distension	1/359 (0.3%)	1
Haematochezia	1/359 (0.3%)	1
Ascites	1/359 (0.3%)	1
Gastrointestinal hypomotility	1/359 (0.3%)	1
Ileus	1/359 (0.3%)	1
Melaena	1/359 (0.3%)	1
General disorders
Pyrexia	3/359 (0.8%)	3
Asthenia	6/359 (1.7%)	6
Fatigue	1/359 (0.3%)	1
Disease progression	4/359 (1.1%)	4
Chest discomfort	1/359 (0.3%)	1
Pain	1/359 (0.3%)	1
Infections and infestations
Pneumonia	3/359 (0.8%)	3
Urinary tract infection	1/359 (0.3%)	1
Pulmonary tuberculosis	1/359 (0.3%)	1
Sepsis	1/359 (0.3%)	1
Wound infection	1/359 (0.3%)	1
Injury, poisoning and procedural complications
Radiation pneumonitis	1/359 (0.3%)	1
Radiation skin injury	1/359 (0.3%)	1
Spinal compression fracture	1/359 (0.3%)	1
Investigations
Weight decreased	1/359 (0.3%)	1
Metabolism and nutrition disorders
Glucose tolerance impaired	1/359 (0.3%)	1
Hypercalcaemia	1/359 (0.3%)	1
Musculoskeletal and connective tissue disorders
Pain in extremity	1/359 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	1/359 (0.3%)	1
Psychiatric disorders
Delirium	1/359 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/359 (0.6%)	2
Haemoptysis	1/359 (0.3%)	1
Pneumonitis	1/359 (0.3%)	1
Pleural effusion	1/359 (0.3%)	1
Vascular disorders
Embolism	1/359 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Oxycodone/Naloxone
	Affected / at Risk (%)	# Events
Total	227/359 (63.2%)
Blood and lymphatic system disorders
Anaemia	8/359 (2.2%)	9
Febrile neutropenia	5/359 (1.4%)	5
Neutropenia	5/359 (1.4%)	5
Pancytopenia	1/359 (0.3%)	1
Ear and labyrinth disorders
Vertigo positional	1/359 (0.3%)	1
Gastrointestinal disorders
Constipation	59/359 (16.4%)	61
Nausea	48/359 (13.4%)	52
Vomiting	25/359 (7%)	28
Diarrhoea	22/359 (6.1%)	29
Abdominal pain	14/359 (3.9%)	15
Dyspepsia	9/359 (2.5%)	10
Stomatitis	9/359 (2.5%)	9
Abdominal discomfort	5/359 (1.4%)	5
Abdominal distension	5/359 (1.4%)	5
Abdominal pain upper	4/359 (1.1%)	4
Dysphagia	4/359 (1.1%)	4
Epigastric discomfort	2/359 (0.6%)	2
Haematochezia	2/359 (0.6%)	2
Ascites	1/359 (0.3%)	1
Gastrointestinal hypomotility	1/359 (0.3%)	1
Gastrointestinal pain	1/359 (0.3%)	1
Ileus	1/359 (0.3%)	1
Melaena	1/359 (0.3%)	1
Mouth ulceration	1/359 (0.3%)	1
Oral pain	1/359 (0.3%)	1
Rectal haemorrhage	1/359 (0.3%)	1
Tongue ulceration	1/359 (0.3%)	1
General disorders
Pyrexia	24/359 (6.7%)	33
Asthenia	20/359 (5.6%)	23
Fatigue	7/359 (1.9%)	7
Chills	6/359 (1.7%)	7
Disease progression	6/359 (1.7%)	6
Chest discomfort	4/359 (1.1%)	4
Oedema	4/359 (1.1%)	5
Pain	4/359 (1.1%)	4
Oedema peripheral	3/359 (0.8%)	3
Catheter site oedema	1/359 (0.3%)	1
Face oedema	1/359 (0.3%)	1
Generalised oedema	1/359 (0.3%)	1
Non-cardiac chest pain	1/359 (0.3%)	1
Hepatobiliary disorders
Hyperbilirubinaemia	1/359 (0.3%)	1
Immune system disorders
Hypersensitivity	1/359 (0.3%)	1
Infections and infestations
Upper respiratory tract infection	4/359 (1.1%)	4
Oral candidiasis	3/359 (0.8%)	3
Pneumonia	3/359 (0.8%)	3
Furuncle	2/359 (0.6%)	2
Herpes zoster	2/359 (0.6%)	2
Urinary tract infection	2/359 (0.6%)	2
Localised infection	1/359 (0.3%)	1
Pulmonary tuberculosis	1/359 (0.3%)	1
Sepsis	1/359 (0.3%)	1
Tuberculosis	1/359 (0.3%)	1
Wound infection	1/359 (0.3%)	1
Injury, poisoning and procedural complications
Face injury	1/359 (0.3%)	1
Laceration	1/359 (0.3%)	1
Post procedural complication	1/359 (0.3%)	1
Radiation pneumonitis	1/359 (0.3%)	1
Radiation skin injury	1/359 (0.3%)	1
Spinal compression fracture	1/359 (0.3%)	1
Investigations
Alanine aminotransferase increased	2/359 (0.6%)	2
Aspartate aminotransferase increased	2/359 (0.6%)	2
Neutrophil count decreased	2/359 (0.6%)	3
Blood iron decreased	1/359 (0.3%)	1
Platelet count decreased	1/359 (0.3%)	1
Weight decreased	1/359 (0.3%)	1
Weight increased	1/359 (0.3%)	1
Metabolism and nutrition disorders
Decreased appetite	36/359 (10%)	41
Hyperglycaemia	2/359 (0.6%)	3
Hyperkalaemia	2/359 (0.6%)	2
Hypocalcaemia	2/359 (0.6%)	2
Hypokalaemia	2/359 (0.6%)	3
Hypomagnesaemia	2/359 (0.6%)	2
Glucose tolerance impaired	1/359 (0.3%)	1
Hypercalcaemia	1/359 (0.3%)	1
Hypoglycaemia	1/359 (0.3%)	1
Musculoskeletal and connective tissue disorders
Back pain	7/359 (1.9%)	7
Pain in extremity	4/359 (1.1%)	6
Myalgia	2/359 (0.6%)	2
Neck pain	2/359 (0.6%)	2
Bone pain	1/359 (0.3%)	1
Flank pain	1/359 (0.3%)	1
Muscular weakness	1/359 (0.3%)	1
Musculoskeletal pain	1/359 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	1/359 (0.3%)	1
Nervous system disorders
Dizziness	15/359 (4.2%)	15
Headache	8/359 (2.2%)	8
Hypersomnia	2/359 (0.6%)	2
Somnolence	2/359 (0.6%)	2
Speech disorder	2/359 (0.6%)	2
Amnesia	1/359 (0.3%)	1
Cognitive disorder	1/359 (0.3%)	1
Hypoaesthesia	1/359 (0.3%)	1
Muscle spasticity	1/359 (0.3%)	1
Neuralgia	1/359 (0.3%)	1
Neuropathy peripheral	1/359 (0.3%)	2
Psychiatric disorders
Insomnia	5/359 (1.4%)	7
Anxiety	1/359 (0.3%)	1
Confusional state	1/359 (0.3%)	1
Delirium	1/359 (0.3%)	1
Renal and urinary disorders
Dysuria	6/359 (1.7%)	6
Bladder dilatation	1/359 (0.3%)	1
Haematuria	1/359 (0.3%)	1
Pollakiuria	1/359 (0.3%)	1
Urinary tract disorder	1/359 (0.3%)	1
Urinary tract obstruction	1/359 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	8/359 (2.2%)	8
Dyspnoea	7/359 (1.9%)	7
Hiccups	6/359 (1.7%)	6
Productive cough	6/359 (1.7%)	6
Oropharyngeal pain	3/359 (0.8%)	3
Haemoptysis	2/359 (0.6%)	2
Pneumonitis	2/359 (0.6%)	2
Pleural effusion	1/359 (0.3%)	1
Rhinorrhoea	1/359 (0.3%)	1
Skin and subcutaneous tissue disorders
Pruritus	4/359 (1.1%)	4
Cold sweat	2/359 (0.6%)	2
Rash	2/359 (0.6%)	2
Alopecia	1/359 (0.3%)	1
Nail disorder	1/359 (0.3%)	1
Rash macular	1/359 (0.3%)	1
Skin disorder	1/359 (0.3%)	1
Skin exfoliation	1/359 (0.3%)	1
Swelling face	1/359 (0.3%)	1
Urticaria	1/359 (0.3%)	1
Vascular disorders
Flushing	4/359 (1.1%)	4
Hypertension	4/359 (1.1%)	4
Embolism	1/359 (0.3%)	1
Hypotension	1/359 (0.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.