Trial Outcomes & Findings for OXN PR Compared to OXY PR in Subjects With Postoperative Pain After Knee Arthroplasty (NCT NCT01083485)

Last Updated: 2012-02-16

Results Overview

The primary efficacy variable was the 24hr pain intensity score at rest, on a Numerical Rating Scale (NRS), with "0" = "no pain" and "10" = "worst possible pain". This was assessed 1 hour after dosing on Day 1 (evening only), Day 2(morning and evening) and Day 3 (morning only). The primary efficacy end point (absolute change from baseline) was analysed on the per protocol (PP) data. The mean of these scores is shown as a value that is a mean change (a decrease in pain score) from the baseline value.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

137 participants

Primary outcome timeframe

Mean of 24 hour pain intensity (absolute change from baseline)

Results posted on

2012-02-16

Participant Flow

First patient first visit 25 March 2010 and last patient last visit 17 Oct 2010. Five Hospital Investigator Centres

14 day screening period before planned surgery. Run-in period 48 hours, 2.5 day double-blind period after surgery

Participant milestones

Participant milestones
Measure	OXN Tablets Oxycodone/Naloxone prolonged release (PR) 20/10mg or 10/5mg tablets twice a day (BID) for 2.5 days (total = 5 doses)	OXY Tablets Oxycodone prolonged release (PR) 20mg or 10mg tablets twice a day (BID) for 2.5 days (total = 5 doses)
Overall Study STARTED	70	67
Overall Study COMPLETED	63	64
Overall Study NOT COMPLETED	7	3

Reasons for withdrawal

Reasons for withdrawal
Measure	OXN Tablets Oxycodone/Naloxone prolonged release (PR) 20/10mg or 10/5mg tablets twice a day (BID) for 2.5 days (total = 5 doses)	OXY Tablets Oxycodone prolonged release (PR) 20mg or 10mg tablets twice a day (BID) for 2.5 days (total = 5 doses)
Overall Study Adverse Event	0	1
Overall Study Protocol Violation	1	0
Overall Study Withdrawal by Subject	5	2
Overall Study Other	1	0

Baseline Characteristics

OXN PR Compared to OXY PR in Subjects With Postoperative Pain After Knee Arthroplasty

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OXN Tablets n=70 Participants Oxycodone/Naloxone prolonged release (PR) 20/10mg or 10/5mg tablets twice a day (BID) for 2.5 days (total = 5 doses)	OXY Tablets n=67 Participants Oxycodone prolonged release (PR) 20mg or 10mg tablets twice a day (BID) for 2.5 days (total = 5 doses)	Total n=137 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	36 Participants n=5 Participants	33 Participants n=7 Participants	69 Participants n=5 Participants
Age, Categorical >=65 years	34 Participants n=5 Participants	34 Participants n=7 Participants	68 Participants n=5 Participants
Age Continuous	64 years STANDARD_DEVIATION 6.7 • n=5 Participants	64 years STANDARD_DEVIATION 6.7 • n=7 Participants	64 years STANDARD_DEVIATION 6.7 • n=5 Participants
Sex: Female, Male Female	44 Participants n=5 Participants	39 Participants n=7 Participants	83 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	28 Participants n=7 Participants	54 Participants n=5 Participants
Region of Enrollment Finland	70 participants n=5 Participants	67 participants n=7 Participants	137 participants n=5 Participants

PRIMARY outcome

Timeframe: Mean of 24 hour pain intensity (absolute change from baseline)

Population: The primary efficacy end point (absolute change from baseline) was analysed on the PP data using a mixed model repeated measures of analysis of covariance (RMANCOVA).

Outcome measures

Outcome measures
Measure	OXN Tablets n=59 Participants Oxycodone/Naloxone prolonged release (PR) 20/10mg or 10/5mg tablets twice a day (BID) for 2.5 days (total = 5 doses). Mean baseline pain score = 3.4	OXY Tablets n=62 Participants Oxycodone prolonged release (PR) 20mg or 10mg tablets twice a day (BID) for 2.5 days (total = 5 doses). Mean baseline pain score = 3.1
Mean of 4 NRS Scores for 24 Hour Pain Intensity at Rest, Shown as Absolute Change From Baseline (i.e. a Decrease From the Baseline Value)	-1.2 Units on a scale Interval -1.5 to -0.9	-1.1 Units on a scale Interval -1.4 to -0.8

SECONDARY outcome

Timeframe: Mean dose during the whole double blind treatment phase (2.5 days)

Population: This is the per protocol population (PP), which is a subset of the full analysis population. The data presented is only for those subjects taking the higher dose (20/10 mg OXN or 20 mg OXY) in the study.

To compare the use of rescue analgesia for the 2 groups (OXN 20/10mg tablets and OXY 20mg tablets) during the double blind treatment phase. Rescue medication was given (OXY Immediate Release, 5mg capsules) if the subjects pain score on the (Numeric Rating Scale (NRS), 0 (no pain) to 10 (worst possible pain)), was greater than or equal to 4. The value presented is the mean dose over the double blind phase.

Outcome measures

Outcome measures
Measure	OXN Tablets n=36 Participants Oxycodone/Naloxone prolonged release (PR) 20/10mg or 10/5mg tablets twice a day (BID) for 2.5 days (total = 5 doses). Mean baseline pain score = 3.4	OXY Tablets n=33 Participants Oxycodone prolonged release (PR) 20mg or 10mg tablets twice a day (BID) for 2.5 days (total = 5 doses). Mean baseline pain score = 3.1
Mean Dose (mg) of Rescue Analgesia for the Treatment Phase for Subjects Taking 20/10mg OXN PR Tablets or 20mg OXY PR Tablets	24 mg of rescue analgesia Standard Deviation 28.7 • Interval 3.8 to 9.3	17 mg of rescue analgesia Standard Deviation 25.4 • Interval 5.9 to 18.5

Adverse Events

OXN Tablets

Serious events: 2 serious events

Other events: 43 other events

Deaths: 0 deaths

OXY Tablets

Serious events: 0 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	OXN Tablets n=70 participants at risk Oxycodone/Naloxone prolonged release (PR) 20/10mg or 10/5mg tablets twice a day (BID) for 2.5 days (total = 5 doses)	OXY Tablets n=67 participants at risk Oxycodone prolonged release (PR) 20mg or 10mg tablets twice a day (BID) for 2.5 days (total = 5 doses)
General disorders Mild pyrexia	1.4% 1/70 • Number of events 1 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	0.00% 0/67 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
General disorders severe neuropathic pain	1.4% 1/70 • Number of events 1 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	0.00% 0/67 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.

Other adverse events

Additional Information

Maggie Wilson

Mundipharma Research

Phone: + 4401223 424444

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	OXN Tablets n=70 participants at risk Oxycodone/Naloxone prolonged release (PR) 20/10mg or 10/5mg tablets twice a day (BID) for 2.5 days (total = 5 doses)	OXY Tablets n=67 participants at risk Oxycodone prolonged release (PR) 20mg or 10mg tablets twice a day (BID) for 2.5 days (total = 5 doses)
Gastrointestinal disorders abdominal discomfort	1.4% 1/70 • Number of events 1 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	0.00% 0/67 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
Gastrointestinal disorders constipation	37.1% 26/70 • Number of events 26 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	32.8% 22/67 • Number of events 22 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
Gastrointestinal disorders dyspepsia	1.4% 1/70 • Number of events 1 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	1.5% 1/67 • Number of events 1 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
Gastrointestinal disorders nausea	10.0% 7/70 • Number of events 7 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	11.9% 8/67 • Number of events 8 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
Gastrointestinal disorders vomiting	5.7% 4/70 • Number of events 4 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	4.5% 3/67 • Number of events 3 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
General disorders chest pain	0.00% 0/70 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	1.5% 1/67 • Number of events 1 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
General disorders fatigue	0.00% 0/70 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	1.5% 1/67 • Number of events 1 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
General disorders pain	0.00% 0/70 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	1.5% 1/67 • Number of events 1 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
General disorders pyrexia	0.00% 0/70 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	3.0% 2/67 • Number of events 2 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
Injury, poisoning and procedural complications excoriation	1.4% 1/70 • Number of events 1 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	0.00% 0/67 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
Injury, poisoning and procedural complications procedural headache	1.4% 1/70 • Number of events 1 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	0.00% 0/67 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
Musculoskeletal and connective tissue disorders arthralgia	0.00% 0/70 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	1.5% 1/67 • Number of events 1 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
Musculoskeletal and connective tissue disorders back pain	1.4% 1/70 • Number of events 1 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	0.00% 0/67 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
Musculoskeletal and connective tissue disorders muscle spasms	1.4% 1/70 • Number of events 1 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	0.00% 0/67 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
Nervous system disorders dizziness	4.3% 3/70 • Number of events 3 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	0.00% 0/67 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
Psychiatric disorders confusional state	0.00% 0/70 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	3.0% 2/67 • Number of events 2 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
Psychiatric disorders hallucination	1.4% 1/70 • Number of events 1 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	0.00% 0/67 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
Psychiatric disorders hallucination visual	0.00% 0/70 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	1.5% 1/67 • Number of events 1 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
Psychiatric disorders insomnia	2.9% 2/70 • Number of events 2 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	4.5% 3/67 • Number of events 3 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
Psychiatric disorders nightmare	1.4% 1/70 • Number of events 1 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	0.00% 0/67 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
Renal and urinary disorders oliguria	1.4% 1/70 • Number of events 1 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	0.00% 0/67 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
Skin and subcutaneous tissue disorders hyperhidrosis	1.4% 1/70 • Number of events 1 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	1.5% 1/67 • Number of events 1 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.
Skin and subcutaneous tissue disorders pruritus generalised	0.00% 0/70 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.	1.5% 1/67 • Number of events 1 • Adverse events were collected from informed consent until participation in trial was completed, this could be a minimum of 1 day to a maximum of 23 days. Adverse events were collected by spontaneous question and causality and severity were assigned by the investigator.