Trial Outcomes & Findings for A Study to Compare Oxycodone/Naloxone Prolonged Release Against Codeine/Paracetamol in the Treatment of Moderate to Severe Chronic Low Back Pain or Pain Due to Osteoarthritis (NCT NCT00784810)

NCT ID: NCT00784810

Last Updated: 2011-11-02

Results Overview

The primary objective was to demonstrate non inferiority of Oxycodone/Naloxone Prolonged Release (OXN PR) compared to codeine/paracetamol in moderate to severe pain as assessed by BS-11 average daily pain scores. The Box Scale-11 is a scale from 0 to 10 (i.e. 0, 1, 2...10), where the subject records their daily pain over the previous 24 hours, by circling the relevant box, where 0 = no pain and 10 = pain as bad as you can imagine. This value is the value recorded at week 12 (average pain over the last 24 hours)

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 247 participants
• Primary outcome timeframe: Average daily pain over last 24 hours (at Week 12)
• Results posted on: 2011-11-02

Participant Flow

Patients were recruited in primary and secondary care in the UK from 6 Feb 2009 to 24 Mar 2010

3-7 day screening, following 7-14 day run-in and a 12 week double-blind treatment period.

Participant milestones

Measure	Oxycodone/Naloxone Tablets (OXN) Oxycodone/Naloxone (OXN) tablets 5,10 and 20 mg	Codeine/Paracetamol Tablets Codeine/Paracetamol 15/500 and 30/500 mg
Overall Study STARTED	124	123
Overall Study COMPLETED	61	74
Overall Study NOT COMPLETED	63	49

Reasons for withdrawal

Measure	Oxycodone/Naloxone Tablets (OXN) Oxycodone/Naloxone (OXN) tablets 5,10 and 20 mg	Codeine/Paracetamol Tablets Codeine/Paracetamol 15/500 and 30/500 mg
Overall Study Adverse Event	32	20
Overall Study Lack of Efficacy	14	11
Overall Study Withdrawal by Subject	11	9
Overall Study Administrative	5	8
Overall Study Lost to Follow-up	1	1

Baseline Characteristics

A Study to Compare Oxycodone/Naloxone Prolonged Release Against Codeine/Paracetamol in the Treatment of Moderate to Severe Chronic Low Back Pain or Pain Due to Osteoarthritis

Baseline characteristics by cohort

Measure	Oxycodone/Naloxone Tablets (OXN) n=124 Participants Oxycodone/Naloxone (OXN) tablets 5,10 and 20 mg	Codeine/Paracetamol Tablets n=123 Participants Codeine/Paracetamol 15/500 and 30/500 mg	Total n=247 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	66 Participants n=5 Participants	70 Participants n=7 Participants	136 Participants n=5 Participants
Age, Categorical >=65 years	58 Participants n=5 Participants	53 Participants n=7 Participants	111 Participants n=5 Participants
Age Continuous	64.3 years STANDARD_DEVIATION 10.53 • n=5 Participants	63.9 years STANDARD_DEVIATION 10.97 • n=7 Participants	64.1 years STANDARD_DEVIATION 10.73 • n=5 Participants
Sex: Female, Male Female	77 Participants n=5 Participants	81 Participants n=7 Participants	158 Participants n=5 Participants
Sex: Female, Male Male	47 Participants n=5 Participants	42 Participants n=7 Participants	89 Participants n=5 Participants
Region of Enrollment United Kingdom	124 participants n=5 Participants	123 participants n=7 Participants	247 participants n=5 Participants

PRIMARY outcome

Timeframe: Average daily pain over last 24 hours (at Week 12)

Population: To achieve a study with 80% power at the 1-sided 5% sig level and define non-inferiority to be a relative different less than 1.2. A sample size of 98 subjects per treatment group was required, ie a total of 196 subjects completing the study. The lower number of participants is due to subject withdrawal or lack of data.

The primary objective was to demonstrate non inferiority of Oxycodone/Naloxone Prolonged Release (OXN PR) compared to codeine/paracetamol in moderate to severe pain as assessed by BS-11 average daily pain scores. The Box Scale-11 is a scale from 0 to 10 (i.e. 0, 1, 2...10), where the subject records their daily pain over the previous 24 hours, by circling the relevant box, where 0 = no pain and 10 = pain as bad as you can imagine. This value is the value recorded at week 12 (average pain over the last 24 hours)

Outcome measures

Measure	Oxycodone/Naloxone Tablets (OXN) n=60 Participants Oxycodone/Naloxone (OXN) tablets 5,10 and 20 mg	Codeine/Paracetamol Tablets n=80 Participants Codeine/Paracetamol 15/500 and 30/500 mg
Average Daily Pain Score Box Scale-11 (BS-11) Recorded at Week 12 (Average Pain Over Last 24 Hours)	4.2 Units on a BS-11 scale at Week 12 Standard Deviation 2.139	4.64 Units on a BS-11 scale at Week 12 Standard Deviation 2.046

SECONDARY outcome

Timeframe: Between visit 8 and 9

Population: The number of participants for analysis is less due to subject withdrawals or lack of data.

To compare the number of intakes of rescue medication use (ibuprofen) for breakthrough pain between OXN (Oxycodone/Naloxone) and codeine/paracetamol groups. Ibuprofen tablets (400mg up to 3 times per day) were available as rescue medication. This was recorded by the subject in their diary whenever it was taken. The discrepancy in numbers of patients at this stage (between Visit 8 and Visit 9) is due to subject withdrawal during the study. The mean values presented are the "number of intakes of rescue medication" for this period (ie between Visit 8 and Visit 9).

Outcome measures

Measure	Oxycodone/Naloxone Tablets (OXN) n=60 Participants Oxycodone/Naloxone (OXN) tablets 5,10 and 20 mg	Codeine/Paracetamol Tablets n=80 Participants Codeine/Paracetamol 15/500 and 30/500 mg
Number of Intakes of Rescue Medication (Ibuprofen) Between Visit 8 and Visit 9 for the 2 Groups.	13.2 Number of rescue medication intakes Standard Deviation 23.31	9.4 Number of rescue medication intakes Standard Deviation 19.94

Adverse Events

Oxycodone/Naloxone Tablets (OXN)

Serious events: 3 serious events

Other events: 27 other events

Deaths: 0 deaths

Codeine/Paracetamol Tablets

Serious events: 4 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Measure	Oxycodone/Naloxone Tablets (OXN) n=124 participants at risk Oxycodone/Naloxone (OXN) tablets 5,10 and 20 mg	Codeine/Paracetamol Tablets n=123 participants at risk Codeine/Paracetamol 15/500 and 30/500 mg
Musculoskeletal and connective tissue disorders joint effusion	0.81% 1/124 • Number of events 1 • approximately 3 - 4 months, treatment and outcome	0.00% 0/123 • approximately 3 - 4 months, treatment and outcome
Cardiac disorders carotid artery stenosis	0.81% 1/124 • Number of events 1 • approximately 3 - 4 months, treatment and outcome	0.00% 0/123 • approximately 3 - 4 months, treatment and outcome
Gastrointestinal disorders diarrhoea, rectal haemorrhage, abdominal pain	0.81% 1/124 • Number of events 1 • approximately 3 - 4 months, treatment and outcome	0.00% 0/123 • approximately 3 - 4 months, treatment and outcome
Blood and lymphatic system disorders Deep vein thrombosis	0.00% 0/124 • approximately 3 - 4 months, treatment and outcome	0.81% 1/123 • Number of events 1 • approximately 3 - 4 months, treatment and outcome
General disorders Head injfury	0.00% 0/124 • approximately 3 - 4 months, treatment and outcome	0.81% 1/123 • Number of events 1 • approximately 3 - 4 months, treatment and outcome
Cardiac disorders Atrial fibrillation	0.00% 0/124 • approximately 3 - 4 months, treatment and outcome	0.81% 1/123 • Number of events 1 • approximately 3 - 4 months, treatment and outcome
Cardiac disorders Angina Pectoris	0.00% 0/124 • approximately 3 - 4 months, treatment and outcome	0.81% 1/123 • Number of events 2 • approximately 3 - 4 months, treatment and outcome

Other adverse events

Measure	Oxycodone/Naloxone Tablets (OXN) n=124 participants at risk Oxycodone/Naloxone (OXN) tablets 5,10 and 20 mg	Codeine/Paracetamol Tablets n=123 participants at risk Codeine/Paracetamol 15/500 and 30/500 mg
Gastrointestinal disorders Constipation	6.5% 8/124 • approximately 3 - 4 months, treatment and outcome	5.7% 7/123 • approximately 3 - 4 months, treatment and outcome
Gastrointestinal disorders dyspepsia	3.2% 4/124 • approximately 3 - 4 months, treatment and outcome	4.9% 6/123 • approximately 3 - 4 months, treatment and outcome
Gastrointestinal disorders nausea	3.2% 4/124 • approximately 3 - 4 months, treatment and outcome	2.4% 3/123 • approximately 3 - 4 months, treatment and outcome
Gastrointestinal disorders haemorrhoids	0.00% 0/124 • approximately 3 - 4 months, treatment and outcome	3.3% 4/123 • approximately 3 - 4 months, treatment and outcome
Infections and infestations lower respiratory tract infection	5.6% 7/124 • approximately 3 - 4 months, treatment and outcome	3.3% 4/123 • approximately 3 - 4 months, treatment and outcome
Infections and infestations urinary tract infection	1.6% 2/124 • approximately 3 - 4 months, treatment and outcome	4.1% 5/123 • approximately 3 - 4 months, treatment and outcome
Infections and infestations bronchitis	1.6% 2/124 • approximately 3 - 4 months, treatment and outcome	2.4% 3/123 • approximately 3 - 4 months, treatment and outcome

Additional Information

Director of Medical Affairs

Napp Pharmaceuticals Ltd

Phone: 01223 424444

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place