Ibuprofen/Acetaminophen Versus Nurofen Plus® and Panadeine® Extra Dental Pain Study

A Double-blind, 5 Parallel-group, Placebo-controlled, Randomised, Single Dose, 3-site Study to Compare the Analgesic Efficacy and Tolerability of a Combination of Ibuprofen 400 mg Plus Paracetamol 1000 mg; a Combination of Ibuprofen 200 mg Plus Paracetamol 500 mg; a Combination of Ibuprofen 400 mg Plus Codeine 25.6 mg (Nurofen Plus®); a Combination of Paracetamol 1000 mg Plus Codeine 30 mg (Panadeine® Extra) in Postoperative Adult Dental Pain Following Third Molar Extraction.

The objective is to assess the efficacy and tolerability of a combination of 400 mg ibuprofen plus 1000 mg acetaminophen, 200 mg ibuprofen plus 500 mg acetaminophen compared with Nurofen Plus® and Panadeine® Extra.

Study Overview

• Status: Completed
• Conditions: Post-operative Pain
• Intervention / Treatment: Drug: Ibuprofen/acetaminophen; Drug: Ibuprofen/acetaminophen (higher dose); Drug: Nurofen Plus®; Drug: Panadeine® Extra; Drug: Placebo

Detailed Description

RB has developed a fixed-dose combination of ibuprofen and acetaminophen (paracetamol). Since the pharmacological actions of ibuprofen and acetaminophen (paracetamol) differ in their site and mode of action, the combination would be expected to be more effective than either active alone, given that pain is multi-factorial with different mediators.

The purpose of this study was to compare the efficacy and tolerability of ibuprofen/acetaminophen (paracetamol) combination with leading market analgesics.

The efficacy and tolerability was assessed in terms of total analgesic effect, peak analgesic effect, onset and duration of action and the subject's overall assessment of the study medication.

• Study Type: Interventional
• Enrollment (Actual): 678
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78705
      • Premier Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

Experiencing moderate to severe pain after extraction of impacted third molars

Main Exclusion Criteria:

Any ongoing painful condition other than that associated with the current third molar surgery that could significantly interfere with the subject's suitability Any condition that would render the subject unsuitable to receive an NSAID, acetaminophen or codeine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ibuprofen/acetaminophen (lower dose); One tablet of ibuprofen 200 mg plus acetaminophen 500 mg and one placebo tablet	Drug: Ibuprofen/acetaminophen; One tablet of ibuprofen 200 mg plus acetaminophen 500 mg and one placebo tablet, single dose taken orally with 300 ml water; Other Names: Ibuprofen/paracetamol (lower dose)
Experimental: Ibuprofen/acetaminophen (higher dose); Two tablets of ibuprofen 200 mg plus acetaminophen 500 mg	Drug: Ibuprofen/acetaminophen (higher dose); Two tablets of ibuprofen 200 mg plus acetaminophen 500 mg, single dose taken orally with 300 ml water; Other Names: Ibuprofen/Paracetamol
Active Comparator: Nurofen Plus®; Two tablets ibuprofen 200mg plus codeine 12.8mg (Nurofen Plus®)	Drug: Nurofen Plus®; Two tablets ibuprofen 200mg plus codeine 12.8mg (Nurofen Plus®), single dose taken orally with 300 ml water; Other Names: Ibuprofen/Codeine
Active Comparator: Panadeine® Extra; Two tablets acetaminophen 500 mg plus codeine 15 mg (Panadeine® Extra)	Drug: Panadeine® Extra; Two tablets acetaminophen 500 mg plus codeine 15 mg (Panadeine® Extra), single dose taken orally with 300 ml water; Other Names: Acetaminophen/codeine; Paracetamol/codeine
Placebo Comparator: Placebo; Two placebo tablets	Drug: Placebo; Two placebo tablets, single dose taken orally with 300 ml water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Area Under the Curve (AUC) of Pain Intensity and Relief Scores (SPRID)	SPRID 0-12h: Sum of pain intensity difference (PID) and the pain relief (PR) score over the twelve-hour follow-up period. Score range: 0mm = No pain and 100mm = Worst pain. This was calculated as the area under the curve (AUC) using the method of linear trapezoids assuming that the baseline assessment took place at time zero. Pain intensity (PI) was measured by pain assessment questionnaire, where subject tick the appropriate box in a 4-point ordinal scale ranging from 0 = No pain, 1 = Mild pain, 2 = Moderate pain, and 3 = Severe pain, in response to the question 'What is your pain level at this time?' Total Pain Relief (TOTPAR) was measured using pain assessment diary, where subject tick the appropriate box on a 5-point Ordinal Rating Scale: 0 = None, 1 = A Little, 2 = Some, 3 = A Lot, and 4 = Complete, in response to the question 'How much relief have you had from your starting pain?'	0 (baseline), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in AUC (0-8h) of SPRID	SPRID 0-8h: Sum of pain intensity difference (PID) and the pain relief (PR) score over the twelve-hour follow-up period. Score range: 0 mm = No pain and 100 mm = Worst pain. This was calculated as the area under the curve (AUC) using the method of linear trapezoids assuming that the baseline assessment took place at time zero. Pain intensity (PI) was measured by pain assessment questionnaire, where subject tick the appropriate box in a 4-point ordinal scale ranging from 0 = No pain, 1 = Mild pain, 2 = Moderate pain, and 3 = Severe pain, in response to the question 'What is your pain level at this time?' Total Pain Relief (TOTPAR) was measured using pain assessment diary, where subject tick the appropriate box on a 5-point Ordinal Rating Scale: 0 = None, 1 = A Little, 2 = Some, 3 = A Lot, and 4 = Complete, in response to the question 'How much relief have you had from your starting pain?'	0 (baseline), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dose
Change From Baseline in AUC for Pain Intensity Difference Scores (SPID)	Sum of Pain Intensity Difference (SPID) was calculated as the area under the curve (AUC) using the method of linear trapezoids assuming that the baseline assessment took place at time zero. Score range: 0mm = No pain and 100mm = Worst pain. Pain intensity (PI) was measured by pain assessment questionnaire, where subject tick the appropriate box in a 4-point ordinal scale ranging from 0 = No pain, 1 = Mild pain, 2 = Moderate pain, and 3 = Severe pain, in response to the question 'What is your pain level at this time?'	0-4, 0-6, 0-8 and 0-12 hours
Change From Baseline in AUC of Pain Relief Scores (TOTPAR)	Total pain relief (TOTPAR) was measured using pain assessment diary where subject tick the appropriate box in response to the question 'How much relief have you had from your starting pain?' Pain Relief (PR) was rated on a 5-point Ordinal Rating Scale: 0 = None, 1 = A Little, 2 = Some, 3 = A Lot, and 4 = Complete.	0-4, 0-6, 0-8 and 0-12 hours
Change From Baseline in AUC of Individual Reading Pain Intensity and Relief Scores (SPRID)	SPRID 0-12h: Sum of pain intensity difference (PID) and the pain relief (PR) score over the twelve-hour follow-up period. Score range: 0mm = No pain and 100mm = Worst pain. This was calculated as the area under the curve (AUC) using the method of linear trapezoids assuming that the baseline assessment took place at time zero. Pain intensity (PI) was measured by pain assessment questionnaire, where subject tick the appropriate box in a 4-point ordinal scale ranging from 0 = No pain, 1 = Mild pain, 2 = Moderate pain, and 3 = Severe pain, in response to the question 'What is your pain level at this time?' Total Pain Relief (TOTPAR) was measured using pain assessment diary, where subject tick the appropriate box on a 5-point Ordinal Rating Scale: 0 = None, 1 = A Little, 2 = Some, 3 = A Lot, and 4 = Complete, in response to the question 'How much relief have you had from your starting pain?'	15, 30, 45, 60, 90 minutes and 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours
Individual Pain Intensity Differences (Ordinal)	Pain intensity (PI) was measured by pain assessment questionnaire where subject tick the appropriate box in response to the question 'What is your pain level at this time?' PI measured using a 4-point ordinal scale: 0 = No pain, 1 = Mild pain, 2 = Moderate pain, and 3 = Severe pain.	15, 30, 45, 60, 90 minutes and 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours
Individual Pain Intensity Differences Visual Analogue Scale (VAS)	Pain Intensity (PI) VAS was measured using a horizontal 100-mm VAS ranging 0 mm = 'No Pain' as the left anchor and 100 mm = 'Worst Pain' as the right anchor, labelled by the subject marking the VAS line in the pain assessment questionnaire in response to the instruction 'Please indicate with a line on the scale below your pain at this time.'	15, 30, 45, 60, 90 minutes and 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours
Change From Baseline in Peak Pain Intensity Difference (Peak PID - Ordinal)	Pain intensity (PI) was measured by pain assessment questionnaire where subject tick the appropriate box in response to the question 'What is your pain level at this time?' PI measured using a 4-point ordinal scale: 0 = No pain, 1 = Mild pain, 2 = Moderate pain, and 3 = Severe pain.	0 (baseline), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose
Change From Baseline in Peak Pain Relief (PR)	Total pain relief (TOTPAR) was measured using pain assessment diary where subject tick the appropriate box in response to the question 'How much relief have you had from your starting pain?' Pain Relief (PR) was rated on a 5-point Ordinal Rating Scale: 0 = None, 1 = A Little, 2 = Some, 3 = A Lot, and 4 = Complete.	0 (baseline), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose
Subjects' Overall Assessment of the Study Medication Assessed at 12 Hours or Just Before Administration of Rescue Medication	Subject's Overall Assessment measured by subject ticking the appropriate box in response to the question 'How effective do you think the study medication is as a treatment for pain?' Subject's Overall Assessment rated on a five-point ordinal scale: 1 = Poor, 2 = Fair, 3 = Good, 4 = Very good, and 5 = Excellent.	At 12 hours

Collaborators and Investigators

• Sponsor: Reckitt Benckiser LLC
• Collaborators: Premier Research Group plc; Aptuit Inc.
• Investigators: Principal Investigator: Stephen Daniels, Premier Research Group Inc

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: October 26, 2010
• First Submitted That Met QC Criteria: October 26, 2010
• First Posted (Estimate): October 27, 2010

Study Record Updates

• Last Update Posted (Actual): September 17, 2018
• Last Update Submitted That Met QC Criteria: August 14, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Dental pain; Ibuprofen; Acetaminophen; Paracetamol; Nurofen Plus®; Panadeine® Extra
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Stomatognathic Diseases; Tooth Diseases; Facial Pain; Pain, Postoperative; Toothache; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Acetaminophen; Ibuprofen; Codeine
• Other Study ID Numbers: NL0811