Post-operative Dental Pain Study Comparing Two Different Dosage of Analgesic Efficacy

Phase 4

Completed

Conditions: Post-surgical Dental Pain

Interventions: Drug: Paracetamol 1000 mg
Drug: Paracetamol 650 mg
Drug: Placebo

Registration Number: NCT01075243

Lead Sponsor: GlaxoSmithKline

Brief Summary: GlaxoSmithKline will be conducting this trial to compare analgesic efficacy of paracetamol 1000 mg vs 650 mg. The post-surgical dental pain model will be used to evaluate the analgesic efficacy of paracetamol. Each subject will be enrolled in the study for up to six weeks. The duration of the entire study will be approximately 18 weeks. Each subject will have to come to the clinic for three visits (Screening, Treatment and Follow up visits).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 401

Inclusion Criteria

Subjects aged 18 to 45 years with moderate-to-severe dental pain as assessed by verbal rating scale (VRS) and confirmed by a score of at least 50 mm out of 100 mm using a visual analogue (VAS) following the surgical removal of up to two mandibular third molars. If only one mandibular third molar is removed, it must be a full bony impaction. If two mandibular third molars are removed, both may be partial bony impactions OR there may be a combination of one full bony impaction with the second tooth being erupted, soft tissue impaction, or partial bony impaction. Ipsilateral maxillary third molars may be removed at the surgeon's discretion, regardless of impaction level.

Exclusion Criteria

Pregnant and lactating females
Allergy/intolerance to study materials or nitrous oxide or local anaesthetic used during surgery
Current or recurrent liver, kidney or cardiac disease, stomach ulcers, gastrointestinal bleeding, gastroesophageal reflux disease, bronchospasm, rhinitis, urticaria or asthma

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Paracetamol 1000mg	Paracetamol 1000 mg	Paracetamol 1000mg
Paracetamol 650 mg	Paracetamol 650 mg	Paracetamol 650 mg
Placebo	Placebo	Placebo

Primary Outcome Measures

Name	Time	Method
Sum of Pain Relief and Pain Intensity Differences From 0 to 6 Hours (SPRID 6 Hours)	Every two hours from Baseline to 6 hours post dose	SPRID:Sum of Pain Intensity Difference (SPID) and Total Pain Relief (TOTPAR) at each post-dosing time-point. SPRID score ranged from -5.8 (least pain relief) to 40.3 (highest pain relief). SPID and TOTPAR were calculated as weighted sums of Pain Intensity Differences (PID) and Pain Relief Scores (PRS) at each measurement time, respectively. PID was derived by subtracting the pain severity score at a given post-dosing time-point from the baseline \[pain severity score range:0-no pain, 1-mild pain, 2-moderate pain, 3-severe pain using a 4-point categorical Verbal Rating Scale (VRS)\]. If the subject rated pain intensity as 2 or 3, pain was assessed using a 100 mm Visual Analog Scale (VAS) \[0 (no pain), 100 (worst pain)\]. VAS scores were converted into PID scores by subtracting them from baseline pain scores. PRS was assessed on 5-point categorical pain relief rating scale \[0-no relief, 1-little relief, 2-some relief, 3-a lot of relief, 4-complete relief\]

Secondary Outcome Measures

Name	Time	Method
Time to Start Using Rescue Medication	Baseline to 6 hours post dose	Median time of use of rescue medication by participants.
Percentage of Participants Who Took Rescue Medication at 6 Hours	Baseline to 6 hours post dose	Percentage of participants who received rescue medication at different time points post dose.
Percentage of Participants Who Took Rescue Medication at 2 Hours	Baseline to 2 hours post dose	Percentage of participants who received rescue medication at different time points post dose.
SPRID at 2 Hours	Every two hours from baseline to 2 hours post dose	SPRID:Sum of Pain Intensity Difference (SPID) and Total Pain Relief (TOTPAR) at each post-dosing time-point. SPRID score ranged from -1.8 (least pain relief) to 12.3 (highest pain relief). SPID and TOTPAR were calculated as weighted sums of Pain Intensity Differences (PID) and Pain Relief Scores (PRS) at each measurement time, respectively. PID was derived by subtracting the pain severity score at a given post-dosing time-point from the baseline \[pain severity score range:0-no pain, 1-mild pain, 2-moderate pain, 3-severe pain using a 4-point categorical Verbal Rating Scale (VRS)\]. If the subject rated pain intensity as 2 or 3, pain was assessed using a 100 mm Visual Analog Scale (VAS) \[0 (no pain), 100 (worst pain)\]. VAS scores were converted into PID scores by subtracting them from baseline pain scores. PRS was assessed on 5-point categorical pain relief rating scale \[0-no relief, 1-little relief, 2-some relief, 3-a lot of relief, 4-complete relief
SPID Scores at 4 Hours	Every two hours from baseline to 4 hours post dose	SPID was calculated as sum of products of Pain Intensity Differences (PID) at a given time-point (t) with the time-interval from that time-point to the previous time-point (t-1). The time-intervals used were 0-15, 15-30, 30-45, 45-60, 60-90, 90-120, 120-240. Positive and higher scores indicate greater reduction in pain. SPIDt = ∑PID x (timet - timet-1) Pain Intensity was assessed at baseline and at each time-point based on a 4-point categorical Verbal Rating Scale (VRS) scale: 0-no pain, 1-mild pain, 2-moderate pain, 3-severe pain. If the subject rated pain intensity as "2" or "3", pain was assessed using a 100 mm Visual Analog Scale (VAS) \[0 (no pain), 100 (worst pain)\]. VAS scores were converted into PID scores by subtracting them from pain scores taken at baseline.
Time to Confirmed First Perceptible Relief	Baseline to 6 hours post dose	Participants recorded the time to first perceptible relief by starting the first stopwatch at the time of dosing and stopping it when he/she experienced the first perceptible pain relief. The first perceptible pain relief was confirmed if the participant also stopped the second stopwatch indicating meaningful relief.
Time to Onset of Meaningful Pain Relief	Baseline to 6 hours post dose	Participants recorded the time to meaningful relief by stopping a second stopwatch when they first began to experience meaningful relief.
Sum of Pain Intensity Difference (SPID) Scores at 2 Hours	Every two hours from baseline to 2 hours post dose	SPID was calculated as sum of products of Pain Intensity Differences (PID) at a given time-point (t) with the time-interval from that time-point to the previous time-point (t-1). The time-intervals used were 0-15, 15-30, 30-45, 45-60, 60-90, 90-120. Positive and higher scores indicate greater reduction in pain. SPIDt = ∑PID x (timet - timet-1) Pain Intensity was assessed at baseline and at each time-point based on a 4-point categorical Verbal Rating Scale (VRS) scale: 0-no pain, 1-mild pain, 2-moderate pain, 3-severe pain. If the subject rated pain intensity as "2" or "3", pain was assessed using a 100 mm Visual Analog Scale (VAS) \[0 (no pain), 100 (worst pain)\]. VAS scores were converted into PID scores by subtracting them from pain scores taken at baseline.
SPRID at 4 Hours	Every two hours from baseline to 4 hours post dose	SPRID:Sum of Pain Intensity Difference (SPID) and Total Pain Relief (TOTPAR) at each post-dosing time-point. SPRID score ranged from -3.8 (least pain relief) to 26.3 (highest pain relief). SPID and TOTPAR were calculated as weighted sums of Pain Intensity Differences (PID) and Pain Relief Scores (PRS) at each measurement time, respectively. PID was derived by subtracting the pain severity score at a given post-dosing time-point from the baseline \[pain severity score range:0-no pain, 1-mild pain, 2-moderate pain, 3-severe pain using a 4-point categorical Verbal Rating Scale (VRS)\]. If the subject rated pain intensity as 2 or 3, pain was assessed using a 100 mm Visual Analog Scale (VAS) \[0 (no pain), 100 (worst pain)\]. VAS scores were converted into PID scores by subtracting them from baseline pain scores. PRS was assessed on 5-point categorical pain relief rating scale \[0-no relief, 1-little relief, 2-some relief, 3-a lot of relief, 4-complete relief
Total Pain Relief Score (TOTPAR) at 2 Hours	Every two hours from baseline to 2 hours post dose	TOTPAR was calculated as sum of products of pain relief (PR) at a given time-point (t) with the time-interval from that time-point to the previous time-point (t-1). The time-intervals used were 0-15, 15-30, 30-45, 45-60, 60-90, 90-120. Higher score indicated greater pain relief. TOTPARt = ∑PR x (timet - timet-1). PR score was assessed at each of the above time-points based on a 5-point categorical scale \[0-no relief, 1-little relief, 2-meaningful relief, 3-a lot of relief, 4-complete relief\].
TOTPAR at 4 Hours	Every two hours from baseline to 4 hours post dose	TOTPAR was calculated as sum of products of pain relief (PR) at a given time-point (t) with the time-interval from that time-point to the previous time-point (t-1). The time-intervals used were 0-15, 15-30, 30-45, 45-60, 60-90, 90-120, 120-240. Higher score indicated greater pain relief. TOTPARt = ∑PR x (timet - timet-1). PR score was assessed at each of the above time-points based on a 5-point categorical scale \[0-no relief, 1-little relief, 2-meaningful relief, 3-a lot of relief, 4-complete relief\].
SPID Scores at 6 Hours	Every two hours from baseline to 6 hours post dose	SPID was calculated as sum of products of Pain Intensity Differences (PID) at a given time-point (t) with the time-interval from that time-point to the previous time-point (t-1). The time-intervals used were 0-15, 15-30, 30-45, 45-60, 60-90, 90-120, 120-240, 240-300 and 300-360. Positive and higher scores indicate greater reduction in pain. SPIDt = ∑PID x (timet - timet-1) Pain Intensity was assessed at baseline and at each time-point based on a 4-point categorical Verbal Rating Scale (VRS) scale: 0-no pain, 1-mild pain, 2-moderate pain, 3-severe pain. If the subject rated pain intensity as "2" or "3", pain was assessed using a 100 mm Visual Analog Scale (VAS) \[0 (no pain), 100 (worst pain)\]. VAS scores were converted into PID scores by subtracting them from pain scores taken at baseline.
Participants Global Assessment to Response to Treatment (PGART)	Baseline to 6 hours post dose	PGART was measured by a score in a scale from 0-4: 0- Poor; 1- Fair 2- Good; 3- Very Good; 4- Excellent.
TOTPAR at 6 Hours	Every two hours from baseline to 6 hours post dose	TOTPAR was calculated as sum of products of pain relief (PR) at a given time-point (t) with the time-interval from that time-point to the previous time-point (t-1). The time-intervals used were 0-15, 15-30, 30-45, 45-60, 60-90, 90-120, 120-240, 240-300 and 300-360. Higher score indicated greater pain relief. TOTPARt = ∑PR x (timet - timet-1). PR score was assessed at each of the above time-points based on a 5-point categorical scale \[0-no relief, 1-little relief, 2-meaningful relief, 3-a lot of relief, 4-complete relief\].