Trial Outcomes & Findings for Post-operative Dental Pain Study Comparing Two Different Dosage of Analgesic Efficacy (NCT NCT01075243)

NCT ID: NCT01075243

Last Updated: 2015-04-29

Results Overview

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 \[0-no relief, 1-little relief, 2-some relief, 3-a lot of relief, 4-complete relief\]

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 401 participants
• Primary outcome timeframe: Every two hours from Baseline to 6 hours post dose
• Results posted on: 2015-04-29

Participant Flow

Participants were recruited at the clinical site.

Of 722 screened participants, 321 were considered to be screen failures. Remaining 401 were randomized to study treatments.

Participant milestones

Measure	Paracetamol Caplet 1000 Milligrams (mg) Participants were administered with two paracetamol fast dissolving (FD) 500 mg caplets (Total dose= 1000 mg), and two placebo standard paracetamol caplets with 150 milliliter (mL) of water through oral route.	Paracetamol Caplet 650 mg Participants were administered with two standard paracetamol 325 mg caplets (Total dose = 650 mg) and two placebo FD caplets, with 150 mL of water through oral route.	Placebo Caplet Participants were administered with two standard and two FD placebo caplets, with 150 mL of water through oral route.
Overall Study STARTED	163	158	80
Overall Study COMPLETED	157	155	80
Overall Study NOT COMPLETED	6	3	0

Reasons for withdrawal

Measure	Paracetamol Caplet 1000 Milligrams (mg) Participants were administered with two paracetamol fast dissolving (FD) 500 mg caplets (Total dose= 1000 mg), and two placebo standard paracetamol caplets with 150 milliliter (mL) of water through oral route.	Paracetamol Caplet 650 mg Participants were administered with two standard paracetamol 325 mg caplets (Total dose = 650 mg) and two placebo FD caplets, with 150 mL of water through oral route.	Placebo Caplet Participants were administered with two standard and two FD placebo caplets, with 150 mL of water through oral route.
Overall Study Lost to Follow-up	5	2	0
Overall Study Withdrawal by Subject	1	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Paracetamol Caplet 1000mg n=163 Participants Participants were administered with two paracetamol FD 500 mg caplets (Total dose= 1000 mg), and two placebo standard paracetamol caplets with 150 mL of water through oral route.	Paracetamol Caplet 650 mg n=158 Participants Participants were administered with two standard paracetamol 325 mg caplets (Total dose = 650 mg) and two placebo FD caplets, with 150 mL of water through oral route.	Placebo Caplet n=80 Participants Participants were administered with two standard and two FD placebo caplets, with 150 mL of water through oral route.	Total n=401 Participants Total of all reporting groups
Age, Continuous	19.7 Years STANDARD_DEVIATION 2.26 • n=5 Participants	20.4 Years STANDARD_DEVIATION 2.81 • n=7 Participants	20.6 Years STANDARD_DEVIATION 2.76 • n=5 Participants	20.2 Years STANDARD_DEVIATION 2.61 • n=4 Participants
Sex: Female, Male Female	102 Participants n=5 Participants	104 Participants n=7 Participants	56 Participants n=5 Participants	262 Participants n=4 Participants
Sex: Female, Male Male	61 Participants n=5 Participants	54 Participants n=7 Participants	24 Participants n=5 Participants	139 Participants n=4 Participants
Number of participants with pain severity score measured on a rating scale Moderate	109 Participants n=5 Participants	106 Participants n=7 Participants	53 Participants n=5 Participants	268 Participants n=4 Participants
Number of participants with pain severity score measured on a rating scale Severe	54 Participants n=5 Participants	52 Participants n=7 Participants	27 Participants n=5 Participants	133 Participants n=4 Participants

PRIMARY outcome

Timeframe: Every two hours from Baseline to 6 hours post dose

Population: Intent to Treat (ITT) population: All participants who received one study treatment and have at least one post-baseline efficacy assessment.

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]

Outcome measures

Measure	Paracetamol Caplet 1000mg n=163 Participants Participants were administered with two paracetamol FD 500 mg caplets (Total dose= 1000 mg), and two placebo standard paracetamol caplets with 150 mL of water through oral route.	Paracetamol Caplet 650 mg n=158 Participants Participants were administered with two standard paracetamol 325 mg caplets (Total dose = 650 mg) and two placebo FD caplets, with 150 mL of water through oral route.	Placebo Caplet n=80 Participants Participants were administered with two standard and two FD placebo caplets, with 150 mL of water through oral route.
Sum of Pain Relief and Pain Intensity Differences From 0 to 6 Hours (SPRID 6 Hours)	16.08 Score on a scale Standard Deviation 10.68	12.42 Score on a scale Standard Deviation 9.89	4.63 Score on a scale Standard Deviation 8.82

SECONDARY outcome

Timeframe: Baseline to 6 hours post dose

Population: ITT population: All participants who received one study treatment and have at least one post-baseline efficacy assessment. Participants who did not achieve first perceptible pain relief during the 6 hours of the study period or took rescue medication were censored at the time 360 minutes.

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.

Outcome measures

Measure	Paracetamol Caplet 1000mg n=163 Participants Participants were administered with two paracetamol FD 500 mg caplets (Total dose= 1000 mg), and two placebo standard paracetamol caplets with 150 mL of water through oral route.	Paracetamol Caplet 650 mg n=158 Participants Participants were administered with two standard paracetamol 325 mg caplets (Total dose = 650 mg) and two placebo FD caplets, with 150 mL of water through oral route.	Placebo Caplet n=80 Participants Participants were administered with two standard and two FD placebo caplets, with 150 mL of water through oral route.
Time to Confirmed First Perceptible Relief	54.72 minutes Standard Deviation 104.911	69.67 minutes Standard Deviation 120.501	225.70 minutes Standard Deviation 162.884

SECONDARY outcome

Timeframe: Baseline to 6 hours post dose

Population: ITT population: All participants who received one study treatment and have at least one post-baseline efficacy assessment. Participants who did not achieve first perceptible pain relief during the 6 hours of the study period or took rescue medication were censored at the time 360 minutes.

Participants recorded the time to meaningful relief by stopping a second stopwatch when they first began to experience meaningful relief.

Outcome measures

Measure	Paracetamol Caplet 1000mg n=163 Participants Participants were administered with two paracetamol FD 500 mg caplets (Total dose= 1000 mg), and two placebo standard paracetamol caplets with 150 mL of water through oral route.	Paracetamol Caplet 650 mg n=158 Participants Participants were administered with two standard paracetamol 325 mg caplets (Total dose = 650 mg) and two placebo FD caplets, with 150 mL of water through oral route.	Placebo Caplet n=80 Participants Participants were administered with two standard and two FD placebo caplets, with 150 mL of water through oral route.
Time to Onset of Meaningful Pain Relief	70.53 minutes Standard Deviation 101.474	88.16 minutes Standard Deviation 115.955	247.14 minutes Standard Deviation 143.028

SECONDARY outcome

Timeframe: Baseline to 6 hours post dose

Population: ITT population: All participants who received one study treatment and had at least one post-baseline efficacy assessment. Participants who did not achieve first perceptible pain relief during the 6 hours of the study period or took rescue medication were censored.

Median time of use of rescue medication by participants.

Outcome measures

Measure	Paracetamol Caplet 1000mg n=163 Participants Participants were administered with two paracetamol FD 500 mg caplets (Total dose= 1000 mg), and two placebo standard paracetamol caplets with 150 mL of water through oral route.	Paracetamol Caplet 650 mg n=158 Participants Participants were administered with two standard paracetamol 325 mg caplets (Total dose = 650 mg) and two placebo FD caplets, with 150 mL of water through oral route.	Placebo Caplet n=80 Participants Participants were administered with two standard and two FD placebo caplets, with 150 mL of water through oral route.
Time to Start Using Rescue Medication	360.00 minutes Interval 124.0 to 360.0	314.00 minutes Interval 123.0 to 360.0	131.00 minutes Interval 115.0 to 360.0

SECONDARY outcome

Timeframe: Baseline to 2 hours post dose

Population: ITT population: All participants who received one study treatment and have at least one post-baseline efficacy assessment. Participants who did not achieve first perceptible pain relief during the 6 hours of the study period or took rescue medication were censored at the time 360 minutes.

Percentage of participants who received rescue medication at different time points post dose.

Outcome measures

Measure	Paracetamol Caplet 1000mg n=163 Participants Participants were administered with two paracetamol FD 500 mg caplets (Total dose= 1000 mg), and two placebo standard paracetamol caplets with 150 mL of water through oral route.	Paracetamol Caplet 650 mg n=158 Participants Participants were administered with two standard paracetamol 325 mg caplets (Total dose = 650 mg) and two placebo FD caplets, with 150 mL of water through oral route.	Placebo Caplet n=80 Participants Participants were administered with two standard and two FD placebo caplets, with 150 mL of water through oral route.
Percentage of Participants Who Took Rescue Medication at 2 Hours	0.00 Percentage of participants	0.00 Percentage of participants	1.30 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to 6 hours post dose

Population: ITT population: All participants who received one study treatment and have at least one post-baseline efficacy assessment. Participants who did not achieve first perceptible pain relief during the 6 hours of the study period or took rescue medication were censored at the time 360 minutes.

Percentage of participants who received rescue medication at different time points post dose.

Outcome measures

Measure	Paracetamol Caplet 1000mg n=163 Participants Participants were administered with two paracetamol FD 500 mg caplets (Total dose= 1000 mg), and two placebo standard paracetamol caplets with 150 mL of water through oral route.	Paracetamol Caplet 650 mg n=158 Participants Participants were administered with two standard paracetamol 325 mg caplets (Total dose = 650 mg) and two placebo FD caplets, with 150 mL of water through oral route.	Placebo Caplet n=80 Participants Participants were administered with two standard and two FD placebo caplets, with 150 mL of water through oral route.
Percentage of Participants Who Took Rescue Medication at 6 Hours	44.20 Percentage of participants	51.90 Percentage of participants	70.00 Percentage of participants

SECONDARY outcome

Timeframe: Every two hours from baseline to 2 hours post dose

Population: All participants who received one study treatment and have at least one post-baseline efficacy assessment. Participants who did not achieve first perceptible pain relief during the 6 hours of the study period or took rescue medication were censored at the time 360 minutes.

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

Outcome measures

Measure	Paracetamol Caplet 1000mg n=163 Participants Participants were administered with two paracetamol FD 500 mg caplets (Total dose= 1000 mg), and two placebo standard paracetamol caplets with 150 mL of water through oral route.	Paracetamol Caplet 650 mg n=158 Participants Participants were administered with two standard paracetamol 325 mg caplets (Total dose = 650 mg) and two placebo FD caplets, with 150 mL of water through oral route.	Placebo Caplet n=80 Participants Participants were administered with two standard and two FD placebo caplets, with 150 mL of water through oral route.
SPRID at 2 Hours	6.49 Score on a scale Standard Deviation 3.11	5.57 Score on a scale Standard Deviation 2.94	1.55 Score on a scale Standard Deviation 2.45

SECONDARY outcome

Timeframe: Every two hours from baseline to 4 hours post dose

Population: ITT population: All participants who received one study treatment and have at least one post-baseline efficacy assessment. Participants who did not achieve first perceptible pain relief during the 6 hours of the study period or took rescue medication were censored at the time 360 minutes.

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

Outcome measures

Measure	Paracetamol Caplet 1000mg n=163 Participants Participants were administered with two paracetamol FD 500 mg caplets (Total dose= 1000 mg), and two placebo standard paracetamol caplets with 150 mL of water through oral route.	Paracetamol Caplet 650 mg n=158 Participants Participants were administered with two standard paracetamol 325 mg caplets (Total dose = 650 mg) and two placebo FD caplets, with 150 mL of water through oral route.	Placebo Caplet n=80 Participants Participants were administered with two standard and two FD placebo caplets, with 150 mL of water through oral route.
SPRID at 4 Hours	12.09 Score on a scale Standard Deviation 6.93	9.45 Score on a scale Standard Deviation 6.19	3.00 Score on a scale Standard Deviation 5.27

SECONDARY outcome

Timeframe: Every two hours from baseline to 2 hours post dose

Population: ITT population: All participants who received one study treatment and have at least one post-baseline efficacy assessment. Participants who did not achieve first perceptible pain relief during the 6 hours of the study period or took rescue medication were censored at the time 360 minutes.

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].

Outcome measures

Measure	Paracetamol Caplet 1000mg n=163 Participants Participants were administered with two paracetamol FD 500 mg caplets (Total dose= 1000 mg), and two placebo standard paracetamol caplets with 150 mL of water through oral route.	Paracetamol Caplet 650 mg n=158 Participants Participants were administered with two standard paracetamol 325 mg caplets (Total dose = 650 mg) and two placebo FD caplets, with 150 mL of water through oral route.	Placebo Caplet n=80 Participants Participants were administered with two standard and two FD placebo caplets, with 150 mL of water through oral route.
Total Pain Relief Score (TOTPAR) at 2 Hours	4.31 Score on a scale Standard Deviation 1.88	3.80 Score on a scale Standard Deviation 1.89	1.36 Score on a scale Standard Deviation 1.59

SECONDARY outcome

Timeframe: Every two hours from baseline to 4 hours post dose

Population: ITT population: All participants who received one study treatment and have at least one post-baseline efficacy assessment. Participants who did not achieve first perceptible pain relief during the 6 hours of the study period or took rescue medication were censored at the time 360 minutes.

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].

Outcome measures

Measure	Paracetamol Caplet 1000mg n=163 Participants Participants were administered with two paracetamol FD 500 mg caplets (Total dose= 1000 mg), and two placebo standard paracetamol caplets with 150 mL of water through oral route.	Paracetamol Caplet 650 mg n=158 Participants Participants were administered with two standard paracetamol 325 mg caplets (Total dose = 650 mg) and two placebo FD caplets, with 150 mL of water through oral route.	Placebo Caplet n=80 Participants Participants were administered with two standard and two FD placebo caplets, with 150 mL of water through oral route.
TOTPAR at 4 Hours	8.21 Score on a scale Standard Deviation 4.10	6.64 Score on a scale Standard Deviation 3.97	2.79 Score on a scale Standard Deviation 3.46

SECONDARY outcome

Timeframe: Every two hours from baseline to 6 hours post dose

Population: ITT population: All participants who received one study treatment and have at least one post-baseline efficacy assessment. Participants who did not achieve first perceptible pain relief during the 6 hours of the study period or took rescue medication were censored at the time 360 minutes.

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].

Outcome measures

Measure	Paracetamol Caplet 1000mg n=163 Participants Participants were administered with two paracetamol FD 500 mg caplets (Total dose= 1000 mg), and two placebo standard paracetamol caplets with 150 mL of water through oral route.	Paracetamol Caplet 650 mg n=158 Participants Participants were administered with two standard paracetamol 325 mg caplets (Total dose = 650 mg) and two placebo FD caplets, with 150 mL of water through oral route.	Placebo Caplet n=80 Participants Participants were administered with two standard and two FD placebo caplets, with 150 mL of water through oral route.
TOTPAR at 6 Hours	11.06 Score on a scale Standard Deviation 6.41	8.83 Score on a scale Standard Deviation 6.30	4.29 Score on a scale Standard Deviation 5.80

SECONDARY outcome

Timeframe: Every two hours from baseline to 2 hours post dose

Population: ITT population: All participants who received one study treatment and have at least one post-baseline efficacy assessment. Participants who did not achieve first perceptible pain relief during the 6 hours of the study period or took rescue medication were censored at the time 360 minutes.

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.

Outcome measures

Measure	Paracetamol Caplet 1000mg n=163 Participants Participants were administered with two paracetamol FD 500 mg caplets (Total dose= 1000 mg), and two placebo standard paracetamol caplets with 150 mL of water through oral route.	Paracetamol Caplet 650 mg n=158 Participants Participants were administered with two standard paracetamol 325 mg caplets (Total dose = 650 mg) and two placebo FD caplets, with 150 mL of water through oral route.	Placebo Caplet n=80 Participants Participants were administered with two standard and two FD placebo caplets, with 150 mL of water through oral route.
Sum of Pain Intensity Difference (SPID) Scores at 2 Hours	2.17 Score on a scale Standard Deviation 1.37	1.77 Score on a scale Standard Deviation 1.20	0.19 Score on a scale Standard Deviation 1.03

SECONDARY outcome

Timeframe: Every two hours from baseline to 4 hours post dose

Population: ITT population: All participants who received one study treatment and have at least one post-baseline efficacy assessment. Participants who did not achieve first perceptible pain relief during the 6 hours of the study period or took rescue medication were censored at the time 360 minutes.

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.

Outcome measures

Measure	Paracetamol Caplet 1000mg n=163 Participants Participants were administered with two paracetamol FD 500 mg caplets (Total dose= 1000 mg), and two placebo standard paracetamol caplets with 150 mL of water through oral route.	Paracetamol Caplet 650 mg n=158 Participants Participants were administered with two standard paracetamol 325 mg caplets (Total dose = 650 mg) and two placebo FD caplets, with 150 mL of water through oral route.	Placebo Caplet n=80 Participants Participants were administered with two standard and two FD placebo caplets, with 150 mL of water through oral route.
SPID Scores at 4 Hours	3.88 Score on a scale Standard Deviation 3.06	2.81 Score on a scale Standard Deviation 2.52	0.20 Score on a scale Standard Deviation 2.13

SECONDARY outcome

Timeframe: Every two hours from baseline to 6 hours post dose

Population: ITT population: All participants who received one study treatment and have at least one post-baseline efficacy assessment. Participants who did not achieve first perceptible pain relief during the 6 hours of the study period or took rescue medication were censored at the time 360 minutes.

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.

Outcome measures

Measure	Paracetamol Caplet 1000mg n=163 Participants Participants were administered with two paracetamol FD 500 mg caplets (Total dose= 1000 mg), and two placebo standard paracetamol caplets with 150 mL of water through oral route.	Paracetamol Caplet 650 mg n=158 Participants Participants were administered with two standard paracetamol 325 mg caplets (Total dose = 650 mg) and two placebo FD caplets, with 150 mL of water through oral route.	Placebo Caplet n=80 Participants Participants were administered with two standard and two FD placebo caplets, with 150 mL of water through oral route.
SPID Scores at 6 Hours	5.02 Score on a scale Standard Deviation 4.63	3.59 Score on a scale Standard Deviation 4.01	0.34 Score on a scale Standard Deviation 3.51

SECONDARY outcome

Timeframe: Baseline to 6 hours post dose

Population: ITT population: All participants who received study treatment and had at least one post-baseline efficacy assessment.

PGART was measured by a score in a scale from 0-4: 0- Poor; 1- Fair 2- Good; 3- Very Good; 4- Excellent.

Outcome measures

Measure	Paracetamol Caplet 1000mg n=163 Participants Participants were administered with two paracetamol FD 500 mg caplets (Total dose= 1000 mg), and two placebo standard paracetamol caplets with 150 mL of water through oral route.	Paracetamol Caplet 650 mg n=158 Participants Participants were administered with two standard paracetamol 325 mg caplets (Total dose = 650 mg) and two placebo FD caplets, with 150 mL of water through oral route.	Placebo Caplet n=80 Participants Participants were administered with two standard and two FD placebo caplets, with 150 mL of water through oral route.
Participants Global Assessment to Response to Treatment (PGART)	2.20 Score on a scale Standard Deviation 1.13	1.80 Score on a scale Standard Deviation 1.18	0.80 Score on a scale Standard Deviation 1.05

Adverse Events

Paracetamol Caplet 1000mg

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

Paracetamol Caplet 650 mg

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

Placebo Caplet

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Paracetamol Caplet 1000mg n=163 participants at risk Participants were administered with two paracetamol FD 500 mg caplets (Total dose= 1000 mg), and two placebo standard paracetamol caplets with 150 mL of water through oral route.	Paracetamol Caplet 650 mg n=158 participants at risk Participants were administered with two standard paracetamol 325 mg caplets (Total dose = 650 mg) and two placebo FD caplets, with 150 mL of water through oral route.	Placebo Caplet n=80 participants at risk Participants were administered with two standard and two FD placebo caplets, with 150 mL of water through oral route.
Gastrointestinal disorders Nausea	10.4% 17/163 • Number of events 18 • All adverse events encountered or spontaneously reported following administration of any investigational product, or for up to 5 days after the last administration of investigational product were recorded.	10.8% 17/158 • Number of events 17 • All adverse events encountered or spontaneously reported following administration of any investigational product, or for up to 5 days after the last administration of investigational product were recorded.	8.8% 7/80 • Number of events 8 • All adverse events encountered or spontaneously reported following administration of any investigational product, or for up to 5 days after the last administration of investigational product were recorded.
Gastrointestinal disorders Vomiting	4.3% 7/163 • Number of events 7 • All adverse events encountered or spontaneously reported following administration of any investigational product, or for up to 5 days after the last administration of investigational product were recorded.	3.2% 5/158 • Number of events 5 • All adverse events encountered or spontaneously reported following administration of any investigational product, or for up to 5 days after the last administration of investigational product were recorded.	5.0% 4/80 • Number of events 4 • All adverse events encountered or spontaneously reported following administration of any investigational product, or for up to 5 days after the last administration of investigational product were recorded.
Nervous system disorders Headache	2.5% 4/163 • Number of events 4 • All adverse events encountered or spontaneously reported following administration of any investigational product, or for up to 5 days after the last administration of investigational product were recorded.	3.8% 6/158 • Number of events 6 • All adverse events encountered or spontaneously reported following administration of any investigational product, or for up to 5 days after the last administration of investigational product were recorded.	8.8% 7/80 • Number of events 7 • All adverse events encountered or spontaneously reported following administration of any investigational product, or for up to 5 days after the last administration of investigational product were recorded.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER