Trial Outcomes & Findings for Clinical Study to Evaluate Efficacy of New Paracetamol Formulation Compared to Ibuprofen in Headache (NCT NCT01842633)

NCT ID: NCT01842633

Last Updated: 2017-09-01

Results Overview

SPID was calculated as the weighted sum of Pain (Headache) intensity differences at 4 hours post dose. The time-intervals used were 0-10, 10-15, 15-20, 20-25, 25-30, 30-40, 40-50, 50-60, 60-90, 90-120, 120-180, 180-240 minutes. The range of SPID at 4 hours post dose was from -12 to 4". PID was calculated as difference of pain intensity (PI) at baseline (prior to the first dose) with PI at a given time point. PI was assessed on a 4-point scale (0-no headache, 1-mild headache, 2-moderate headache, 3-severe headache).

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 365 participants
• Primary outcome timeframe: Up to 4 hours post dose
• Results posted on: 2017-09-01

Participant Flow

Participants were recruited at clinical sites in the United States.

365 participants were enrolled in the study out of which 165 participants were randomized in the study. 200 participants were not randomized for the following reasons: 165 were screening failure, 3 due to Adverse Events (AEs), 7 were lost to follow-up, 19 withdrawals by participant, and 6 due to other reasons.

Participant milestones

Measure	Paracetamol/ Caffeine Caplets Participants were administered with two caplets of paracetamol/caffeine combination 500/65milligram (mg) plus 2 placebo caplets orally with 8 ounces of water	Ibuprofen Caplets Participants were administered with two caplets of ibuprofen 200mg plus 2 placebo caplets orally with 8 ounces of water	Placebo Caplets Participants were administered with four placebo caplets with 8 ounces of water
Overall Study STARTED	65	66	34
Overall Study COMPLETED	62	64	34
Overall Study NOT COMPLETED	3	2	0

Reasons for withdrawal

Measure	Paracetamol/ Caffeine Caplets Participants were administered with two caplets of paracetamol/caffeine combination 500/65milligram (mg) plus 2 placebo caplets orally with 8 ounces of water	Ibuprofen Caplets Participants were administered with two caplets of ibuprofen 200mg plus 2 placebo caplets orally with 8 ounces of water	Placebo Caplets Participants were administered with four placebo caplets with 8 ounces of water
Overall Study Screen Failure	1	0	0
Overall Study Adverse Event	1	1	0
Overall Study Withdrawal by Subject	0	1	0
Overall Study Technical issues	1	0	0

Baseline Characteristics

Clinical Study to Evaluate Efficacy of New Paracetamol Formulation Compared to Ibuprofen in Headache

Baseline characteristics by cohort

Measure	Paracetamol/ Caffeine Caplets n=62 Participants Participants were administered with two caplets of paracetamol/caffeine combination 500/65mg plus 2 placebo caplets orally with 8 ounces of water	Ibuprofen Caplets n=62 Participants Participants were administered with two caplets of ibuprofen 200mg plus 2 placebo caplets orally with 8 ounces of water	Placebo Caplets n=33 Participants Participants were administered with four placebo caplets orally with 8 ounces of water	Total n=157 Participants Total of all reporting groups
Age, Continuous	39.9 Years STANDARD_DEVIATION 11.39 • n=5 Participants	38.1 Years STANDARD_DEVIATION 13.13 • n=7 Participants	38.5 Years STANDARD_DEVIATION 12.65 • n=5 Participants	38.9 Years STANDARD_DEVIATION 12.32 • n=4 Participants
Sex: Female, Male Female	46 Participants n=5 Participants	44 Participants n=7 Participants	23 Participants n=5 Participants	113 Participants n=4 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	18 Participants n=7 Participants	10 Participants n=5 Participants	44 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	14 Participants n=4 Participants
Race (NIH/OMB) White	56 Participants n=5 Participants	55 Participants n=7 Participants	28 Participants n=5 Participants	139 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 4 hours post dose

Population: Intention-to-treat (ITT) population defined as all participants who received treatment and who had at least one post-baseline efficacy assessment.

SPID was calculated as the weighted sum of Pain (Headache) intensity differences at 4 hours post dose. The time-intervals used were 0-10, 10-15, 15-20, 20-25, 25-30, 30-40, 40-50, 50-60, 60-90, 90-120, 120-180, 180-240 minutes. The range of SPID at 4 hours post dose was from -12 to 4". PID was calculated as difference of pain intensity (PI) at baseline (prior to the first dose) with PI at a given time point. PI was assessed on a 4-point scale (0-no headache, 1-mild headache, 2-moderate headache, 3-severe headache).

Outcome measures

Measure	Paracetamol/ Caffeine Caplets n=62 Participants Participants were administered with two caplets of paracetamol/caffeine combination 500/65mg plus two placebo caplets orally with eight ounce of water	Ibuprofen Caplets n=62 Participants Participants were administered with two caplets of ibuprofen 200mg plus two placebo caplets orally with eight ounce of water	Placebo Caplets n=33 Participants Participants were administered with four placebo caplets orally with eight ounce of water
Sum of Pain Intensity Difference (SPID) of Treatment and Placebo at 4 Hours	-6.13 score on a scale Standard Deviation 2.164	-5.78 score on a scale Standard Deviation 2.098	-5.86 score on a scale Standard Deviation 2.339

SECONDARY outcome

Timeframe: From (Baseline) 0 to 1 hour, 0 to 2 hours, and 0 to 3 hours post dose

Population: ITT population defined as all participants who received treatment and who had at least one post-baseline efficacy assessment.

SPID was calculated as the weighted sum of Pain (Headache) intensity differences at 1, 2 and 3 hours post dose.

The time-intervals used were 0-10, 10-15, 15-20, 20-25, 25-30, 30-40, 40-50, 50-60 minutes for SPID at 1 hour post dose. The range of SPID at 1 hour post dose was from -3 to 1. The time-intervals used were 0-10, 10-15, 15-20, 20-25, 25-30, 30-40, 40-50, 50-60, 60-90, 90-120 minutes for SPID at 2 hours post dose . The range of SPID at 2 hours post dose was from -6 to 2. The time-intervals used were 0-10, 10-15, 15-20, 20-25, 25-30, 30-40, 40-50, 50-60, 60-90, 90-120, 120-180 minutes for SPID at 3 hours post dose. The range of SPID at 3 hours post dose was from -9 to 3. PID was calculated as difference of pain intensity (PI) at baseline (prior to the first dose) with PI at a given time point. PI was assessed on a 4-point scale (0-no headache, 1-mild headache, 2-moderate headache, 3-severe headache).

Outcome measures

Measure	Paracetamol/ Caffeine Caplets n=62 Participants Participants were administered with two caplets of paracetamol/caffeine combination 500/65mg plus two placebo caplets orally with eight ounce of water	Ibuprofen Caplets n=62 Participants Participants were administered with two caplets of ibuprofen 200mg plus two placebo caplets orally with eight ounce of water	Placebo Caplets n=33 Participants Participants were administered with four placebo caplets orally with eight ounce of water
Sum of Pain Intensity Difference (SPID) at 1, 2 and 3 Hours At 1 hour (n=62, 61, 33)	-0.64 score on a scale Standard Deviation 0.488	-0.56 score on a scale Standard Deviation 0.418	-0.57 score on a scale Standard Deviation 0.505
Sum of Pain Intensity Difference (SPID) at 1, 2 and 3 Hours At 2 hour (n=62, 61, 33)	-2.21 score on a scale Standard Deviation 1.106	-2.02 score on a scale Standard Deviation 1.002	-2.04 score on a scale Standard Deviation 1.088
Sum of Pain Intensity Difference (SPID) at 1, 2 and 3 Hours At 3 hour (n=61, 62, 32)	-4.09 score on a scale Standard Deviation 1.524	-3.86 score on a scale Standard Deviation 1.342	-3.97 score on a scale Standard Deviation 1.528

SECONDARY outcome

Timeframe: Baseline up to 4 hours

Population: ITT population defined as all participants who received treatment and who had at least one post-baseline efficacy assessment.

Outcome measures

Measure	Paracetamol/ Caffeine Caplets n=62 Participants Participants were administered with two caplets of paracetamol/caffeine combination 500/65mg plus two placebo caplets orally with eight ounce of water	Ibuprofen Caplets n=62 Participants Participants were administered with two caplets of ibuprofen 200mg plus two placebo caplets orally with eight ounce of water	Placebo Caplets n=33 Participants Participants were administered with four placebo caplets orally with eight ounce of water
Number of Participants With Perceptible Pain Relief number of participants	62 number of participants	61 number of participants	33 number of participants
Number of Participants With Perceptible Pain Relief number of censored participants	0 number of participants	1 number of participants	0 number of participants

SECONDARY outcome

Timeframe: Baseline up to 4 hours

Population: ITT population defined as all participants who received treatment and who had at least one post-baseline efficacy assessment.

Time to perceptible headache relief was assessed as the time when participants achieve pain relief scores (PRS) more than or equal to 1.

Outcome measures

Measure	Paracetamol/ Caffeine Caplets n=62 Participants Participants were administered with two caplets of paracetamol/caffeine combination 500/65mg plus two placebo caplets orally with eight ounce of water	Ibuprofen Caplets n=62 Participants Participants were administered with two caplets of ibuprofen 200mg plus two placebo caplets orally with eight ounce of water	Placebo Caplets n=33 Participants Participants were administered with four placebo caplets orally with eight ounce of water
Time to Perceptible Headache Relief	27.00 minutes (min.) Full Range 31.274 • Interval 6.0 to 140.3	29.67 minutes (min.) Full Range 41.173 • Interval 8.7 to 240.0	27.00 minutes (min.) Full Range 38.042 • Interval 4.0 to 156.7

SECONDARY outcome

Timeframe: Baseline up to 4 hours

Population: ITT population defined as all participants who received treatment and who had at least one post-baseline efficacy assessment.

Outcome measures

Measure	Paracetamol/ Caffeine Caplets n=62 Participants Participants were administered with two caplets of paracetamol/caffeine combination 500/65mg plus two placebo caplets orally with eight ounce of water	Ibuprofen Caplets n=62 Participants Participants were administered with two caplets of ibuprofen 200mg plus two placebo caplets orally with eight ounce of water	Placebo Caplets n=33 Participants Participants were administered with four placebo caplets orally with eight ounce of water
Number of Participants With Meaningful Pain Relief number of participants	61 number of participants	60 number of participants	32 number of participants
Number of Participants With Meaningful Pain Relief number of censored participants	1 number of participants	2 number of participants	1 number of participants

SECONDARY outcome

Timeframe: Baseline up to 4 hours

Population: ITT population defined as all participants who received treatment and who had at least one post-baseline efficacy assessment.

Time to meaningful headache relief was assessed as time when participants reported a PRS ≥ 2.

Outcome measures

Measure	Paracetamol/ Caffeine Caplets n=62 Participants Participants were administered with two caplets of paracetamol/caffeine combination 500/65mg plus two placebo caplets orally with eight ounce of water	Ibuprofen Caplets n=62 Participants Participants were administered with two caplets of ibuprofen 200mg plus two placebo caplets orally with eight ounce of water	Placebo Caplets n=33 Participants Participants were administered with four placebo caplets orally with eight ounce of water
Time to Meaningful Headache Relief	43.33 min. Full Range 49.342 • Interval 11.7 to 240.0	54.17 min. Full Range 49.095 • Interval 16.7 to 240.0	46.67 min. Full Range 61.477 • Interval 12.5 to 240.0

SECONDARY outcome

Timeframe: From (Baseline) 0 to 1, from 0 to 2, from 0 to 3 and from 0 to 4 hour post dose

Population: ITT population defined as all participants who received treatment and who had at least one post-baseline efficacy assessment.

TOTPAR was calculated as the weighted sum of pain relief scores (PRS) at each time point. PRS was assessed on a 5-point scale (0-no relief, 1-a little relief, 2-some relief, 3-a lot of relief, and 4-complete relief). The range for TOTPAR for different time points were as follows: from 0 to 4 for TOTPAR at 1 hour post dose, from 0 to 8 for TOTPAR at 2 hours post dose, from 0 to 12 for TOTPAR at 3 hours post dose, and from 0 to 16 for TOTPAR at 4 hours post dose.

Outcome measures

Measure	Paracetamol/ Caffeine Caplets n=62 Participants Participants were administered with two caplets of paracetamol/caffeine combination 500/65mg plus two placebo caplets orally with eight ounce of water	Ibuprofen Caplets n=62 Participants Participants were administered with two caplets of ibuprofen 200mg plus two placebo caplets orally with eight ounce of water	Placebo Caplets n=33 Participants Participants were administered with four placebo caplets orally with eight ounce of water
Total Pain Relief (TOTPAR) Baseline-4 hour (59, 59, 33)	11.57 score on a scale Standard Deviation 3.373	11.05 score on a scale Standard Deviation 3.774	10.47 score on a scale Standard Deviation 4.053
Total Pain Relief (TOTPAR) Baseline-1 hour (62, 61, 33)	1.31 score on a scale Standard Deviation 0.922	1.17 score on a scale Standard Deviation 0.801	1.14 score on a scale Standard Deviation 0.864
Total Pain Relief (TOTPAR) Baseline-2 hour (62, 61, 33)	4.28 score on a scale Standard Deviation 1.818	4.05 score on a scale Standard Deviation 1.740	3.82 score on a scale Standard Deviation 1.886
Total Pain Relief (TOTPAR) Baseline-3 hour (61, 62, 33)	7.84 score on a scale Standard Deviation 2.337	7.51 score on a scale Standard Deviation 2.250	7.35 score on a scale Standard Deviation 2.463

SECONDARY outcome

Timeframe: From (Baseline) 0 to 1 hour, 0 to 2 hours, 0 to 3 hours and 0 to 4 hours post dose

Population: ITT population defined as all participants who received treatment and who had at least one post-baseline efficacy assessment.

SPRID was measured as sum of TOTPAR and SPID. SPID and TOTPAR were calculated as weighted sums of PID and PRS at each measurement time point, respectively. PID at each time point was calculated as difference of PI at baseline (prior to the first dose) with PI at a given time point. PI was assessed on a 4-point scale (0-no headache, 1-mild headache, 2-moderate headache, 3-severe headache). PRS was assessed on a 5-point scale (0-no relief, 1-a little relief, 2-some relief, 3-a lot of relief, and 4-complete relief). The range of SPRID for different time points were as follow: from-3 to 5 for SPRID at 1 hour post dose, from -6 to 10 for SPRID at 2 hours post dose, from -9 to 15 for SPRID at 3 hours post dose, and from -12 to 20 for SPRID at 4 hours post dose.

Outcome measures

Measure	Paracetamol/ Caffeine Caplets n=62 Participants Participants were administered with two caplets of paracetamol/caffeine combination 500/65mg plus two placebo caplets orally with eight ounce of water	Ibuprofen Caplets n=62 Participants Participants were administered with two caplets of ibuprofen 200mg plus two placebo caplets orally with eight ounce of water	Placebo Caplets n=33 Participants Participants were administered with four placebo caplets orally with eight ounce of water
Area Under the Time-Response Curve for Change in Headache Intensity and Headache Relief (SPRID) At 1 hour (n=62, 61, 33)	0.67 score on a scale Standard Deviation 0.505	0.61 score on a scale Standard Deviation 0.424	0.57 score on a scale Standard Deviation 0.473
Area Under the Time-Response Curve for Change in Headache Intensity and Headache Relief (SPRID) At 2 hour (n=62, 61, 33)	2.07 score on a scale Standard Deviation 0.957	2.03 score on a scale Standard Deviation 0.933	1.78 score on a scale Standard Deviation 1.116
Area Under the Time-Response Curve for Change in Headache Intensity and Headache Relief (SPRID) At 3 hour (n=61, 62, 32)	3.75 score on a scale Standard Deviation 1.250	3.64 score on a scale Standard Deviation 1.285	3.38 score on a scale Standard Deviation 1.581
Area Under the Time-Response Curve for Change in Headache Intensity and Headache Relief (SPRID) At 4 hour (n=59, 59, 33)	5.44 score on a scale Standard Deviation 1.890	5.28 score on a scale Standard Deviation 2.126	4.61 score on a scale Standard Deviation 2.613

SECONDARY outcome

Timeframe: 4 hours

Population: ITT population defined as all participants who received treatment and who had at least one post-baseline efficacy assessment.

Global evaluation of treatment response was measured by a score in a scale from: 0-very poor, 1-poor, 2-neutral [neither poor nor good], 3-good, or 4-very good).

Outcome measures

Measure	Paracetamol/ Caffeine Caplets n=62 Participants Participants were administered with two caplets of paracetamol/caffeine combination 500/65mg plus two placebo caplets orally with eight ounce of water	Ibuprofen Caplets n=62 Participants Participants were administered with two caplets of ibuprofen 200mg plus two placebo caplets orally with eight ounce of water	Placebo Caplets n=33 Participants Participants were administered with four placebo caplets orally with eight ounce of water
Global Evaluation of Response to Treatment	2.88 score on a scale Standard Deviation 0.740	2.81 score on a scale Standard Deviation 0.834	2.66 score on a scale Standard Deviation 0.946

SECONDARY outcome

Timeframe: 4 hours

Population: ITT population defined as all participants who received treatment, who took rescue medication and who had at least one post-baseline efficacy assessment.

Number of participants that took rescue medication over the total number of participants for a given treatment group

Outcome measures

Measure	Paracetamol/ Caffeine Caplets n=62 Participants Participants were administered with two caplets of paracetamol/caffeine combination 500/65mg plus two placebo caplets orally with eight ounce of water	Ibuprofen Caplets n=62 Participants Participants were administered with two caplets of ibuprofen 200mg plus two placebo caplets orally with eight ounce of water	Placebo Caplets n=33 Participants Participants were administered with four placebo caplets orally with eight ounce of water
Rate of Rescue Medication	2 number of participants	4 number of participants	4 number of participants

SECONDARY outcome

Timeframe: At 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 180, and 240 min.

Population: ITT population defined as all participants who received treatment and who had at least one post-baseline efficacy assessment.

Change from baseline in headache pain intensity was calculated as the change (difference) from baseline PI with PI at each time-point. PI was assessed on a 4-point scale (0-no headache, 1-mild headache, 2-moderate headache, 3-severe headache).

Outcome measures

Measure	Paracetamol/ Caffeine Caplets n=62 Participants Participants were administered with two caplets of paracetamol/caffeine combination 500/65mg plus two placebo caplets orally with eight ounce of water	Ibuprofen Caplets n=62 Participants Participants were administered with two caplets of ibuprofen 200mg plus two placebo caplets orally with eight ounce of water	Placebo Caplets n=33 Participants Participants were administered with four placebo caplets orally with eight ounce of water
Change From Baseline in Headache Pain Intensity At 40 min.	-0.92 score on a scale Standard Deviation 0.727	-0.75 score on a scale Standard Deviation 0.618	-0.75 score on a scale Standard Deviation 0.729
Change From Baseline in Headache Pain Intensity At 50 min.	-1.07 score on a scale Standard Deviation 0.769	-0.93 score on a scale Standard Deviation 0.736	-0.96 score on a scale Standard Deviation 0.725
Change From Baseline in Headache Pain Intensity At 60 min.	-1.26 score on a scale Standard Deviation 0.831	-1.17 score on a scale Standard Deviation 0.751	-1.14 score on a scale Standard Deviation 0.706
Change From Baseline in Headache Pain Intensity At 90 min.	-1.51 score on a scale Standard Deviation 0.748	-1.48 score on a scale Standard Deviation 0.708	-1.39 score on a scale Standard Deviation 0.733
Change From Baseline in Headache Pain Intensity At 120 min.	-1.76 score on a scale Standard Deviation 0.704	-1.73 score on a scale Standard Deviation 0.727	-1.69 score on a scale Standard Deviation 0.725
Change From Baseline in Headache Pain Intensity At 180 min.	-1.95 score on a scale Standard Deviation 0.529	-1.90 score on a scale Standard Deviation 0.530	-1.93 score on a scale Standard Deviation 0.561
Change From Baseline in Headache Pain Intensity At 240 min.	-2.01 score on a scale Standard Deviation 0.575	-1.91 score on a scale Standard Deviation 0.609	-1.95 score on a scale Standard Deviation 0.591
Change From Baseline in Headache Pain Intensity At 10 min.	-0.03 score on a scale Standard Deviation 0.166	-0.01 score on a scale Standard Deviation 0.064	-0.04 score on a scale Standard Deviation 0.211
Change From Baseline in Headache Pain Intensity At 15 min.	-0.10 score on a scale Standard Deviation 0.322	-0.06 score on a scale Standard Deviation 0.208	-0.10 score on a scale Standard Deviation 0.366
Change From Baseline in Headache Pain Intensity At 20 min.	-0.27 score on a scale Standard Deviation 0.439	-0.21 score on a scale Standard Deviation 0.359	-0.21 score on a scale Standard Deviation 0.464
Change From Baseline in Headache Pain Intensity At 25 min.	-0.45 score on a scale Standard Deviation 0.501	-0.34 score on a scale Standard Deviation 0.438	-0.36 score on a scale Standard Deviation 0.582
Change From Baseline in Headache Pain Intensity At 30 min.	-0.66 score on a scale Standard Deviation 0.625	-0.51 score on a scale Standard Deviation 0.531	-0.55 score on a scale Standard Deviation 0.697

SECONDARY outcome

Timeframe: At 10 min. 15 min., 20 min., 25 min., 30 min., 40 min., 50 min., 60 min., 90 min., 120 min., 180 min., 240 min.,

Population: ITT population defined as all participants who received treatment and who had at least one post-baseline efficacy assessment.

The participant assessed headache relief of each treated qualifying headache at 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 180, and 240 minutes post treatment on a 5-point scale (0-no relief, 1-a little relief, 2-some relief, 3-a lot of relief, and 4-complete relief). higher headache relief score indicates better outcome.

Outcome measures

Measure	Paracetamol/ Caffeine Caplets n=62 Participants Participants were administered with two caplets of paracetamol/caffeine combination 500/65mg plus two placebo caplets orally with eight ounce of water	Ibuprofen Caplets n=62 Participants Participants were administered with two caplets of ibuprofen 200mg plus two placebo caplets orally with eight ounce of water	Placebo Caplets n=33 Participants Participants were administered with four placebo caplets orally with eight ounce of water
Headache Relief 10 min.	0.07 score on a scale Standard Deviation 0.301	0.03 score on a scale Standard Deviation 0.140	0.11 score on a scale Standard Deviation 0.379
Headache Relief 15 min.	0.33 score on a scale Standard Deviation 0.660	0.16 score on a scale Standard Deviation 0.374	0.27 score on a scale Standard Deviation 0.635
Headache Relief 20 min.	0.68 score on a scale Standard Deviation 0.870	0.49 score on a scale Standard Deviation 0.670	0.60 score on a scale Standard Deviation 0.876
Headache Relief 25 min.	1.06 score on a scale Standard Deviation 1.059	0.77 score on a scale Standard Deviation 0.870	0.88 score on a scale Standard Deviation 0.986
Headache Relief 30 min.	1.37 score on a scale Standard Deviation 1.158	1.17 score on a scale Standard Deviation 1.072	1.22 score on a scale Standard Deviation 1.107
Headache Relief 40 min.	1.86 score on a scale Standard Deviation 1.341	1.62 score on a scale Standard Deviation 1.195	1.49 score on a scale Standard Deviation 1.182
Headache Relief 50 min.	2.15 score on a scale Standard Deviation 1.404	1.91 score on a scale Standard Deviation 1.356	1.82 score on a scale Standard Deviation 1.218
Headache Relief 60 min.	2.42 score on a scale Standard Deviation 1.380	2.34 score on a scale Standard Deviation 1.255	2.14 score on a scale Standard Deviation 1.213
Headache Relief 90 min.	2.85 score on a scale Standard Deviation 1.249	2.91 score on a scale Standard Deviation 1.162	2.68 score on a scale Standard Deviation 1.196
Headache Relief 120 min.	3.35 score on a scale Standard Deviation 0.962	3.37 score on a scale Standard Deviation 1.113	3.03 score on a scale Standard Deviation 1.206
Headache Relief 180 min.	3.69 score on a scale Standard Deviation 0.749	3.59 score on a scale Standard Deviation 0.907	3.44 score on a scale Standard Deviation 0.978
Headache Relief 240 min.	3.72 score on a scale Standard Deviation 0.795	3.55 score on a scale Standard Deviation 1.138	3.32 score on a scale Standard Deviation 1.155

SECONDARY outcome

Timeframe: 1 hour and 2 hour post dose

Population: ITT population defined as all participants who received treatment and who had at least one post-baseline efficacy assessment.

Number of participants with complete relief was calculated as the number of participants who reported PRS = 4-complete relief at 1 hour and 2 hours post dose.

Outcome measures

Measure	Paracetamol/ Caffeine Caplets n=62 Participants Participants were administered with two caplets of paracetamol/caffeine combination 500/65mg plus two placebo caplets orally with eight ounce of water	Ibuprofen Caplets n=62 Participants Participants were administered with two caplets of ibuprofen 200mg plus two placebo caplets orally with eight ounce of water	Placebo Caplets n=33 Participants Participants were administered with four placebo caplets orally with eight ounce of water
Number of Pain Free Participants At 1 hour	18 number of participants	17 number of participants	6 number of participants
Number of Pain Free Participants At 2 hour	38 number of participants	41 number of participants	20 number of participants

SECONDARY outcome

Timeframe: Up to 4 hours

Population: ITT population defined as all participants who received treatment and who had at least one post-baseline efficacy assessment

Time taken by the participants to use the rescue medication

Outcome measures

Measure	Paracetamol/ Caffeine Caplets n=62 Participants Participants were administered with two caplets of paracetamol/caffeine combination 500/65mg plus two placebo caplets orally with eight ounce of water	Ibuprofen Caplets n=62 Participants Participants were administered with two caplets of ibuprofen 200mg plus two placebo caplets orally with eight ounce of water	Placebo Caplets n=33 Participants Participants were administered with four placebo caplets orally with eight ounce of water
Time to the Use of Rescue Medication.	239.00 Minutes Standard Deviation 6.86	235.14 Minutes Standard Deviation 24.06	235.55 Minutes Standard Deviation 12.8

Adverse Events

Paracetamol/ Caffeine Caplets

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Ibuprofen Caplets

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo Caplets

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Paracetamol/ Caffeine Caplets n=62 participants at risk Participants were administered with two caplets of paracetamol/caffeine combination 500/65mg plus 2 placebo caplets orally with 8 ounce of water	Ibuprofen Caplets n=62 participants at risk Participants were administered with two caplets of ibuprofen 200mg plus 2 placebo caplets orally with 8 ounce of water	Placebo Caplets n=33 participants at risk Participants were administered with four placebo caplets orally with 8 ounce of water
Gastrointestinal disorders Dyspepsia	1.6% 1/62	0.00% 0/62	0.00% 0/33
Infections and infestations Nasopharyngitis	1.6% 1/62	0.00% 0/62	0.00% 0/33
Infections and infestations VIRAL UPPER RESPIRATORY TRACT INFECTION	1.6% 1/62	0.00% 0/62	0.00% 0/33
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	0.00% 0/62	0.00% 0/62	3.0% 1/33
Endocrine disorders HYPOTHYROIDISM	1.6% 1/62	0.00% 0/62	0.00% 0/33
General disorders FEELING JITTERY	1.6% 1/62	0.00% 0/62	0.00% 0/33
Psychiatric disorders DEPRESSION	0.00% 0/62	1.6% 1/62	0.00% 0/33
Psychiatric disorders INSOMNIA	0.00% 0/62	1.6% 1/62	0.00% 0/33
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	0.00% 0/62	1.6% 1/62	0.00% 0/33
Respiratory, thoracic and mediastinal disorders PARANASAL SINUS DISCOMFORT	0.00% 0/62	1.6% 1/62	0.00% 0/33
Respiratory, thoracic and mediastinal disorders SINUS CONGESTION	0.00% 0/62	1.6% 1/62	0.00% 0/33

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