Pain
Conditions
Brief summary
The purpose of this multi-center study is to assess the efficacy of headache relief of new paracetamol/caffeine formulation compared to placebo and ibuprofen in episodic tension-type headache (ETTH).
Interventions
Caplets containing 500 milligrams (mg) of paracetamol and 65 mg of caffeine
DRUGIbuprofen
Caplets containing 200 mg of ibuprofen
OTHERPlacebo
Matching placebo caplets
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants in good general health, and with diagnosis of ETTH with following conditions: 1. number of days with the condition is historically greater than or equal to two per month; 2. severity of headaches is historically at least moderate; 3. duration of headaches is historically more than or equal to 4 hours, if untreated.
Exclusion criteria
* Participant with known or suspected hypersensitivity, allergy, intolerance or contraindication to the use of any of the study medications * Participant has chronic tension type headache, psychiatric disease or a significant cognitive disorder, or any chronic pain disorder. * Participant currently taking or has taken medications or herbal supplements within the three months that are likely to interfere with the validity of subject-rated assessments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sum of Pain Intensity Difference (SPID) of Treatment and Placebo at 4 Hours | Up to 4 hours post dose | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Perceptible Pain Relief | Baseline up to 4 hours | — |
| Time to Perceptible Headache Relief | Baseline up to 4 hours | Time to perceptible headache relief was assessed as the time when participants achieve pain relief scores (PRS) more than or equal to 1. |
| Number of Participants With Meaningful Pain Relief | Baseline up to 4 hours | — |
| Time to Meaningful Headache Relief | Baseline up to 4 hours | Time to meaningful headache relief was assessed as time when participants reported a PRS ≥ 2. |
| Total Pain Relief (TOTPAR) | From (Baseline) 0 to 1, from 0 to 2, from 0 to 3 and from 0 to 4 hour post dose | 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. |
| Area Under the Time-Response Curve for Change in Headache Intensity and Headache Relief (SPRID) | From (Baseline) 0 to 1 hour, 0 to 2 hours, 0 to 3 hours and 0 to 4 hours post dose | 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. |
| Sum of Pain Intensity Difference (SPID) at 1, 2 and 3 Hours | From (Baseline) 0 to 1 hour, 0 to 2 hours, and 0 to 3 hours post dose | 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). |
| Rate of Rescue Medication | 4 hours | Number of participants that took rescue medication over the total number of participants for a given treatment group |
| Change From Baseline in Headache Pain Intensity | At 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 180, and 240 min. | 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). |
| Headache Relief | 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., | 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. |
| Number of Pain Free Participants | 1 hour and 2 hour post dose | 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. |
| Time to the Use of Rescue Medication. | Up to 4 hours | Time taken by the participants to use the rescue medication |
| Global Evaluation of Response to Treatment | 4 hours | 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). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at clinical sites in the United States.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Paracetamol/ Caffeine Caplets Participants were administered with two caplets of paracetamol/caffeine combination 500/65mg plus 2 placebo caplets orally with 8 ounces of water | 62 |
| Ibuprofen Caplets Participants were administered with two caplets of ibuprofen 200mg plus 2 placebo caplets orally with 8 ounces of water | 62 |
| Placebo Caplets Participants were administered with four placebo caplets orally with 8 ounces of water | 33 |
| Total | 157 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 |
| Overall Study | Screen Failure | 1 | 0 | 0 |
| Overall Study | Technical issues | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Paracetamol/ Caffeine Caplets | Ibuprofen Caplets | Placebo Caplets | Total |
|---|---|---|---|---|
| Age, Continuous | 39.9 Years STANDARD_DEVIATION 11.39 | 38.1 Years STANDARD_DEVIATION 13.13 | 38.5 Years STANDARD_DEVIATION 12.65 | 38.9 Years STANDARD_DEVIATION 12.32 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 6 Participants | 4 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 56 Participants | 55 Participants | 28 Participants | 139 Participants |
| Sex: Female, Male Female | 46 Participants | 44 Participants | 23 Participants | 113 Participants |
| Sex: Female, Male Male | 16 Participants | 18 Participants | 10 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 62 | 3 / 62 | 1 / 33 |
| serious Total, serious adverse events | 0 / 62 | 0 / 62 | 0 / 33 |
Outcome results
Primary
Sum of Pain Intensity Difference (SPID) of Treatment and Placebo at 4 Hours
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).
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paracetamol/ Caffeine Caplets | Sum of Pain Intensity Difference (SPID) of Treatment and Placebo at 4 Hours | -6.13 score on a scale | Standard Deviation 2.164 |
| Ibuprofen Caplets | Sum of Pain Intensity Difference (SPID) of Treatment and Placebo at 4 Hours | -5.78 score on a scale | Standard Deviation 2.098 |
| Placebo Caplets | Sum of Pain Intensity Difference (SPID) of Treatment and Placebo at 4 Hours | -5.86 score on a scale | Standard Deviation 2.339 |
95% CI: [-1.36, 0.42]
Secondary
Area Under the Time-Response Curve for Change in Headache Intensity and Headache Relief (SPRID)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paracetamol/ Caffeine Caplets | 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 |
| Paracetamol/ Caffeine Caplets | 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 1.89 |
| Paracetamol/ Caffeine Caplets | 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 1.25 |
| Paracetamol/ Caffeine Caplets | 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 |
| Ibuprofen Caplets | Area Under the Time-Response Curve for Change in Headache Intensity and Headache Relief (SPRID) | At 3 hour (n=61, 62, 32) | 3.64 score on a scale | Standard Deviation 1.285 |
| Ibuprofen Caplets | Area Under the Time-Response Curve for Change in Headache Intensity and Headache Relief (SPRID) | At 1 hour (n=62, 61, 33) | 0.61 score on a scale | Standard Deviation 0.424 |
| Ibuprofen Caplets | Area Under the Time-Response Curve for Change in Headache Intensity and Headache Relief (SPRID) | At 2 hour (n=62, 61, 33) | 2.03 score on a scale | Standard Deviation 0.933 |
| Ibuprofen Caplets | Area Under the Time-Response Curve for Change in Headache Intensity and Headache Relief (SPRID) | At 4 hour (n=59, 59, 33) | 5.28 score on a scale | Standard Deviation 2.126 |
| Placebo Caplets | Area Under the Time-Response Curve for Change in Headache Intensity and Headache Relief (SPRID) | At 2 hour (n=62, 61, 33) | 1.78 score on a scale | Standard Deviation 1.116 |
| Placebo Caplets | Area Under the Time-Response Curve for Change in Headache Intensity and Headache Relief (SPRID) | At 1 hour (n=62, 61, 33) | 0.57 score on a scale | Standard Deviation 0.473 |
| Placebo Caplets | Area Under the Time-Response Curve for Change in Headache Intensity and Headache Relief (SPRID) | At 4 hour (n=59, 59, 33) | 4.61 score on a scale | Standard Deviation 2.613 |
| Placebo Caplets | Area Under the Time-Response Curve for Change in Headache Intensity and Headache Relief (SPRID) | At 3 hour (n=61, 62, 32) | 3.38 score on a scale | Standard Deviation 1.581 |
Secondary
Change From Baseline in Headache Pain Intensity
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paracetamol/ Caffeine Caplets | Change From Baseline in Headache Pain Intensity | At 10 min. | -0.03 score on a scale | Standard Deviation 0.166 |
| Paracetamol/ Caffeine Caplets | Change From Baseline in Headache Pain Intensity | At 15 min. | -0.10 score on a scale | Standard Deviation 0.322 |
| Paracetamol/ Caffeine Caplets | Change From Baseline in Headache Pain Intensity | At 20 min. | -0.27 score on a scale | Standard Deviation 0.439 |
| Paracetamol/ Caffeine Caplets | Change From Baseline in Headache Pain Intensity | At 25 min. | -0.45 score on a scale | Standard Deviation 0.501 |
| Paracetamol/ Caffeine Caplets | Change From Baseline in Headache Pain Intensity | At 30 min. | -0.66 score on a scale | Standard Deviation 0.625 |
| Paracetamol/ Caffeine Caplets | Change From Baseline in Headache Pain Intensity | At 40 min. | -0.92 score on a scale | Standard Deviation 0.727 |
| Paracetamol/ Caffeine Caplets | Change From Baseline in Headache Pain Intensity | At 50 min. | -1.07 score on a scale | Standard Deviation 0.769 |
| Paracetamol/ Caffeine Caplets | Change From Baseline in Headache Pain Intensity | At 60 min. | -1.26 score on a scale | Standard Deviation 0.831 |
| Paracetamol/ Caffeine Caplets | Change From Baseline in Headache Pain Intensity | At 90 min. | -1.51 score on a scale | Standard Deviation 0.748 |
| Paracetamol/ Caffeine Caplets | Change From Baseline in Headache Pain Intensity | At 120 min. | -1.76 score on a scale | Standard Deviation 0.704 |
| Paracetamol/ Caffeine Caplets | Change From Baseline in Headache Pain Intensity | At 180 min. | -1.95 score on a scale | Standard Deviation 0.529 |
| Paracetamol/ Caffeine Caplets | Change From Baseline in Headache Pain Intensity | At 240 min. | -2.01 score on a scale | Standard Deviation 0.575 |
| Ibuprofen Caplets | Change From Baseline in Headache Pain Intensity | At 240 min. | -1.91 score on a scale | Standard Deviation 0.609 |
| Ibuprofen Caplets | Change From Baseline in Headache Pain Intensity | At 10 min. | -0.01 score on a scale | Standard Deviation 0.064 |
| Ibuprofen Caplets | Change From Baseline in Headache Pain Intensity | At 50 min. | -0.93 score on a scale | Standard Deviation 0.736 |
| Ibuprofen Caplets | Change From Baseline in Headache Pain Intensity | At 90 min. | -1.48 score on a scale | Standard Deviation 0.708 |
| Ibuprofen Caplets | Change From Baseline in Headache Pain Intensity | At 15 min. | -0.06 score on a scale | Standard Deviation 0.208 |
| Ibuprofen Caplets | Change From Baseline in Headache Pain Intensity | At 40 min. | -0.75 score on a scale | Standard Deviation 0.618 |
| Ibuprofen Caplets | Change From Baseline in Headache Pain Intensity | At 180 min. | -1.90 score on a scale | Standard Deviation 0.53 |
| Ibuprofen Caplets | Change From Baseline in Headache Pain Intensity | At 20 min. | -0.21 score on a scale | Standard Deviation 0.359 |
| Ibuprofen Caplets | Change From Baseline in Headache Pain Intensity | At 60 min. | -1.17 score on a scale | Standard Deviation 0.751 |
| Ibuprofen Caplets | Change From Baseline in Headache Pain Intensity | At 30 min. | -0.51 score on a scale | Standard Deviation 0.531 |
| Ibuprofen Caplets | Change From Baseline in Headache Pain Intensity | At 25 min. | -0.34 score on a scale | Standard Deviation 0.438 |
| Ibuprofen Caplets | Change From Baseline in Headache Pain Intensity | At 120 min. | -1.73 score on a scale | Standard Deviation 0.727 |
| Placebo Caplets | Change From Baseline in Headache Pain Intensity | At 25 min. | -0.36 score on a scale | Standard Deviation 0.582 |
| Placebo Caplets | Change From Baseline in Headache Pain Intensity | At 30 min. | -0.55 score on a scale | Standard Deviation 0.697 |
| Placebo Caplets | Change From Baseline in Headache Pain Intensity | At 120 min. | -1.69 score on a scale | Standard Deviation 0.725 |
| Placebo Caplets | Change From Baseline in Headache Pain Intensity | At 40 min. | -0.75 score on a scale | Standard Deviation 0.729 |
| Placebo Caplets | Change From Baseline in Headache Pain Intensity | At 50 min. | -0.96 score on a scale | Standard Deviation 0.725 |
| Placebo Caplets | Change From Baseline in Headache Pain Intensity | At 60 min. | -1.14 score on a scale | Standard Deviation 0.706 |
| Placebo Caplets | Change From Baseline in Headache Pain Intensity | At 180 min. | -1.93 score on a scale | Standard Deviation 0.561 |
| Placebo Caplets | Change From Baseline in Headache Pain Intensity | At 10 min. | -0.04 score on a scale | Standard Deviation 0.211 |
| Placebo Caplets | Change From Baseline in Headache Pain Intensity | At 15 min. | -0.10 score on a scale | Standard Deviation 0.366 |
| Placebo Caplets | Change From Baseline in Headache Pain Intensity | At 90 min. | -1.39 score on a scale | Standard Deviation 0.733 |
| Placebo Caplets | Change From Baseline in Headache Pain Intensity | At 20 min. | -0.21 score on a scale | Standard Deviation 0.464 |
| Placebo Caplets | Change From Baseline in Headache Pain Intensity | At 240 min. | -1.95 score on a scale | Standard Deviation 0.591 |
Secondary
Global Evaluation of Response to Treatment
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).
Time frame: 4 hours
Population: ITT population defined as all participants who received treatment and who had at least one post-baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paracetamol/ Caffeine Caplets | Global Evaluation of Response to Treatment | 2.88 score on a scale | Standard Deviation 0.74 |
| Ibuprofen Caplets | Global Evaluation of Response to Treatment | 2.81 score on a scale | Standard Deviation 0.834 |
| Placebo Caplets | Global Evaluation of Response to Treatment | 2.66 score on a scale | Standard Deviation 0.946 |
Secondary
Headache Relief
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paracetamol/ Caffeine Caplets | Headache Relief | 90 min. | 2.85 score on a scale | Standard Deviation 1.249 |
| Paracetamol/ Caffeine Caplets | Headache Relief | 120 min. | 3.35 score on a scale | Standard Deviation 0.962 |
| Paracetamol/ Caffeine Caplets | Headache Relief | 25 min. | 1.06 score on a scale | Standard Deviation 1.059 |
| Paracetamol/ Caffeine Caplets | Headache Relief | 180 min. | 3.69 score on a scale | Standard Deviation 0.749 |
| Paracetamol/ Caffeine Caplets | Headache Relief | 240 min. | 3.72 score on a scale | Standard Deviation 0.795 |
| Paracetamol/ Caffeine Caplets | Headache Relief | 10 min. | 0.07 score on a scale | Standard Deviation 0.301 |
| Paracetamol/ Caffeine Caplets | Headache Relief | 30 min. | 1.37 score on a scale | Standard Deviation 1.158 |
| Paracetamol/ Caffeine Caplets | Headache Relief | 40 min. | 1.86 score on a scale | Standard Deviation 1.341 |
| Paracetamol/ Caffeine Caplets | Headache Relief | 20 min. | 0.68 score on a scale | Standard Deviation 0.87 |
| Paracetamol/ Caffeine Caplets | Headache Relief | 50 min. | 2.15 score on a scale | Standard Deviation 1.404 |
| Paracetamol/ Caffeine Caplets | Headache Relief | 15 min. | 0.33 score on a scale | Standard Deviation 0.66 |
| Paracetamol/ Caffeine Caplets | Headache Relief | 60 min. | 2.42 score on a scale | Standard Deviation 1.38 |
| Ibuprofen Caplets | Headache Relief | 15 min. | 0.16 score on a scale | Standard Deviation 0.374 |
| Ibuprofen Caplets | Headache Relief | 90 min. | 2.91 score on a scale | Standard Deviation 1.162 |
| Ibuprofen Caplets | Headache Relief | 20 min. | 0.49 score on a scale | Standard Deviation 0.67 |
| Ibuprofen Caplets | Headache Relief | 30 min. | 1.17 score on a scale | Standard Deviation 1.072 |
| Ibuprofen Caplets | Headache Relief | 120 min. | 3.37 score on a scale | Standard Deviation 1.113 |
| Ibuprofen Caplets | Headache Relief | 10 min. | 0.03 score on a scale | Standard Deviation 0.14 |
| Ibuprofen Caplets | Headache Relief | 50 min. | 1.91 score on a scale | Standard Deviation 1.356 |
| Ibuprofen Caplets | Headache Relief | 180 min. | 3.59 score on a scale | Standard Deviation 0.907 |
| Ibuprofen Caplets | Headache Relief | 25 min. | 0.77 score on a scale | Standard Deviation 0.87 |
| Ibuprofen Caplets | Headache Relief | 40 min. | 1.62 score on a scale | Standard Deviation 1.195 |
| Ibuprofen Caplets | Headache Relief | 240 min. | 3.55 score on a scale | Standard Deviation 1.138 |
| Ibuprofen Caplets | Headache Relief | 60 min. | 2.34 score on a scale | Standard Deviation 1.255 |
| Placebo Caplets | Headache Relief | 240 min. | 3.32 score on a scale | Standard Deviation 1.155 |
| Placebo Caplets | Headache Relief | 10 min. | 0.11 score on a scale | Standard Deviation 0.379 |
| Placebo Caplets | Headache Relief | 20 min. | 0.60 score on a scale | Standard Deviation 0.876 |
| Placebo Caplets | Headache Relief | 25 min. | 0.88 score on a scale | Standard Deviation 0.986 |
| Placebo Caplets | Headache Relief | 30 min. | 1.22 score on a scale | Standard Deviation 1.107 |
| Placebo Caplets | Headache Relief | 40 min. | 1.49 score on a scale | Standard Deviation 1.182 |
| Placebo Caplets | Headache Relief | 50 min. | 1.82 score on a scale | Standard Deviation 1.218 |
| Placebo Caplets | Headache Relief | 60 min. | 2.14 score on a scale | Standard Deviation 1.213 |
| Placebo Caplets | Headache Relief | 90 min. | 2.68 score on a scale | Standard Deviation 1.196 |
| Placebo Caplets | Headache Relief | 120 min. | 3.03 score on a scale | Standard Deviation 1.206 |
| Placebo Caplets | Headache Relief | 180 min. | 3.44 score on a scale | Standard Deviation 0.978 |
| Placebo Caplets | Headache Relief | 15 min. | 0.27 score on a scale | Standard Deviation 0.635 |
Secondary
Number of Pain Free Participants
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paracetamol/ Caffeine Caplets | Number of Pain Free Participants | At 1 hour | 18 number of participants |
| Paracetamol/ Caffeine Caplets | Number of Pain Free Participants | At 2 hour | 38 number of participants |
| Ibuprofen Caplets | Number of Pain Free Participants | At 1 hour | 17 number of participants |
| Ibuprofen Caplets | Number of Pain Free Participants | At 2 hour | 41 number of participants |
| Placebo Caplets | Number of Pain Free Participants | At 2 hour | 20 number of participants |
| Placebo Caplets | Number of Pain Free Participants | At 1 hour | 6 number of participants |
Secondary
Number of Participants With Meaningful Pain Relief
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paracetamol/ Caffeine Caplets | Number of Participants With Meaningful Pain Relief | number of participants | 61 number of participants |
| Paracetamol/ Caffeine Caplets | Number of Participants With Meaningful Pain Relief | number of censored participants | 1 number of participants |
| Ibuprofen Caplets | Number of Participants With Meaningful Pain Relief | number of censored participants | 2 number of participants |
| Ibuprofen Caplets | Number of Participants With Meaningful Pain Relief | number of participants | 60 number of participants |
| Placebo Caplets | Number of Participants With Meaningful Pain Relief | number of censored participants | 1 number of participants |
| Placebo Caplets | Number of Participants With Meaningful Pain Relief | number of participants | 32 number of participants |
Secondary
Number of Participants With Perceptible Pain Relief
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paracetamol/ Caffeine Caplets | Number of Participants With Perceptible Pain Relief | number of participants | 62 number of participants |
| Paracetamol/ Caffeine Caplets | Number of Participants With Perceptible Pain Relief | number of censored participants | 0 number of participants |
| Ibuprofen Caplets | Number of Participants With Perceptible Pain Relief | number of participants | 61 number of participants |
| Ibuprofen Caplets | Number of Participants With Perceptible Pain Relief | number of censored participants | 1 number of participants |
| Placebo Caplets | Number of Participants With Perceptible Pain Relief | number of participants | 33 number of participants |
| Placebo Caplets | Number of Participants With Perceptible Pain Relief | number of censored participants | 0 number of participants |
Secondary
Rate of Rescue Medication
Number of participants that took rescue medication over the total number of participants for a given treatment group
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paracetamol/ Caffeine Caplets | Rate of Rescue Medication | 2 number of participants |
| Ibuprofen Caplets | Rate of Rescue Medication | 4 number of participants |
| Placebo Caplets | Rate of Rescue Medication | 4 number of participants |
Secondary
Sum of Pain Intensity Difference (SPID) at 1, 2 and 3 Hours
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paracetamol/ Caffeine Caplets | 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 |
| Paracetamol/ Caffeine Caplets | 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 |
| Paracetamol/ Caffeine Caplets | 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 |
| Ibuprofen Caplets | Sum of Pain Intensity Difference (SPID) at 1, 2 and 3 Hours | At 1 hour (n=62, 61, 33) | -0.56 score on a scale | Standard Deviation 0.418 |
| Ibuprofen Caplets | Sum of Pain Intensity Difference (SPID) at 1, 2 and 3 Hours | At 2 hour (n=62, 61, 33) | -2.02 score on a scale | Standard Deviation 1.002 |
| Ibuprofen Caplets | Sum of Pain Intensity Difference (SPID) at 1, 2 and 3 Hours | At 3 hour (n=61, 62, 32) | -3.86 score on a scale | Standard Deviation 1.342 |
| Placebo Caplets | Sum of Pain Intensity Difference (SPID) at 1, 2 and 3 Hours | At 1 hour (n=62, 61, 33) | -0.57 score on a scale | Standard Deviation 0.505 |
| Placebo Caplets | Sum of Pain Intensity Difference (SPID) at 1, 2 and 3 Hours | At 3 hour (n=61, 62, 32) | -3.97 score on a scale | Standard Deviation 1.528 |
| Placebo Caplets | Sum of Pain Intensity Difference (SPID) at 1, 2 and 3 Hours | At 2 hour (n=62, 61, 33) | -2.04 score on a scale | Standard Deviation 1.088 |
Secondary
Time to Meaningful Headache Relief
Time to meaningful headache relief was assessed as time when participants reported a PRS ≥ 2.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Paracetamol/ Caffeine Caplets | Time to Meaningful Headache Relief | 43.33 min. | Full Range 49.342 |
| Ibuprofen Caplets | Time to Meaningful Headache Relief | 54.17 min. | Full Range 49.095 |
| Placebo Caplets | Time to Meaningful Headache Relief | 46.67 min. | Full Range 61.477 |
Secondary
Time to Perceptible Headache Relief
Time to perceptible headache relief was assessed as the time when participants achieve pain relief scores (PRS) more than or equal to 1.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Paracetamol/ Caffeine Caplets | Time to Perceptible Headache Relief | 27.00 minutes (min.) | Full Range 31.274 |
| Ibuprofen Caplets | Time to Perceptible Headache Relief | 29.67 minutes (min.) | Full Range 41.173 |
| Placebo Caplets | Time to Perceptible Headache Relief | 27.00 minutes (min.) | Full Range 38.042 |
Secondary
Time to the Use of Rescue Medication.
Time taken by the participants to use the rescue medication
Time frame: Up to 4 hours
Population: ITT population defined as all participants who received treatment and who had at least one post-baseline efficacy assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paracetamol/ Caffeine Caplets | Time to the Use of Rescue Medication. | 239.00 Minutes | Standard Deviation 6.86 |
| Ibuprofen Caplets | Time to the Use of Rescue Medication. | 235.14 Minutes | Standard Deviation 24.06 |
| Placebo Caplets | Time to the Use of Rescue Medication. | 235.55 Minutes | Standard Deviation 12.8 |
Secondary
Total Pain Relief (TOTPAR)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paracetamol/ Caffeine Caplets | Total Pain Relief (TOTPAR) | Baseline-3 hour (61, 62, 33) | 7.84 score on a scale | Standard Deviation 2.337 |
| Paracetamol/ Caffeine Caplets | Total Pain Relief (TOTPAR) | Baseline-1 hour (62, 61, 33) | 1.31 score on a scale | Standard Deviation 0.922 |
| Paracetamol/ Caffeine Caplets | Total Pain Relief (TOTPAR) | Baseline-4 hour (59, 59, 33) | 11.57 score on a scale | Standard Deviation 3.373 |
| Paracetamol/ Caffeine Caplets | Total Pain Relief (TOTPAR) | Baseline-2 hour (62, 61, 33) | 4.28 score on a scale | Standard Deviation 1.818 |
| Ibuprofen Caplets | Total Pain Relief (TOTPAR) | Baseline-3 hour (61, 62, 33) | 7.51 score on a scale | Standard Deviation 2.25 |
| Ibuprofen Caplets | Total Pain Relief (TOTPAR) | Baseline-2 hour (62, 61, 33) | 4.05 score on a scale | Standard Deviation 1.74 |
| Ibuprofen Caplets | Total Pain Relief (TOTPAR) | Baseline-1 hour (62, 61, 33) | 1.17 score on a scale | Standard Deviation 0.801 |
| Ibuprofen Caplets | Total Pain Relief (TOTPAR) | Baseline-4 hour (59, 59, 33) | 11.05 score on a scale | Standard Deviation 3.774 |
| Placebo Caplets | Total Pain Relief (TOTPAR) | Baseline-2 hour (62, 61, 33) | 3.82 score on a scale | Standard Deviation 1.886 |
| Placebo Caplets | Total Pain Relief (TOTPAR) | Baseline-1 hour (62, 61, 33) | 1.14 score on a scale | Standard Deviation 0.864 |
| Placebo Caplets | Total Pain Relief (TOTPAR) | Baseline-4 hour (59, 59, 33) | 10.47 score on a scale | Standard Deviation 4.053 |
| Placebo Caplets | Total Pain Relief (TOTPAR) | Baseline-3 hour (61, 62, 33) | 7.35 score on a scale | Standard Deviation 2.463 |