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

Study Overview
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Brief Summary
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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).

Official Title
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A Study to Assess Efficacy Over Placebo and Speed of Onset of Pain Relief of New Paracetamol and Caffeine Tablets as Compared to Ibuprofen in Episodic Tension Type Headache

Conditions
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Pain

Intervention / Treatment
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* Drug: Paracetamol and Caffeine
* Drug: Ibuprofen
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants in good general health, and with diagnosis of ETTH with following conditions: number of days with the condition is historically greater than or equal to two per month; severity of headaches is historically at least moderate; 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paracetamol/ Caffeine Caplets<br>Two caplets of paracetamol/caffeine combination plus 2 placebo caplets to be administered | Drug: Paracetamol and Caffeine<br>* Caplets containing 500 milligrams (mg) of paracetamol and 65 mg of caffeine<br>|
| Active Comparator: Ibuprofen Caplets<br>Two ibuprofen caplets plus two placebo caplets to be administered | Drug: Ibuprofen<br>* Caplets containing 200 mg of ibuprofen<br>|
| Placebo Comparator: Placebo Caplets<br>Four placebo caplets to be administered | Other: Placebo<br>* Matching placebo caplets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Up to 4 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | From (Baseline) 0 to 1 hour, 0 to 2 hours, and 0 to 3 hours post dose | 
| Number of Participants With Perceptible Pain Relief |  | Baseline up to 4 hours | 
| 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. | Baseline up to 4 hours | 
| Number of Participants With Meaningful Pain Relief |  | Baseline up to 4 hours | 
| Time to Meaningful Headache Relief | Time to meaningful headache relief was assessed as time when participants reported a PRS ≥ 2. | Baseline up to 4 hours | 
| 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. | From (Baseline) 0 to 1, from 0 to 2, from 0 to 3 and from 0 to 4 hour post dose | 
| 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. | From (Baseline) 0 to 1 hour, 0 to 2 hours, 0 to 3 hours and 0 to 4 hours post dose | 
| 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). | 4 hours | 
| Rate of Rescue Medication | Number of participants that took rescue medication over the total number of participants for a given treatment group | 4 hours | 
| 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). | At 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 180, and 240 min. | 
| 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. | 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., | 
| 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. | 1 hour and 2 hour post dose | 
| Time to the Use of Rescue Medication. | Time taken by the participants to use the rescue medication | Up to 4 hours |