Paracetamol With Caffeine to Treat Episodic Tension Type Headache

Study Overview
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Brief Summary
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This study will compare a fast-absorbing paracetamol plus caffeine formula with placebo and an over-the-counter dose of paracetamol and ibuprofen to treat episodic tension headache.

Official Title
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A Study to Assess the Efficacy of Paracetamol Taken in Combination With Caffeine for the Treatment of Episodic Tension Type Headache

Conditions
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Headache, Tension-Type

Intervention / Treatment
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* Drug: Placebo
* Drug: Experimental paracetamol + caffeine formulation
* Drug: ibuprofen marketed formulation
* Drug: Paracetamol marketed formulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of episodic tension-type headache consistent with all of the following: number of days with the condition is historically greater than or equal to two per month onset of condition was greater than or equal to 12 months from Visit 1 age of onset was < 50 years severity of headaches is historically at least moderate duration of headaches is historically greater than or equal to four hours, if untreated number of headache episodes was greater than or equal to 4 and less than or equal to 10 during each of the three months immediately prior to Visit 1 treatment of headache episodes with OTC analgesics has historically provided pain relief in less than or equal to 2 hours Exclusion Criteria: Subject has chronic tension type headache, which is defined as headache on more than 15 days per month for 3 months. If a migraine sufferer,subject averages more than one episode per month, is incapable of differentiating between tension-type headaches and migraine headaches, and/or requires regular or prophylactic use of migraine medications

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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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Arm 1<br>Placebo | Drug: Placebo<br>* Placebo<br>|
| Active Comparator: Arm 2<br>paracetamol marketed forumulation | Drug: Paracetamol marketed formulation<br>* Paracetamol marketed formulation<br>|
| Active Comparator: Arm 3<br>ibuprofen marketed formulation | Drug: ibuprofen marketed formulation<br>* ibuprofen marketed formulation<br>|
| Experimental: Arm 4<br>experimental paracetamol + caffeine formulation | Drug: Experimental paracetamol + caffeine formulation<br>* experimental paracetamol + caffeine formulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Perceptible Headache Relief | Time to first perceptible pain relief, calculated as time when partcipant selected 'a little' pain relief in the electronic pad minus the time of treatment. If this time was not available in the electronic pad then the earliest time corresponding to a pain relief score 1 or greater was recorded as time to 'a little' pain relief. | Baseline to 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Headache Severity | Headache severity (scores) at 15, 30, 45, 60, 90, 120, and 240 minutes were calculated as change (difference) from baseline of pain intensity at each time point. Pain intensity was measured by numerical rating scale which is a horizontal line with a scale from 0-10, where 0 represents no pain and 10 represents the worst possible pain. | Baseline to 4 hours | 
| Patients Global Assessment in Response to Treatment | Patients Global Assessment in Response to Treatment was assessed by a score in a scale from 0-4: 0- Poor; 1- Fair; 2- Good; 3- Very Good and 4- Excellent. | Baseline to 8 weeks | 
| Headache Relief Scores | Pain relief scores were measured on a scale from 0-4: 0- No pain relief; 1- Perceptible pain relief; 2- Meaningful pain relief; 3- A lot of relief and 4- Complete relief. | Baseline to 4 hours | 
| Total Pain Relief (TOTPAR) | TOTPAR was calculated as sum of the products of pain relief score at time interval at 0-60 minutes, 60-90 minutes, 90-120 minutes and 120-240 minutes. Participants were asked to choose a number on a scale of 0 to 4, where, 0- No pain relief; 1- A little or perceptible pain relief; 2- Meaningful pain relief; 3- A lot of relief; 4- Complete relief. The mean PRS scores were calculated on the basis of participant's response based on the above score. It was calculated using the following formula. TOTPAR t = Σ(Rt x (time t - time t-1)), where Rt = pain relief score at time t; time t = time t in hours; time t-1 = time at previous time-point. | Baseline to 4 hours | 
| Sum of Pain Intensity Difference (SPID) | Sum of pain intensity difference (SPID) at 60, 90, 120 and 240 minutes - calculated as the sum of headache intensity differences between the baseline pain intensity score and pain intensity score at each timepoint. Pain intensity was measured by numerical rating scale which is horizontal line with a scale from 0-10, where 0 represents no pain and 10 represents the worst possible pain. It was calculated using the following formula; SPID t = ΣPID x (time t - time t-1), where PID = PI (baseline) - PI t and PI = pain intensity. | Baseline to 4 hours | 
| Sum of TOTPAR and SPID (SPRID) | Area under the time-response curve for change in headache intensity and headache relief (SPRID) at 60, 90, 120 and 240 minutes, was calculated as sum of TOTPAR and SPID: SPRIDt = TOTPARt + SPIDt TOTPAR was calculated as sum of the products of pain relief score. Participants were asked to choose a number on a scale of 0 to 4, where, 0- No pain relief; 1- A little or perceptible pain relief; 2- Meaningful pain relief; 3- A lot of relief; 4- Complete relief. The mean PRS scores were calculated on the basis of participant's response based on the above score. SPID was calculated as the sum of headache intensity differences between baseline and at each time point. It was measured by numerical rating scale which is horizontal line with a scale from 0-10, where 0 represents no pain and 10 represents the worst possible pain. | Baseline to 4 hours | 
| Time to Rescue Medication | Time to rescue medication was evaluated. | Baseline to 6 hours post dose | 
| Number of Participants With Complete Headache Relief | Number of headaches resolved at 1 and 2 hours before any rescue medication was calculated as number of participants with complete pain relief and headache severity of 'no headache' over total number of participants. These calculations were based on one headache per treatment per subject. | Baseline to 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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caffeine, paracetamol, tension headache