Paracetamol With Caffeine to Treat Episodic Tension Type Headache

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

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.

Study Overview

• Status: Terminated
• Conditions: Headache, Tension-Type
• Intervention / Treatment: Drug: Placebo; Drug: Paracetamol marketed formulation; Drug: ibuprofen marketed formulation; Drug: Experimental paracetamol + caffeine formulation

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Pembroke Pines, Florida, United States, 33024
      • University Clinical Research, Inc.
  • Massachusetts
    • Springfield, Massachusetts, United States, 01104
      • Springfield Neurology Associates
    • Wellesley Hills, Massachusetts, United States, 02481
      • MedVadis Research Corporation
  • New York
    • Lake Success, New York, United States, 11042
      • Biomedical Research Alliance of New York LLC
    • Mount Vernon, New York, United States, 10550
      • Elkind Headache Center
    • Port Chester, New York, United States, 10573
      • International Research Service, Inc.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Jefferson Headache Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of episodic tension-type headache consistent with all of the following:

  1. number of days with the condition is historically greater than or equal to two per month
  2. onset of condition was greater than or equal to 12 months from Visit 1
  3. age of onset was < 50 years
  4. severity of headaches is historically at least moderate
  5. duration of headaches is historically greater than or equal to four hours, if untreated
  6. 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
  7. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Arm 1; Placebo	Drug: Placebo; Placebo
Active Comparator: Arm 2; paracetamol marketed forumulation	Drug: Paracetamol marketed formulation; Paracetamol marketed formulation
Active Comparator: Arm 3; ibuprofen marketed formulation	Drug: ibuprofen marketed formulation; ibuprofen marketed formulation
Experimental: Arm 4; experimental paracetamol + caffeine formulation	Drug: Experimental paracetamol + caffeine formulation; experimental paracetamol + caffeine formulation

What is the study measuring?

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 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
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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: June 23, 2011
• First Submitted That Met QC Criteria: December 19, 2012
• First Posted (Estimate): December 24, 2012

Study Record Updates

• Last Update Posted (Estimate): March 27, 2015
• Last Update Submitted That Met QC Criteria: March 12, 2015
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: caffeine; paracetamol; tension headache
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders, Primary; Headache Disorders; Headache; Tension-Type Headache; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Purinergic Antagonists; Purinergic Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Acetaminophen; Ibuprofen; Caffeine
• Other Study ID Numbers: A2260597