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

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

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).

Study Overview

• Status: Terminated
• Conditions: Pain
• Intervention / Treatment: Drug: Paracetamol and Caffeine; Drug: Ibuprofen; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 365
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Waltham, Massachusetts, United States, 02451
      • Parexel International, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Paracetamol/ Caffeine Caplets; Two caplets of paracetamol/caffeine combination plus 2 placebo caplets to be administered	Drug: Paracetamol and Caffeine; Caplets containing 500 milligrams (mg) of paracetamol and 65 mg of caffeine
ACTIVE_COMPARATOR: Ibuprofen Caplets; Two ibuprofen caplets plus two placebo caplets to be administered	Drug: Ibuprofen; Caplets containing 200 mg of ibuprofen
PLACEBO_COMPARATOR: Placebo Caplets; Four placebo caplets to be administered	Other: Placebo; Matching placebo caplets

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2013
• Primary Completion (ACTUAL): March 31, 2015
• Study Completion (ACTUAL): March 31, 2015

Study Registration Dates

• First Submitted: April 25, 2013
• First Submitted That Met QC Criteria: April 25, 2013
• First Posted (ESTIMATE): April 29, 2013

Study Record Updates

• Last Update Posted (ACTUAL): September 1, 2017
• Last Update Submitted That Met QC Criteria: August 2, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; 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: 202172; RH01649 (OTHER: GSK)