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

• ClinicalTrials.gov Identifier: NCT01842633
• Recruitment Status: Terminated
• First Posted: April 29, 2013
• Results First Posted: July 27, 2017
• Last Update Posted: September 1, 2017
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Pain	Drug: Paracetamol and Caffeine; Drug: Ibuprofen; Other: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 365 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: April 1, 2013
• Actual Primary Completion Date: March 31, 2015
• Actual Study Completion Date: March 31, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Sum of Pain Intensity Difference (SPID) of Treatment and Placebo at 4 Hours [ Time Frame: 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 Outcome Measures :

1. Sum of Pain Intensity Difference (SPID) at 1, 2 and 3 Hours [ Time Frame: 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).

2. Number of Participants With Perceptible Pain Relief [ Time Frame: Baseline up to 4 hours ]
3. Time to Perceptible Headache Relief [ Time Frame: 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.
4. Number of Participants With Meaningful Pain Relief [ Time Frame: Baseline up to 4 hours ]
5. Time to Meaningful Headache Relief [ Time Frame: Baseline up to 4 hours ]
   Time to meaningful headache relief was assessed as time when participants reported a PRS ≥ 2.
6. Total Pain Relief (TOTPAR) [ Time Frame: 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.
7. Area Under the Time-Response Curve for Change in Headache Intensity and Headache Relief (SPRID) [ Time Frame: 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.
8. Global Evaluation of Response to Treatment [ Time Frame: 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).
9. Rate of Rescue Medication [ Time Frame: 4 hours ]
   Number of participants that took rescue medication over the total number of participants for a given treatment group
10. Change From Baseline in Headache Pain Intensity [ Time Frame: 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).
11. Headache Relief [ 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., ]
    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.
12. Number of Pain Free Participants [ Time Frame: 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.
13. Time to the Use of Rescue Medication. [ Time Frame: Up to 4 hours ]
    Time taken by the participants to use the rescue medication

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Massachusetts

PAREXEL International, LLC

Waltham, Massachusetts, United States, 02451

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01842633
• Other Study ID Numbers: 202172; RH01649 ( Other Identifier: GSK )
• First Posted: April 29, 2013
• Results First Posted: July 27, 2017
• Last Update Posted: September 1, 2017
• Last Verified: August 2017

Additional relevant MeSH terms:

Headache; Pain; Neurologic Manifestations; Acetaminophen; Ibuprofen; Caffeine; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antipyretics; Central Nervous System Stimulants; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neurotransmitter Agents