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

Tracking Information

• First Submitted Date: April 25, 2013
• First Posted Date: April 29, 2013
• Results First Submitted Date: June 2, 2016
• Results First Posted Date: July 27, 2017
• Last Update Posted Date: September 1, 2017
• Actual Study Start Date: April 1, 2013
• Actual Primary Completion Date: March 31, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 28, 2017)

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).

Original Primary Outcome Measures (submitted: April 25, 2013)

Sum of pain intensity difference (SPID) of experimental formulation vs placebo [ Time Frame: Baseline to 4 hours post dose ]

SPID to be calculated as the sum of headache intensity differences at 4 hours post-dose. Pain intensity at each time point will be calculated as difference of pain intensity at baseline with pain intensity at a given time point.

Current Secondary Outcome Measures (submitted: June 28, 2017)

• 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).
• Number of Participants With Perceptible Pain Relief [ Time Frame: Baseline up to 4 hours ]
• 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.
• Number of Participants With Meaningful Pain Relief [ Time Frame: Baseline up to 4 hours ]
• 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.
• 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.
• 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.
• 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).
• 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
• 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).
• 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.
• 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.
• Time to the Use of Rescue Medication. [ Time Frame: Up to 4 hours ]
  Time taken by the participants to use the rescue medication

Original Secondary Outcome Measures (submitted: April 25, 2013)

• SPID of other treatments [ Time Frame: Baseline, 1, 2, 3 and 4 hours post dose ]
  Pain intensity at each time point will be calculated as difference of pain intensity at baseline with pain intensity at a given time point.
• Time to perceptible headache relief [ Time Frame: Baseline to 4 hours ]
  This endpoint will be assessed as time when participants achieve pain relief scores (PRS) more than or equal to 1.
• Time to meaningful headache relief [ Time Frame: Baseline to 4 hours ]
  This endpoint will be assessed as time when subjects reported a PRS ≥ 2.
• Total pain relief (TOTPAR) [ Time Frame: 1, 2, 3 and 4 hour post dose ]
  TOTPAR will be sum of products of PRS at each time point with time interval between any two time points being used.
• Sum of TOTPAR and SPID (SPRID) [ Time Frame: 1, 2, 3 and 4 hour post dose ]
  Area under the time-response curve for change in headache intensity and headache relief.
• Global Evaluation of Response to Treatment [ Time Frame: 4 hours ]
  Global evaluation of treatment response is to be 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).
• Rate of rescue medication [ Time Frame: 4 hours ]
  Proportion of subjects that took rescue medication over the total number of subjects for a given treatment group.
• Time to rescue medication [ Time Frame: 4 hours ]
  Median time taken by participants who will opt for rescue medication to be determined.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Clinical Study to Evaluate Efficacy of New Paracetamol Formulation Compared to Ibuprofen in Headache
• 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
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Pain

Intervention

• Drug: Paracetamol and Caffeine
  Caplets containing 500 milligrams (mg) of paracetamol and 65 mg of caffeine
• Drug: Ibuprofen
  Caplets containing 200 mg of ibuprofen
• Other: Placebo
  Matching placebo caplets

Study Arms

• Experimental: Paracetamol/ Caffeine Caplets
  Two caplets of paracetamol/caffeine combination plus 2 placebo caplets to be administered
  Intervention: Drug: Paracetamol and Caffeine
• Active Comparator: Ibuprofen Caplets
  Two ibuprofen caplets plus two placebo caplets to be administered
  Intervention: Drug: Ibuprofen
• Placebo Comparator: Placebo Caplets
  Four placebo caplets to be administered
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: April 11, 2016): 365
• Original Estimated Enrollment (submitted: April 25, 2013): 300
• Actual Study Completion Date: March 31, 2015
• Actual Primary Completion Date: March 31, 2015 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01842633
• Other Study ID Numbers: 202172; RH01649 ( Other Identifier: GSK )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: GlaxoSmithKline
• Original Responsible Party: Same as current
• Current Study Sponsor: GlaxoSmithKline
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

• PRS Account: GlaxoSmithKline
• Verification Date: August 2017