Study Evaluating A Novel Ibuprofen Formulation In Episodic Tension-Type Headache

Evaluation Of The Efficacy Of A Novel Ibuprofen Formulation In The Treatment Of Episodic Tension-Type Headache

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01077973

Enrollment

200

Registered

2010-03-01

Start date

2010-03-31

Completion date

2010-10-31

Last updated

2012-08-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pain

Keywords

Headache

Brief summary

This study will compare the ability of a single-dose of a novel ibuprofen formulation to relieve pain compared to placebo and standard ibuprofen in the treatment of episodic tension-type headache.

Interventions

DRUGNovel Ibuprofen

Single-dose of novel ibuprofen (equal to 400 mg ibuprofen) plus placebo

DRUGStandard Ibuprofen

Single-dose of standard ibuprofen (400mg) plus placebo

DRUGPlacebo

Single-dose of placebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

* Males and females at least 18 years to 65 years of age * A diagnosis of an episodic tension-type headache, as defined by the International Headache Society * A history of episodic tension-type headache with the following characteristics: 4 headache episodes per month for the last 6 months of moderately severe intensity; headache generally lasts more than 3 hours if left untreated; adequate headache relief is generally obtained with over-the-counter (OTC) doses of OTC analgesics

Exclusion criteria

* Pregnancy or breast-feeding * Alcohol or substance abuse * Any serious medical or psychiatric disorder * History of stomach ulcers, stomach bleed, or other bleeding disorders

Design outcomes

Primary

Measure	Time frame	Description
Time-weighted Sum of Pain Relief Rating and Pain Intensity Difference From 0-3 Hours (SPRID 0-3) for Ibuprofen Sodium Versus Placebo Tablet	0 to 3 hours	SPRID:time-weighted sum of pain relief rating combined with pain intensity difference (PRID) over 3 hours. SPRID score range:-3 (worst) to 21 (best) for SPRID 0-3. PRID: sum of pain intensity differences (PID) and pain relief rating(PRR) at each time point. PRID score range: -1=worst to 7=best. PID: baseline pain severity score minus pain severity score at a given time point (score range 0=none to 3=severe; baseline score range 2=moderately severe to 3=severe). Total score range for PID: -1(worst) to 3 (best). PRR:assessed on 5-point pain relief rating scale (0=No relief to 4=Complete relief).
Time to Onset of Meaningful Relief for Ibuprofen Sodium Versus Ibuprofen (Motrin IB) Tablet	0 to 3 hours	Participants evaluated the time to meaningful relief by stopping a second stopwatch labeled 'meaningful relief' at the moment the participant first began to experience meaningful relief. It was also considered achieved if the participant stated meaningful relief at the time the first stopwatch was depressed. Stopwatch was active up to 3 hours after dosing or until stopped by the participant, or rescue medication was administered.

Secondary

Measure	Time frame	Description
Pain Relief Rating (PRR)	1, 2, 3 hours	PRR was assessed on a 5-point categorical pain relief rating scale wherein 0=No relief to 4=Complete relief.
Pain Intensity Difference (PID)	1, 2, 3 hours	PID was derived by subtracting the pain severity score at a given post-dosing time point \[pain severity score range 0 (none) to 3 (severe)\] from the baseline score \[Baseline pain severity score range 2 (moderately severe) to 3 (severe)\]. Total possible score range for PID: -1 (worst) to 3 (best).
Sum of Pain Relief Rating and Pain Intensity Difference (PRID)	1, 2, 3 hours	PRID was sum of PID and PRR at each post-dosing time point. The overall possible score range, for PRID was -1 (worst) to 7 (best). PID was derived by subtracting the pain severity score at a given post-dosing time point \[pain severity score range 0 (none) to 3 (severe)\] from the baseline score \[Baseline pain severity score range 2 (moderately severe) to 3 (severe)\]. Total possible score range for PID: -1 (worst) to 3 (best). PRR was assessed on 5-point categorical pain relief rating scale (0=No relief to 4=Complete relief).
Time-weighted Sum of Pain Intensity Difference (SPID)	0 to 2, 0 to 3 hours	SPID: time-weighted sum of PID over 2 and 3 hours. SPID score range was -2(worst) to 6 (best) for SPID 0-2 and -3 (worst) to 9 (best) for SPID 0-3. PID: baseline pain severity score minus pain severity score at a given time point (score range 0=none to 3=severe; baseline score range 2=moderately severe to 3=severe). Total score range for PID: -1(worst) to 3 (best).
Time-weighted Sum of Pain Relief Rating (TOTPAR)	0 to 2, 0 to 3 hours	TOTPAR: time-weighted sum of PRR over 2 and 3 hours. TOTPAR score range was 0 (worst) to 8 (best) for TOTPAR 0-2 and 0 (worst) to 12 (best) for TOTPAR 0-3. PRR was assessed on a 5-point categorical pain relief rating scale wherein 0=No relief to 4=Complete relief.
Time to Onset of Meaningful Relief: Remaining Comparisons	0 to 3 hours	Participants evaluated the time to meaningful relief by stopping a second stopwatch labeled 'meaningful relief' at the moment the participant first began to experience meaningful relief. It was also considered achieved if the participant stated meaningful relief at the time the first stopwatch was depressed. Stopwatch was active up to 3 hours after dosing or until stopped by the participant, or rescue medication was administered.
Cumulative Percentage of Participants With Meaningful Relief	0.5, 1, 2, 3 hours	Percentage of participants with meaningful relief evaluated by stopping a second stopwatch labeled 'meaningful relief' at the moment the participant first began to experience meaningful relief. It was also considered achieved if the participant stated meaningful relief at the time the first stopwatch was depressed. Stopwatch was active up to 3 hours after dosing or until stopped by the participant, or rescue medication was administered.
Cumulative Percentage of Participants With Confirmed First Perceptible Relief	0.5, 1, 2, 3 hours	Percentage of participants with first perceptible relief evaluated by stopping a stopwatch labeled 'first perceptible relief' at the moment the participant first began to experience any relief. Stopwatch was active up to 3 hours after dosing or until stopped by the participant, or rescue medication was administered. First perceptible relief was considered confirmed by meaningful relief if the participant achieved both first perceptible and meaningful relief by either depressing the second stopwatch or by indicating that his/her first perceptible relief was also meaningful.
Time to Treatment Failure	0 to 3 hours	Median time of dropping out of the participants from the study due to lack of efficacy or received rescue medication, whichever came first.
Cumulative Percentage of Participants With Treatment Failure	0 to 3 hours	Percentage of participants who withdrew from the study due to lack of efficacy or received rescue medication.
Cumulative Percentage of Participants With Complete Relief	1, 2, 3 hours	Complete relief was defined as a PRR of 4. PRR was assessed on a 5-point categorical pain relief rating scale where 0=No relief to 4=Complete relief.
Time-weighted Sum of Pain Relief Rating and Pain Intensity Difference (SPRID)	0 to 2, 0 to 3 hours	SPRID: time-weighted sum of PRID over 2 and 3 hours. SPRID score range was -2(worst) to 14(best) for SPRID 0-2 and -3 (worst) to 21 (best) for SPRID 0-3. PRID: sum of PID and PRR at each time point. Total score range for PRID: -1=worst to 7=best. PID: baseline pain severity score minus pain severity score at a given time point (score range 0=none to 3=severe; baseline score range 2=moderately severe to 3=severe). Total score range for PID: -1(worst) to 3(best), PRR: assessed on 5-point pain relief rating scale (0=No relief to 4=Complete relief).
Time to Confirmed First Perceptible Relief	0 to 3 hours	Participants evaluated the time to first perceptible relief by stopping a stopwatch labeled 'first perceptible relief' at the moment the participant first began to experience any relief. Stopwatch was active up to 3 hours after dosing or until stopped by the participant, or rescue medication was administered. First perceptible relief was considered confirmed by meaningful relief if the participant achieved both first perceptible and meaningful relief by either depressing the second stopwatch or by indicating that his/her first perceptible relief was also meaningful.

Participant flow

Participants by arm

Arm	Count
Placebo Single oral dose of 2 placebo tablets matched to ibuprofen \[Motrin ibuprofen (IB)\] 200 milligram (mg) tablet along with single oral dose of 2 placebo tablets matched to ibuprofen sodium 256 mg tablet.	41
Ibuprofen Sodium Single oral dose of 2 ibuprofen sodium 256 mg tablets, equivalent to 400 mg ibuprofen along with single oral dose of 2 placebo tablets matched to ibuprofen (Motrin IB) 200 mg tablet.	79
Ibuprofen (Motrin IB) Single oral dose of 2 ibuprofen (Motrin IB) 200 mg tablets (total dose to 400 mg ibuprofen) along with single oral dose of 2 placebo tablets matched to ibuprofen sodium 256 mg tablet.	80
Total	200

Baseline characteristics

Characteristic	Total	Placebo	Ibuprofen Sodium	Ibuprofen (Motrin IB)
Age Continuous	42.3 Years STANDARD_DEVIATION 13.6	42.9 Years STANDARD_DEVIATION 13.5	43.4 Years STANDARD_DEVIATION 13.3	40.9 Years STANDARD_DEVIATION 14
Number of Participants with Pain Severity Score Moderately severe	147 Participants	30 Participants	58 Participants	59 Participants
Number of Participants with Pain Severity Score Severe	53 Participants	11 Participants	21 Participants	21 Participants
Sex: Female, Male Female	138 Participants	28 Participants	55 Participants	55 Participants
Sex: Female, Male Male	62 Participants	13 Participants	24 Participants	25 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	0 / 41	0 / 79	0 / 80
serious Total, serious adverse events	0 / 41	0 / 79	0 / 80

Outcome results

Primary

Time to Onset of Meaningful Relief for Ibuprofen Sodium Versus Ibuprofen (Motrin IB) Tablet

Participants evaluated the time to meaningful relief by stopping a second stopwatch labeled 'meaningful relief' at the moment the participant first began to experience meaningful relief. It was also considered achieved if the participant stated meaningful relief at the time the first stopwatch was depressed. Stopwatch was active up to 3 hours after dosing or until stopped by the participant, or rescue medication was administered.

Time frame: 0 to 3 hours

Population: ITT population included all randomized participants who received study medication and provided a baseline assessment.

Arm	Measure	Value (MEDIAN)
Placebo	Time to Onset of Meaningful Relief for Ibuprofen Sodium Versus Ibuprofen (Motrin IB) Tablet	50.3 Minutes
Ibuprofen Sodium	Time to Onset of Meaningful Relief for Ibuprofen Sodium Versus Ibuprofen (Motrin IB) Tablet	55.5 Minutes

Comparison: Hazard Ratio (HR) and corresponding 95% CI were calculated based on the Wald statistic from the proportional hazards (PH) model. Type I error was controlled at 0.05 significance level (2-sided) by stating pair wise comparisons significant only if overall treatment effect among 3 treatment groups was significant and testing in a sequential order Ibuprofen sodium vs. placebo for SPRID 0-3 then Ibuprofen sodium vs. Ibuprofen (Motrin IB) for time to meaningful relief.p-value: 0.19395% CI: [0.52, 1.14]Proportional hazards model

Primary

Time-weighted Sum of Pain Relief Rating and Pain Intensity Difference From 0-3 Hours (SPRID 0-3) for Ibuprofen Sodium Versus Placebo Tablet

SPRID:time-weighted sum of pain relief rating combined with pain intensity difference (PRID) over 3 hours. SPRID score range:-3 (worst) to 21 (best) for SPRID 0-3. PRID: sum of pain intensity differences (PID) and pain relief rating(PRR) at each time point. PRID score range: -1=worst to 7=best. PID: baseline pain severity score minus pain severity score at a given time point (score range 0=none to 3=severe; baseline score range 2=moderately severe to 3=severe). Total score range for PID: -1(worst) to 3 (best). PRR:assessed on 5-point pain relief rating scale (0=No relief to 4=Complete relief).

Time frame: 0 to 3 hours

Population: Intent-to-treat (ITT) population included all randomized participants who received study medication and provided a baseline assessment.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Time-weighted Sum of Pain Relief Rating and Pain Intensity Difference From 0-3 Hours (SPRID 0-3) for Ibuprofen Sodium Versus Placebo Tablet	11.2 Units on a scale	Standard Deviation 4.9
Ibuprofen Sodium	Time-weighted Sum of Pain Relief Rating and Pain Intensity Difference From 0-3 Hours (SPRID 0-3) for Ibuprofen Sodium Versus Placebo Tablet	10.8 Units on a scale	Standard Deviation 5.3

Comparison: Treatment difference (Ibuprofen sodium-placebo) and 95 percent (%) confidence interval (CI): based on LS means from analysis of variance (ANOVA). Type I error was controlled at 0.05 significance level (2-sided) by stating pair wise comparisons significant only if overall treatment effect among 3 treatment groups was significant and testing in a sequential order Ibuprofen sodium versus (vs.) placebo for SPRID 0-3 then Ibuprofen sodium vs. Ibuprofen (Motrin IB) for time to meaningful relief.p-value: 0.29995% CI: [-3.23, 1]ANOVA

Secondary

Cumulative Percentage of Participants With Complete Relief

Complete relief was defined as a PRR of 4. PRR was assessed on a 5-point categorical pain relief rating scale where 0=No relief to 4=Complete relief.

Time frame: 1, 2, 3 hours

Population: ITT population included all randomized participants who received study medication and provided a baseline assessment.

Arm	Measure	Group	Value (NUMBER)
Placebo	Cumulative Percentage of Participants With Complete Relief	2 hours	17.1 Percentage of participants
Placebo	Cumulative Percentage of Participants With Complete Relief	1 hour	2.4 Percentage of participants
Placebo	Cumulative Percentage of Participants With Complete Relief	3 hours	41.5 Percentage of participants
Ibuprofen Sodium	Cumulative Percentage of Participants With Complete Relief	2 hours	21.5 Percentage of participants
Ibuprofen Sodium	Cumulative Percentage of Participants With Complete Relief	1 hour	6.3 Percentage of participants
Ibuprofen Sodium	Cumulative Percentage of Participants With Complete Relief	3 hours	40.5 Percentage of participants
Ibuprofen (Motrin IB)	Cumulative Percentage of Participants With Complete Relief	1 hour	1.3 Percentage of participants
Ibuprofen (Motrin IB)	Cumulative Percentage of Participants With Complete Relief	3 hours	35.0 Percentage of participants
Ibuprofen (Motrin IB)	Cumulative Percentage of Participants With Complete Relief	2 hours	15.0 Percentage of participants

Comparison: 1 hour: Treatment difference (Ibuprofen sodium - placebo) and its associated 95% CI was calculated based on CMH adjusted proportions and the corresponding standard error.p-value: 0.35595% CI: [-3.33, 11.1]Cochran-Mantel-Haenszel

Comparison: 1 hour: Treatment difference \[Ibuprofen (Motrin IB) - placebo\] and its associated 95% CI was calculated based on CMH adjusted proportions and the corresponding standard error.p-value: 0.62395% CI: [-6.62, 4.2]Cochran-Mantel-Haenszel

Comparison: 1 hour: Treatment difference \[Ibuprofen sodium - Ibuprofen (Motrin IB)\] and its associated 95% CI was calculated based on CMH adjusted proportions and the corresponding standard error.p-value: 0.09495% CI: [-0.9, 11.11]Cochran-Mantel-Haenszel

Comparison: 2 hours: Treatment difference (Ibuprofen sodium - placebo) and its associated 95% CI was calculated based on CMH adjusted proportions and the corresponding standard error.p-value: 0.56595% CI: [-10.43, 19.29]Cochran-Mantel-Haenszel

Comparison: 2 hours: Treatment difference \[Ibuprofen (Motrin IB) - placebo\] and its associated 95% CI was calculated based on CMH adjusted proportions and the corresponding standard error.p-value: 0.76595% CI: [-16.15, 11.97]Cochran-Mantel-Haenszel

Comparison: 2 hours: Treatment difference \[Ibuprofen sodium - Ibuprofen (Motrin IB)\] and its associated 95% CI was calculated based on CMH adjusted proportions and the corresponding standard error.p-value: 0.28895% CI: [-5.43, 18.37]Cochran-Mantel-Haenszel

Comparison: 3 hours: Treatment difference (Ibuprofen sodium - placebo) and its associated 95% CI was calculated based on CMH adjusted proportions and the corresponding standard error.p-value: 0.92895% CI: [-20, 18.27]Cochran-Mantel-Haenszel

Comparison: 3 hours: Treatment difference \[Ibuprofen (Motrin IB) - placebo\] and its associated 95% CI was calculated based on CMH adjusted proportions and the corresponding standard error.p-value: 0.49595% CI: [-25.14, 12.33]Cochran-Mantel-Haenszel

Comparison: 3 hours: Treatment difference \[Ibuprofen sodium - Ibuprofen (Motrin IB)\] and its associated 95% CI was calculated based on CMH adjusted proportions and the corresponding standard error.p-value: 0.47795% CI: [-9.66, 20.59]Cochran-Mantel-Haenszel

Secondary

Cumulative Percentage of Participants With Confirmed First Perceptible Relief

Percentage of participants with first perceptible relief evaluated by stopping a stopwatch labeled 'first perceptible relief' at the moment the participant first began to experience any relief. Stopwatch was active up to 3 hours after dosing or until stopped by the participant, or rescue medication was administered. First perceptible relief was considered confirmed by meaningful relief if the participant achieved both first perceptible and meaningful relief by either depressing the second stopwatch or by indicating that his/her first perceptible relief was also meaningful.

Time frame: 0.5, 1, 2, 3 hours

Population: ITT population included all randomized participants who received study medication and provided a baseline assessment.

Arm	Measure	Group	Value (NUMBER)
Placebo	Cumulative Percentage of Participants With Confirmed First Perceptible Relief	0.5 hours	24.4 Percentage of participants
Placebo	Cumulative Percentage of Participants With Confirmed First Perceptible Relief	1 hour	80.5 Percentage of participants
Placebo	Cumulative Percentage of Participants With Confirmed First Perceptible Relief	2 hours	85.4 Percentage of participants
Placebo	Cumulative Percentage of Participants With Confirmed First Perceptible Relief	3 hours	85.4 Percentage of participants
Ibuprofen Sodium	Cumulative Percentage of Participants With Confirmed First Perceptible Relief	3 hours	81.0 Percentage of participants
Ibuprofen Sodium	Cumulative Percentage of Participants With Confirmed First Perceptible Relief	0.5 hours	30.4 Percentage of participants
Ibuprofen Sodium	Cumulative Percentage of Participants With Confirmed First Perceptible Relief	2 hours	81.0 Percentage of participants
Ibuprofen Sodium	Cumulative Percentage of Participants With Confirmed First Perceptible Relief	1 hour	67.1 Percentage of participants
Ibuprofen (Motrin IB)	Cumulative Percentage of Participants With Confirmed First Perceptible Relief	3 hours	82.5 Percentage of participants
Ibuprofen (Motrin IB)	Cumulative Percentage of Participants With Confirmed First Perceptible Relief	1 hour	72.5 Percentage of participants
Ibuprofen (Motrin IB)	Cumulative Percentage of Participants With Confirmed First Perceptible Relief	2 hours	82.5 Percentage of participants
Ibuprofen (Motrin IB)	Cumulative Percentage of Participants With Confirmed First Perceptible Relief	0.5 hours	28.8 Percentage of participants

Comparison: 0.5 hours: Treatment difference (Ibuprofen sodium - placebo) and its associated 95% CI was calculated based on CMH adjusted proportions and the corresponding standard error.p-value: 0.4895% CI: [-10.86, 22.99]Cochran-Mantel-Haenszel

Comparison: 0.5 hours: Treatment difference \[Ibuprofen (Motrin IB) - placebo\] and its associated 95% CI was calculated based on CMH adjusted proportions and the corresponding standard error.p-value: 0.61295% CI: [-12.55, 21.23]Cochran-Mantel-Haenszel

Comparison: 0.5 hours: Treatment difference \[Ibuprofen sodium - Ibuprofen (Motrin IB)\] and its associated 95% CI was calculated based on CMH adjusted proportions and the corresponding standard error.p-value: 0.83995% CI: [-12.6, 15.55]Cochran-Mantel-Haenszel

Secondary

Cumulative Percentage of Participants With Meaningful Relief

Percentage of participants with meaningful relief evaluated by stopping a second stopwatch labeled 'meaningful relief' at the moment the participant first began to experience meaningful relief. It was also considered achieved if the participant stated meaningful relief at the time the first stopwatch was depressed. Stopwatch was active up to 3 hours after dosing or until stopped by the participant, or rescue medication was administered.

Time frame: 0.5, 1, 2, 3 hours

Population: ITT population included all randomized participants who received study medication and provided a baseline assessment.

Arm	Measure	Group	Value (NUMBER)
Placebo	Cumulative Percentage of Participants With Meaningful Relief	0.5 hours	14.6 Percentage of participants
Placebo	Cumulative Percentage of Participants With Meaningful Relief	1 hour	65.9 Percentage of participants
Placebo	Cumulative Percentage of Participants With Meaningful Relief	2 hours	85.4 Percentage of participants
Placebo	Cumulative Percentage of Participants With Meaningful Relief	3 hours	85.4 Percentage of participants
Ibuprofen Sodium	Cumulative Percentage of Participants With Meaningful Relief	3 hours	81.0 Percentage of participants
Ibuprofen Sodium	Cumulative Percentage of Participants With Meaningful Relief	0.5 hours	17.7 Percentage of participants
Ibuprofen Sodium	Cumulative Percentage of Participants With Meaningful Relief	2 hours	79.7 Percentage of participants
Ibuprofen Sodium	Cumulative Percentage of Participants With Meaningful Relief	1 hour	58.2 Percentage of participants
Ibuprofen (Motrin IB)	Cumulative Percentage of Participants With Meaningful Relief	3 hours	82.5 Percentage of participants
Ibuprofen (Motrin IB)	Cumulative Percentage of Participants With Meaningful Relief	1 hour	60.0 Percentage of participants
Ibuprofen (Motrin IB)	Cumulative Percentage of Participants With Meaningful Relief	2 hours	81.3 Percentage of participants
Ibuprofen (Motrin IB)	Cumulative Percentage of Participants With Meaningful Relief	0.5 hours	10.0 Percentage of participants

Comparison: 0.5 hours: Treatment difference (Ibuprofen sodium - placebo) and its associated 95% CI was calculated based on Cochran-Mantel-Haenszel (CMH) adjusted proportions and the corresponding standard error.p-value: 0.67295% CI: [-11.03, 17.07]Cochran-Mantel-Haenszel

Secondary

Cumulative Percentage of Participants With Treatment Failure

Percentage of participants who withdrew from the study due to lack of efficacy or received rescue medication.

Time frame: 0 to 3 hours

Population: Data was not analyzed as there were no treatment failures observed and no participant received rescue medication in the study.

Secondary

Pain Intensity Difference (PID)

PID was derived by subtracting the pain severity score at a given post-dosing time point \[pain severity score range 0 (none) to 3 (severe)\] from the baseline score \[Baseline pain severity score range 2 (moderately severe) to 3 (severe)\]. Total possible score range for PID: -1 (worst) to 3 (best).

Time frame: 1, 2, 3 hours

Population: ITT population included all randomized participants who received study medication and provided a baseline assessment.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Pain Intensity Difference (PID)	2 hours	1.3 Units on a scale	Standard Deviation 0.7
Placebo	Pain Intensity Difference (PID)	1 hour	0.9 Units on a scale	Standard Deviation 0.6
Placebo	Pain Intensity Difference (PID)	3 hours	1.5 Units on a scale	Standard Deviation 0.8
Ibuprofen Sodium	Pain Intensity Difference (PID)	2 hours	1.3 Units on a scale	Standard Deviation 0.7
Ibuprofen Sodium	Pain Intensity Difference (PID)	1 hour	0.9 Units on a scale	Standard Deviation 0.6
Ibuprofen Sodium	Pain Intensity Difference (PID)	3 hours	1.5 Units on a scale	Standard Deviation 0.9
Ibuprofen (Motrin IB)	Pain Intensity Difference (PID)	1 hour	0.8 Units on a scale	Standard Deviation 0.6
Ibuprofen (Motrin IB)	Pain Intensity Difference (PID)	3 hours	1.4 Units on a scale	Standard Deviation 0.9
Ibuprofen (Motrin IB)	Pain Intensity Difference (PID)	2 hours	1.2 Units on a scale	Standard Deviation 0.8

Comparison: 1 hour: Treatment difference (Ibuprofen sodium - placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.38295% CI: [-0.36, 0.14]ANOVA

Comparison: 1 hour: Treatment difference \[Ibuprofen (Motrin IB) - placebo\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.24295% CI: [-0.39, 0.1]ANOVA

Comparison: 1 hour: Treatment difference \[Ibuprofen sodium - Ibuprofen (Motrin IB)\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.7295% CI: [-0.17, 0.24]ANOVA

Comparison: 2 hours: Treatment difference (Ibuprofen sodium - placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.23595% CI: [-0.43, 0.11]ANOVA

Comparison: 2 hours: Treatment difference \[Ibuprofen (Motrin IB) - placebo\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.6395% CI: [-0.34, 0.2]ANOVA

Comparison: 2 hours: Treatment difference \[Ibuprofen sodium - Ibuprofen (Motrin IB)\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.39395% CI: [-0.32, 0.13]ANOVA

Comparison: 3 hours: Treatment difference (Ibuprofen sodium - placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.38295% CI: [-0.46, 0.18]ANOVA

Comparison: 3 hours: Treatment difference \[Ibuprofen (Motrin IB) - placebo\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.99595% CI: [-0.32, 0.32]ANOVA

Comparison: 3 hours: Treatment difference \[Ibuprofen sodium - Ibuprofen (Motrin IB)\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.28795% CI: [-0.41, 0.12]ANOVA

Secondary

Pain Relief Rating (PRR)

PRR was assessed on a 5-point categorical pain relief rating scale wherein 0=No relief to 4=Complete relief.

Time frame: 1, 2, 3 hours

Population: ITT population included all randomized participants who received study medication and provided a baseline assessment.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Pain Relief Rating (PRR)	2 hours	2.6 Units on a scale	Standard Deviation 1.1
Placebo	Pain Relief Rating (PRR)	1 hour	1.9 Units on a scale	Standard Deviation 1
Placebo	Pain Relief Rating (PRR)	3 hours	3.0 Units on a scale	Standard Deviation 1.2
Ibuprofen Sodium	Pain Relief Rating (PRR)	2 hours	2.5 Units on a scale	Standard Deviation 1.2
Ibuprofen Sodium	Pain Relief Rating (PRR)	1 hour	1.9 Units on a scale	Standard Deviation 1.2
Ibuprofen Sodium	Pain Relief Rating (PRR)	3 hours	2.8 Units on a scale	Standard Deviation 1.3
Ibuprofen (Motrin IB)	Pain Relief Rating (PRR)	1 hour	1.6 Units on a scale	Standard Deviation 1
Ibuprofen (Motrin IB)	Pain Relief Rating (PRR)	3 hours	2.7 Units on a scale	Standard Deviation 1.3
Ibuprofen (Motrin IB)	Pain Relief Rating (PRR)	2 hours	2.4 Units on a scale	Standard Deviation 1.2

Comparison: 1 hour: Treatment difference (Ibuprofen sodium - placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.40295% CI: [-0.65, 0.26]ANOVA

Comparison: 1 hour: Treatment difference \[Ibuprofen (Motrin IB) - placebo\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.40795% CI: [-0.64, 0.26]ANOVA

Comparison: 2 hours: Treatment difference (Ibuprofen sodium - placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.31395% CI: [-0.75, 0.24]ANOVA

Comparison: 2 hours: Treatment difference \[Ibuprofen (Motrin IB) - placebo\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.62195% CI: [-0.62, 0.37]ANOVA

Comparison: 3 hours: Treatment difference (Ibuprofen sodium - placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.35295% CI: [-0.79, 0.28]ANOVA

Comparison: 3 hours: Treatment difference \[Ibuprofen (Motrin IB) - placebo\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.57395% CI: [-0.69, 0.38]ANOVA

Secondary

Sum of Pain Relief Rating and Pain Intensity Difference (PRID)

PRID was sum of PID and PRR at each post-dosing time point. The overall possible score range, for PRID was -1 (worst) to 7 (best). PID was derived by subtracting the pain severity score at a given post-dosing time point \[pain severity score range 0 (none) to 3 (severe)\] from the baseline score \[Baseline pain severity score range 2 (moderately severe) to 3 (severe)\]. Total possible score range for PID: -1 (worst) to 3 (best). PRR was assessed on 5-point categorical pain relief rating scale (0=No relief to 4=Complete relief).

Time frame: 1, 2, 3 hours

Population: ITT population included all randomized participants who received study medication and provided a baseline assessment.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Sum of Pain Relief Rating and Pain Intensity Difference (PRID)	2 hours	3.9 Units on a scale	Standard Deviation 1.7
Placebo	Sum of Pain Relief Rating and Pain Intensity Difference (PRID)	1 hour	2.8 Units on a scale	Standard Deviation 1.5
Placebo	Sum of Pain Relief Rating and Pain Intensity Difference (PRID)	3 hours	4.5 Units on a scale	Standard Deviation 2
Ibuprofen Sodium	Sum of Pain Relief Rating and Pain Intensity Difference (PRID)	2 hours	3.7 Units on a scale	Standard Deviation 1.9
Ibuprofen Sodium	Sum of Pain Relief Rating and Pain Intensity Difference (PRID)	1 hour	2.8 Units on a scale	Standard Deviation 1.8
Ibuprofen Sodium	Sum of Pain Relief Rating and Pain Intensity Difference (PRID)	3 hours	4.3 Units on a scale	Standard Deviation 2.1
Ibuprofen (Motrin IB)	Sum of Pain Relief Rating and Pain Intensity Difference (PRID)	1 hour	2.4 Units on a scale	Standard Deviation 1.5
Ibuprofen (Motrin IB)	Sum of Pain Relief Rating and Pain Intensity Difference (PRID)	3 hours	4.1 Units on a scale	Standard Deviation 2.2
Ibuprofen (Motrin IB)	Sum of Pain Relief Rating and Pain Intensity Difference (PRID)	2 hours	3.6 Units on a scale	Standard Deviation 1.9

Comparison: 1 hour: Treatment difference (Ibuprofen sodium - placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.37795% CI: [-0.98, 0.37]ANOVA

Comparison: 1 hour: Treatment difference \[Ibuprofen (Motrin IB) - placebo\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.32495% CI: [-1.01, 0.34]ANOVA

Comparison: 2 hours: Treatment difference (Ibuprofen sodium - placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.27395% CI: [-1.17, 0.33]ANOVA

Comparison: 2 hours: Treatment difference \[Ibuprofen (Motrin IB) - placebo\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.61695% CI: [-0.94, 0.56]ANOVA

Comparison: 3 hours: Treatment difference (Ibuprofen sodium - placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.35695% CI: [-1.24, 0.45]ANOVA

Comparison: 3 hours: Treatment difference \[Ibuprofen (Motrin IB) - placebo\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.72295% CI: [-1, 0.69]ANOVA

Secondary

Time to Confirmed First Perceptible Relief

Participants evaluated the time to first perceptible relief by stopping a stopwatch labeled 'first perceptible relief' at the moment the participant first began to experience any relief. Stopwatch was active up to 3 hours after dosing or until stopped by the participant, or rescue medication was administered. First perceptible relief was considered confirmed by meaningful relief if the participant achieved both first perceptible and meaningful relief by either depressing the second stopwatch or by indicating that his/her first perceptible relief was also meaningful.

Time frame: 0 to 3 hours

Population: ITT population included all randomized participants who received study medication and provided a baseline assessment.

Arm	Measure	Value (MEDIAN)
Placebo	Time to Confirmed First Perceptible Relief	42.3 Minutes
Ibuprofen Sodium	Time to Confirmed First Perceptible Relief	41.7 Minutes
Ibuprofen (Motrin IB)	Time to Confirmed First Perceptible Relief	43.8 Minutes

Comparison: HR and corresponding 95% CI were calculated based on the Wald statistic from the PH model.p-value: 0.07295% CI: [0.41, 1.04]Proportional hazards model

Comparison: HR and corresponding 95% CI were calculated based on the Wald statistic from the PH model.p-value: 0.65295% CI: [0.58, 1.41]Proportional hazards model

Comparison: HR and corresponding 95% CI were calculated based on the Wald statistic from the PH model.p-value: 0.10895% CI: [0.49, 1.07]Proportional hazards model

Secondary

Time to Onset of Meaningful Relief: Remaining Comparisons

Time frame: 0 to 3 hours

Population: ITT population included all randomized participants who received study medication and provided a baseline assessment.

Arm	Measure	Value (MEDIAN)
Placebo	Time to Onset of Meaningful Relief: Remaining Comparisons	48.2 Minutes
Ibuprofen Sodium	Time to Onset of Meaningful Relief: Remaining Comparisons	50.3 Minutes
Ibuprofen (Motrin IB)	Time to Onset of Meaningful Relief: Remaining Comparisons	55.5 Minutes

Comparison: HR and corresponding 95% CI were calculated based on the Wald statistic from the PH model.p-value: 0.30495% CI: [0.5, 1.24]Proportional hazards model

Comparison: HR and corresponding 95% CI were calculated based on the Wald statistic from the PH model.p-value: 0.93695% CI: [0.65, 1.59]Proportional hazards model

Secondary

Time to Treatment Failure

Median time of dropping out of the participants from the study due to lack of efficacy or received rescue medication, whichever came first.

Time frame: 0 to 3 hours

Population: Data was not analyzed as there were no treatment failures observed and no participant received rescue medication in the study.

Secondary

Time-weighted Sum of Pain Intensity Difference (SPID)

SPID: time-weighted sum of PID over 2 and 3 hours. SPID score range was -2(worst) to 6 (best) for SPID 0-2 and -3 (worst) to 9 (best) for SPID 0-3. PID: baseline pain severity score minus pain severity score at a given time point (score range 0=none to 3=severe; baseline score range 2=moderately severe to 3=severe). Total score range for PID: -1(worst) to 3 (best).

Time frame: 0 to 2, 0 to 3 hours

Population: ITT population included all randomized participants who received study medication and provided a baseline assessment.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Time-weighted Sum of Pain Intensity Difference (SPID)	SPID 0-2	2.2 Units on a scale	Standard Deviation 1.3
Placebo	Time-weighted Sum of Pain Intensity Difference (SPID)	SPID 0-3	3.8 Units on a scale	Standard Deviation 2
Ibuprofen Sodium	Time-weighted Sum of Pain Intensity Difference (SPID)	SPID 0-2	2.2 Units on a scale	Standard Deviation 1.3
Ibuprofen Sodium	Time-weighted Sum of Pain Intensity Difference (SPID)	SPID 0-3	3.6 Units on a scale	Standard Deviation 2.1
Ibuprofen (Motrin IB)	Time-weighted Sum of Pain Intensity Difference (SPID)	SPID 0-2	2.0 Units on a scale	Standard Deviation 1.3
Ibuprofen (Motrin IB)	Time-weighted Sum of Pain Intensity Difference (SPID)	SPID 0-3	3.4 Units on a scale	Standard Deviation 2.2

Comparison: SPID 0-2: Treatment difference (Ibuprofen sodium - placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.25995% CI: [-0.75, 0.2]ANOVA

Comparison: SPID 0-2: Treatment difference \[Ibuprofen (Motrin IB) - placebo\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.37895% CI: [-0.69, 0.26]ANOVA

Comparison: SPID 0-2: Treatment difference \[Ibuprofen sodium - Ibuprofen (Motrin IB)\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.76295% CI: [-0.45, 0.33]ANOVA

Comparison: SPID 0-3: Treatment difference (Ibuprofen sodium - placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.28195% CI: [-1.17, 0.34]ANOVA

Comparison: SPID 0-3: Treatment difference \[Ibuprofen (Motrin IB) - placebo\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.58295% CI: [-0.97, 0.55]ANOVA

Comparison: SPID 0-3: Treatment difference \[Ibuprofen sodium - Ibuprofen (Motrin IB)\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.52395% CI: [-0.83, 0.42]ANOVA

Secondary

Time-weighted Sum of Pain Relief Rating and Pain Intensity Difference (SPRID)

SPRID: time-weighted sum of PRID over 2 and 3 hours. SPRID score range was -2(worst) to 14(best) for SPRID 0-2 and -3 (worst) to 21 (best) for SPRID 0-3. PRID: sum of PID and PRR at each time point. Total score range for PRID: -1=worst to 7=best. PID: baseline pain severity score minus pain severity score at a given time point (score range 0=none to 3=severe; baseline score range 2=moderately severe to 3=severe). Total score range for PID: -1(worst) to 3(best), PRR: assessed on 5-point pain relief rating scale (0=No relief to 4=Complete relief).

Time frame: 0 to 2, 0 to 3 hours

Population: ITT population included all randomized participants who received study medication and provided a baseline assessment.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Time-weighted Sum of Pain Relief Rating and Pain Intensity Difference (SPRID)	SPRID 0-2	6.7 Units on a scale	Standard Deviation 3.1
Placebo	Time-weighted Sum of Pain Relief Rating and Pain Intensity Difference (SPRID)	SPRID 0-3	11.2 Units on a scale	Standard Deviation 4.9
Ibuprofen Sodium	Time-weighted Sum of Pain Relief Rating and Pain Intensity Difference (SPRID)	SPRID 0-2	6.5 Units on a scale	Standard Deviation 3.4
Ibuprofen Sodium	Time-weighted Sum of Pain Relief Rating and Pain Intensity Difference (SPRID)	SPRID 0-3	10.8 Units on a scale	Standard Deviation 5.3
Ibuprofen (Motrin IB)	Time-weighted Sum of Pain Relief Rating and Pain Intensity Difference (SPRID)	SPRID 0-2	6.1 Units on a scale	Standard Deviation 3.2
Ibuprofen (Motrin IB)	Time-weighted Sum of Pain Relief Rating and Pain Intensity Difference (SPRID)	SPRID 0-3	10.2 Units on a scale	Standard Deviation 5.2

Comparison: SPRID 0-2: Treatment difference (Ibuprofen sodium - placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.29295% CI: [-2.07, 0.62]ANOVA

Comparison: SPRID 0-2: Treatment difference \[Ibuprofen (Motrin IB) - placebo\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.43995% CI: [-1.87, 0.82]ANOVA

Comparison: SPRID 0-2: Treatment difference \[Ibuprofen sodium - Ibuprofen (Motrin IB)\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.73395% CI: [-1.31, 0.92]ANOVA

Comparison: SPRID 0-3: Treatment difference \[Ibuprofen (Motrin IB) - placebo\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.52695% CI: [-2.8, 1.43]ANOVA

Comparison: SPRID 0-3: Treatment difference \[Ibuprofen sodium - Ibuprofen (Motrin IB)\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.62495% CI: [-2.19, 1.31]ANOVA

Secondary

Time-weighted Sum of Pain Relief Rating (TOTPAR)

TOTPAR: time-weighted sum of PRR over 2 and 3 hours. TOTPAR score range was 0 (worst) to 8 (best) for TOTPAR 0-2 and 0 (worst) to 12 (best) for TOTPAR 0-3. PRR was assessed on a 5-point categorical pain relief rating scale wherein 0=No relief to 4=Complete relief.

Time frame: 0 to 2, 0 to 3 hours

Population: ITT population included all randomized participants who received study medication and provided a baseline assessment.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Time-weighted Sum of Pain Relief Rating (TOTPAR)	TOTPAR 0-2	4.5 Units on a scale	Standard Deviation 2
Placebo	Time-weighted Sum of Pain Relief Rating (TOTPAR)	TOTPAR 0-3	7.5 Units on a scale	Standard Deviation 3.1
Ibuprofen Sodium	Time-weighted Sum of Pain Relief Rating (TOTPAR)	TOTPAR 0-2	4.4 Units on a scale	Standard Deviation 2.3
Ibuprofen Sodium	Time-weighted Sum of Pain Relief Rating (TOTPAR)	TOTPAR 0-3	7.2 Units on a scale	Standard Deviation 3.5
Ibuprofen (Motrin IB)	Time-weighted Sum of Pain Relief Rating (TOTPAR)	TOTPAR 0-2	4.1 Units on a scale	Standard Deviation 2
Ibuprofen (Motrin IB)	Time-weighted Sum of Pain Relief Rating (TOTPAR)	TOTPAR 0-3	6.8 Units on a scale	Standard Deviation 3.2

Comparison: TOTPAR 0-2: Treatment difference (Ibuprofen sodium - placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.32795% CI: [-1.35, 0.45]ANOVA

Comparison: TOTPAR 0-2: Treatment difference \[Ibuprofen (Motrin IB) - placebo\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.48995% CI: [-1.21, 0.58]ANOVA

Comparison: TOTPAR 0-2: Treatment difference \[Ibuprofen sodium - Ibuprofen (Motrin IB)\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.72695% CI: [-0.88, 0.61]ANOVA

Comparison: TOTPAR 0-3: Treatment difference (Ibuprofen sodium - placebo) and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.3295% CI: [-2.09, 0.69]ANOVA

Comparison: TOTPAR 0-3: Treatment difference \[Ibuprofen (Motrin IB) - placebo\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.50695% CI: [-1.86, 0.92]ANOVA

Comparison: TOTPAR 0-3: Treatment difference \[Ibuprofen sodium - Ibuprofen (Motrin IB)\] and corresponding 95% CI were calculated based on LS means from the ANOVA model.p-value: 0.69195% CI: [-1.38, 0.92]ANOVA

Source: ClinicalTrials.gov · Data processed: Mar 6, 2026

Study Evaluating A Novel Ibuprofen Formulation In Episodic Tension-Type Headache

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Participant flow

Participants by arm

Baseline characteristics

Adverse events

Outcome results

Time to Onset of Meaningful Relief for Ibuprofen Sodium Versus Ibuprofen (Motrin IB) Tablet

Time-weighted Sum of Pain Relief Rating and Pain Intensity Difference From 0-3 Hours (SPRID 0-3) for Ibuprofen Sodium Versus Placebo Tablet

Cumulative Percentage of Participants With Complete Relief

Cumulative Percentage of Participants With Confirmed First Perceptible Relief

Cumulative Percentage of Participants With Meaningful Relief

Cumulative Percentage of Participants With Treatment Failure

Pain Intensity Difference (PID)

Pain Relief Rating (PRR)

Sum of Pain Relief Rating and Pain Intensity Difference (PRID)

Time to Confirmed First Perceptible Relief

Time to Onset of Meaningful Relief: Remaining Comparisons

Time to Treatment Failure

Time-weighted Sum of Pain Intensity Difference (SPID)

Time-weighted Sum of Pain Relief Rating and Pain Intensity Difference (SPRID)

Time-weighted Sum of Pain Relief Rating (TOTPAR)