Trial Outcomes & Findings for Ibuprofen/Caffeine Lower Back or Neck Pain Study (NCT NCT03003000)

Last Updated: 2019-06-07

Results Overview

The change in pain on movement (POM) with regard to the worst procedure (WP), i.e. the procedure with the highest pain score at baseline (POMwp), between baseline (morning of Day 1, pre-dosing) and Day 2 (morning, 2 hour (h) after drug intake). POM was assessed by the patient at the performance of one standardized, muscle group specific movement and was measured by a numerical rating scale ranging from 0 = 'no pain'to 10 = 'worst pain possible for this condition'. The procedure resulting in highest POM at baseline (worst procedure, POMWP) was repeated for an individual patient. If 2 or more procedures gave the same highest POM, the patient was asked which of the procedures giving the highest POM scores he/she considered the most unpleasant. Change in POMwp was calculated as baseline POMwp - POMwp at Day 2 - indicating a reduction in POMwp, where the result is positive.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

635 participants

Primary outcome timeframe

Baseline and Day 2

Results posted on

2019-06-07

Participant Flow

This was a randomized, placebo and active-controlled, double-blind, 3-arm, parallel trial, comparing the effect of the fixed dose combination of 400 milligram (mg) ibuprofen\&100 mg caffeine versus 400 mg ibuprofen and placebo in patients with acute neck or back pain randomly assigned in 2:2:1 ratio respectively.

All patients were screened for eligibility to participate in the trial. Patients attended specialist sites to ensure that all patients met all inclusion/exclusion criteria. Patients were not to be entered/randomised to trial treatment if any one of the specific entry criteria were not met.

Participant milestones

Participant milestones
Measure	Placebo Patients were administered placebo matching ibuprofen and ibuprofen/caffeine film-coated tablets orally 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Ibuprofen Patients were administered film-coated tablets orally containing 400 mg ibuprofen 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Ibuprofen and Caffeine Patients were administered film-coated tablets orally containing 400 mg ibuprofen and 100 mg caffeine 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.
Overall Study STARTED	126	253	256
Overall Study COMPLETED	121	249	251
Overall Study NOT COMPLETED	5	4	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Patients were administered placebo matching ibuprofen and ibuprofen/caffeine film-coated tablets orally 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Ibuprofen Patients were administered film-coated tablets orally containing 400 mg ibuprofen 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Ibuprofen and Caffeine Patients were administered film-coated tablets orally containing 400 mg ibuprofen and 100 mg caffeine 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.
Overall Study Adverse Event	1	2	3
Overall Study Lack of Efficacy	1	0	0
Overall Study Non-compliant with protocol	0	1	1
Overall Study Refused to continue medication	2	0	0
Overall Study Other than listed	1	1	1

Baseline Characteristics

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=126 Participants Patients were administered placebo matching ibuprofen and ibuprofen/caffeine film-coated tablets orally 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Ibuprofen n=253 Participants Patients were administered film-coated tablets orally containing 400 mg ibuprofen 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Ibuprofen and Caffeine n=256 Participants Patients were administered film-coated tablets orally containing 400 mg ibuprofen and 100 mg caffeine 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Total n=635 Participants Total of all reporting groups
Age, Continuous	46.3 Years STANDARD_DEVIATION 15.00 • n=5 Participants • TS	45.5 Years STANDARD_DEVIATION 16.40 • n=7 Participants • TS	44.8 Years STANDARD_DEVIATION 17.00 • n=5 Participants • TS	45.4 Years STANDARD_DEVIATION 16.36 • n=4 Participants • TS
Sex: Female, Male Female	75 Participants n=5 Participants • TS	155 Participants n=7 Participants • TS	143 Participants n=5 Participants • TS	373 Participants n=4 Participants • TS
Sex: Female, Male Male	51 Participants n=5 Participants • TS	98 Participants n=7 Participants • TS	113 Participants n=5 Participants • TS	262 Participants n=4 Participants • TS
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants • TS	0 Participants n=7 Participants • TS	0 Participants n=5 Participants • TS	1 Participants n=4 Participants • TS
Ethnicity (NIH/OMB) Not Hispanic or Latino	125 Participants n=5 Participants • TS	253 Participants n=7 Participants • TS	256 Participants n=5 Participants • TS	634 Participants n=4 Participants • TS
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • TS	0 Participants n=7 Participants • TS	0 Participants n=5 Participants • TS	0 Participants n=4 Participants • TS
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants • TS	0 Participants n=7 Participants • TS	0 Participants n=5 Participants • TS	1 Participants n=4 Participants • TS
Race (NIH/OMB) Asian	0 Participants n=5 Participants • TS	1 Participants n=7 Participants • TS	3 Participants n=5 Participants • TS	4 Participants n=4 Participants • TS
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants • TS	0 Participants n=7 Participants • TS	0 Participants n=5 Participants • TS	0 Participants n=4 Participants • TS
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants • TS	3 Participants n=7 Participants • TS	2 Participants n=5 Participants • TS	5 Participants n=4 Participants • TS
Race (NIH/OMB) White	125 Participants n=5 Participants • TS	249 Participants n=7 Participants • TS	251 Participants n=5 Participants • TS	625 Participants n=4 Participants • TS
Race (NIH/OMB) More than one race	0 Participants n=5 Participants • TS	0 Participants n=7 Participants • TS	0 Participants n=5 Participants • TS	0 Participants n=4 Participants • TS
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • TS	0 Participants n=7 Participants • TS	0 Participants n=5 Participants • TS	0 Participants n=4 Participants • TS
Pain on movement worst procedure score (0-10)	6.9 Unit on scale STANDARD_DEVIATION 1.07 • n=5 Participants • Treated Set	6.8 Unit on scale STANDARD_DEVIATION 1.15 • n=7 Participants • Treated Set	6.6 Unit on scale STANDARD_DEVIATION 1.15 • n=5 Participants • Treated Set	6.7 Unit on scale STANDARD_DEVIATION 1.14 • n=4 Participants • Treated Set

PRIMARY outcome

Timeframe: Baseline and Day 2

Population: Full analysis set (FAS): FAS comprised all patients in the TS who provided a baseline value for POMWP at Visit 1 (before drug intake) and at least 1 POMWP post-treatment value at Visit 1 (Day 1 morning, 2 h after drug intake) and at Visit 2 (Day 2, morning, 2 h after drug intake).

Outcome measures

Outcome measures
Measure	Placebo n=126 Participants Patients were administered placebo matching ibuprofen and ibuprofen/caffeine film-coated tablets orally 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Ibuprofen n=253 Participants Patients were administered film-coated tablets orally containing 400 mg ibuprofen 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Ibuprofen and Caffeine n=256 Participants Patients were administered film-coated tablets orally containing 400 mg ibuprofen and 100 mg caffeine 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.
Change in Pain on Movement (POM) With Regard to the Worst Procedure (WP) Between Baseline and Day 2 (Morning, 2 Hours After Drug Intake)	1.712 Unit on scale Standard Error 0.1422	1.998 Unit on scale Standard Error 0.1042	1.869 Unit on scale Standard Error 0.1030

SECONDARY outcome

Timeframe: Baseline, Day 1, Day 2 and Day 4 (morning)

Population: Treated Set (TS): The TS comprised all randomised patients who took at least 1 dose of trial medication.

This is a key secondary endpoint. The area under the curve (AUC) for pain on movement (POM) with regard to the worst procedure (POMwp) between baseline and Day 4 (morning), (POMwpAUC72h ). POM was assessed by the patient at the performance of one standardized, muscle group specific movement and was measured by a numerical rating scale ranging from 0 = 'no pain'to 10 = 'worst pain possible for this condition'. A higher AUC value indicates higher POMwp

Outcome measures

Outcome measures
Measure	Placebo n=126 Participants Patients were administered placebo matching ibuprofen and ibuprofen/caffeine film-coated tablets orally 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Ibuprofen n=253 Participants Patients were administered film-coated tablets orally containing 400 mg ibuprofen 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Ibuprofen and Caffeine n=256 Participants Patients were administered film-coated tablets orally containing 400 mg ibuprofen and 100 mg caffeine 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.
The Area Under the Curve (AUC) for Pain on Movement (POM) With Regard to the Worst Procedure (POMwp) Between Baseline and Day 4 (Morning) (POMwpAUC72hour (h))	4.800 Unit on scale Standard Error 0.1266	4.461 Unit on scale Standard Error 0.0942	4.512 Unit on scale Standard Error 0.0931

SECONDARY outcome

Timeframe: Baseline, Day 1, Day 2, Day 4 and Day 6 (morning)

Population: TS

This is a key secondary endpoint. The area under the curve for pain on movement with regard to the worst procedure between baseline and Day 6 (morning) (POM(WP)AUC(120h). POM was assessed by the patient at the performance of one standardized, muscle group specific movement and was measured by a numerical rating scale ranging from 0 = 'no pain'to 10 = 'worst pain possible for this condition'. A higher AUC value indicates higher POMwp.

Outcome measures

Outcome measures
Measure	Placebo n=126 Participants Patients were administered placebo matching ibuprofen and ibuprofen/caffeine film-coated tablets orally 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Ibuprofen n=253 Participants Patients were administered film-coated tablets orally containing 400 mg ibuprofen 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Ibuprofen and Caffeine n=256 Participants Patients were administered film-coated tablets orally containing 400 mg ibuprofen and 100 mg caffeine 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.
The Area Under the Curve (AUC) for the Procedure With the Highest Pain Score at Baseline (POMWP) Between Baseline and Day 6 (Morning) (POM(WP)AUC(120h))	4.175 Unit on scale Standard Error 0.1334	3.718 Unit on scale Standard Error 0.0992	3.776 Unit on scale Standard Error 0.0981

SECONDARY outcome

Timeframe: Baseline and Day 2 (morning, 2 h after drug intake)

Population: TS

Change in pressure algometry between baseline and Day 2 (morning, 2 h after drug intake). Pressure algometry was determined by the investigator as the pressure value (N/cm2) at a defined trigger point which is located in the area of POMWP. The measurement was performed by using a Somedic Algometer (Somedic AB, Sweden) or an equivalent calibrated and certified device. The pain reaction was determined by placing the algometer on the trigger point, i.e. an area of 1 cm² for which the patient indicated most painful tenderness. The pressure was constantly increased until the patient asked not to increase the pressure anymore. Upon this pain reaction, the corresponding pressure value was documented in the Electronic case report form (eCRF). The trigger point was to be marked with a ball pen to be able to repeat the subsequent assessment at the same position. Change in pressure was calculated as baseline pressure - pressure at Day 2, with a negative result indicating an improvement.

Outcome measures

Outcome measures
Measure	Placebo n=126 Participants Patients were administered placebo matching ibuprofen and ibuprofen/caffeine film-coated tablets orally 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Ibuprofen n=253 Participants Patients were administered film-coated tablets orally containing 400 mg ibuprofen 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Ibuprofen and Caffeine n=256 Participants Patients were administered film-coated tablets orally containing 400 mg ibuprofen and 100 mg caffeine 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.
Change in Pressure Algometry Between Baseline and Day 2 (Morning, 2 Hour After Drug Intake)	-3.734 newton/centimeter² (N/cm^2) Standard Error 0.6107	-3.331 newton/centimeter² (N/cm^2) Standard Error 0.4396	-3.175 newton/centimeter² (N/cm^2) Standard Error 0.4366

SECONDARY outcome

Timeframe: At the end of treatment (morning of Day 6)

Population: TS including participants with available data for global assessment of efficacy

Global assessment of efficacy by the patient at the end of treatment (morning of Day 6) is presented. The patient/investigator assessed the overall efficacy of the trial treatment on a 4-point verbal rating scale by answering the question: "How would you rate the overall effect of the trial medication for relieving back or neck pain?" (0 = poor; 1 = fair; 2 = good; 3 = very good).

Outcome measures

Outcome measures
Measure	Placebo n=123 Participants Patients were administered placebo matching ibuprofen and ibuprofen/caffeine film-coated tablets orally 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Ibuprofen n=253 Participants Patients were administered film-coated tablets orally containing 400 mg ibuprofen 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Ibuprofen and Caffeine n=255 Participants Patients were administered film-coated tablets orally containing 400 mg ibuprofen and 100 mg caffeine 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.
Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6) Very good	14 Participants	43 Participants	41 Participants
Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6) Good	46 Participants	115 Participants	116 Participants
Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6) Fair	35 Participants	57 Participants	66 Participants
Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6) Poor	28 Participants	38 Participants	32 Participants

SECONDARY outcome

Timeframe: Baseline and Day 2 (morning, 2 h after drug intake)

Population: TS

Number of patients with a decrease in POMwp of at least 30% or 50% between baseline and Day 2 (morning, 2 h after drug intake.

Outcome measures

Outcome measures
Measure	Placebo n=126 Participants Patients were administered placebo matching ibuprofen and ibuprofen/caffeine film-coated tablets orally 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Ibuprofen n=253 Participants Patients were administered film-coated tablets orally containing 400 mg ibuprofen 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Ibuprofen and Caffeine n=256 Participants Patients were administered film-coated tablets orally containing 400 mg ibuprofen and 100 mg caffeine 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.
Number of Patients With a Decrease in POMwp of at Least 30% or 50% Between Baseline and Day 2 (Morning, 2 h After Drug Intake) Patients with a decrease of ≥30%	49 Participants	111 Participants	101 Participants
Number of Patients With a Decrease in POMwp of at Least 30% or 50% Between Baseline and Day 2 (Morning, 2 h After Drug Intake) Patients with a decrease of ≥50%	17 Participants	59 Participants	44 Participants

SECONDARY outcome

Timeframe: Within 2 h after the first dose of trial medication

Population: TS

Time to event analysis of patients with first meaningful POMwp relief within 2 h after the first dose of trial medication. The percentage of observed patients with a meaningful POMwp relief within 2 h after the first dose of trial medication was reported. The procedure which resulted in the highest POM at baseline (POMwp) was repeated by the investigator 10, 20, 30, 60 and 120 min after the first dose of trial medication. The POMwp relief score (POMwpRS) was assessed by the patient at each of these time points by using a 5-point verbal rating scale (0 = no POMwp relief; 1 = little or perceptible POMwp relief; 2 = meaningful POMwp relief; 3 = a lot of POMwp relief; 4 = complete POMwp relief). The time to first meaningful POMWP relief was the earliest assessment time point after the first application of the trial medication at which the patient reported a score of ≥2.

Outcome measures

Outcome measures
Measure	Placebo n=126 Participants Patients were administered placebo matching ibuprofen and ibuprofen/caffeine film-coated tablets orally 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Ibuprofen n=253 Participants Patients were administered film-coated tablets orally containing 400 mg ibuprofen 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.	Ibuprofen and Caffeine n=256 Participants Patients were administered film-coated tablets orally containing 400 mg ibuprofen and 100 mg caffeine 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.
Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication 0 to ≤10 min	1.6 Percentage of participants	0.8 Percentage of participants	0.8 Percentage of participants
Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication >10 to ≤20 min	1.6 Percentage of participants	2.0 Percentage of participants	1.2 Percentage of participants
Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication >20 to ≤30 min	1.6 Percentage of participants	2.4 Percentage of participants	2.0 Percentage of participants
Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication >30 to ≤60 min	5.6 Percentage of participants	9.1 Percentage of participants	5.5 Percentage of participants
Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication >60 to <=120	8.7 Percentage of participants	8.3 Percentage of participants	10.2 Percentage of participants
Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication >120 min	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Ibuprofen

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Ibuprofen and Caffeine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Boehringer Ingelheim, Call Centre

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
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