Back Pain, Neck Pain
Conditions
Brief summary
To assess the efficacy and safety of a 400 mg ibuprofen/100 mg caffeine tablet in comparison to a 400 mg ibuprofen tablet for the treatment of acute lower back or neck pain. To assess the safety and tolerability of a 400 mg ibuprofen/100 mg caffeine tablet in comparison to a 400 mg ibuprofen tablet and a placebo tablet.
Interventions
DRUGibuprofen
DRUGcaffeine
DRUGplacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed and dated written informed consent at Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation. * Male or female patients who are \>=18 years with current diagnosis of acute back pain or of neck pain for at least 24 hours, but less than 21 days. * Acute back pain or acute neck pain resulting in Pain on Movement (POM) \>=5 on the 0-10 Numerical Rating Scale (NRS) for at least one POM procedure out of 5 standardised procedures. * Sensitivity to algometric pressure on the painful trigger point \<= 25 N/cm². * Women of childbearing potential must be ready and able to use highly effective methods of birth control. * Reliable, cooperative, and of adequate intelligence to record the requested information on the analgesic questionnaires. * Examined by the attending physician and medically cleared to participate in the study * In good general health, with a body mass index (BMI) \< 30, and have no contraindications to any of the study medication
Exclusion criteria
* History of 3 or more episodes of back or neck pain in the last 6 months excluding the current episode. * Patients with pain at rest \>= 9 * Patient with chronic back or neck pain as defined as pain for 3 weeks or longer. * Back or neck pain that is attributable to any identifiable cause (eg. disc prolapse, spondylolisthesis, osteomalacia, inflammatory arthritis, metabolic, neurological diseases or tumour) * Any strains of the back or neck muscles documented by clinical evaluation and anamnesis that occurred 21 days to 3 months prior to the screening visit. * Surgery due to back or neck pain or rehabilitation due to back or neck pain in the last 12 months. * Prior use within the last 3 days before Visit 1 or concomitant use of any anti- inflammatory drugs, heparinoids, muscle relaxants or analgesics (including but not limited to short-acting glucocorticoids, non-steroidal anti-inflammatory drugs \[NSAIDs\], herbal preparations) for the same indication or other indications. * Spinal injections should have been discontinued in due time (investigator's judgment) before patient enrollment to allow complete wash-out of the active ingredient based on investigator's judgment. * Known severe hepatocellular insufficiency, severe renal insufficiency or Gilbert's syndrome (Morbus Meulengracht) * Patients taking Central Nervous System (CNS) or other psychotropic drugs, or any nutritional supplement known to have psychotropic effects such as St. John's Wort, Chapparal, Comfrey, Germander, Gin Bu Huan, Kava, Pennyroyal Skullcap, or Valerian within two months of taking the first dose of study medication. Patients who have been on stable doses of these medications for at least two months will be allowed into the study, as long as they maintain this dose throughout the study, and their condition is judged stable by the Principal Investigator * Any other medical condition that would interfere with efficacy and safety assessments based on investigator's judgment or any on-going clinical condition that would jeopardize patient's or site personnel's safety or study compliance based on investigator judgment * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pain on Movement (POM) With Regard to the Worst Procedure (WP) Between Baseline and Day 2 (Morning, 2 Hours After Drug Intake) | Baseline and Day 2 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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)) | Baseline, Day 1, Day 2, Day 4 and Day 6 (morning) | 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. |
| Change in Pressure Algometry Between Baseline and Day 2 (Morning, 2 Hour After Drug Intake) | Baseline and Day 2 (morning, 2 h after drug intake) | 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. |
| 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)) | Baseline, Day 1, Day 2 and Day 4 (morning) | 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 |
| 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) | Baseline and Day 2 (morning, 2 h after drug intake) | 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. |
| Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication | Within 2 h after the first dose of trial medication | 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. |
| Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6) | At the end of treatment (morning of Day 6) | 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). |
Countries
Germany, Russia
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 126 |
| 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. | 253 |
| 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. | 256 |
| Total | 635 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| 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 | Other than listed | 1 | 1 | 1 |
| Overall Study | Refused to continue medication | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Ibuprofen | Ibuprofen and Caffeine | Total |
|---|---|---|---|---|
| Age, Continuous | 46.3 Years STANDARD_DEVIATION 15 | 45.5 Years STANDARD_DEVIATION 16.4 | 44.8 Years STANDARD_DEVIATION 17 | 45.4 Years STANDARD_DEVIATION 16.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 125 Participants | 253 Participants | 256 Participants | 634 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Pain on movement worst procedure score (0-10) | 6.9 Unit on scale STANDARD_DEVIATION 1.07 | 6.8 Unit on scale STANDARD_DEVIATION 1.15 | 6.6 Unit on scale STANDARD_DEVIATION 1.15 | 6.7 Unit on scale STANDARD_DEVIATION 1.14 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 125 Participants | 249 Participants | 251 Participants | 625 Participants |
| Sex: Female, Male Female | 75 Participants | 155 Participants | 143 Participants | 373 Participants |
| Sex: Female, Male Male | 51 Participants | 98 Participants | 113 Participants | 262 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 126 | 0 / 253 | 0 / 256 |
| other Total, other adverse events | 0 / 126 | 0 / 253 | 0 / 256 |
| serious Total, serious adverse events | 0 / 126 | 0 / 253 | 0 / 256 |
Outcome results
Primary
Change in Pain on Movement (POM) With Regard to the Worst Procedure (WP) Between Baseline and Day 2 (Morning, 2 Hours After Drug Intake)
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.
Time frame: 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).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Ibuprofen | Change in Pain on Movement (POM) With Regard to the Worst Procedure (WP) Between Baseline and Day 2 (Morning, 2 Hours After Drug Intake) | 1.998 Unit on scale | Standard Error 0.1042 |
| Ibuprofen and Caffeine | Change in Pain on Movement (POM) With Regard to the Worst Procedure (WP) Between Baseline and Day 2 (Morning, 2 Hours After Drug Intake) | 1.869 Unit on scale | Standard Error 0.103 |
Comparison: Superiority of ibuprofen and caffeine versus ibuprofen as well as ibuprofen and caffeine versus placebo had to be shown to reject the overall null hypothesis that there is no difference in change in POMWP between baseline and Day 2 (morning, 2 h after drug intake) between patients treated with ibuprofen/caffeine and patients treated with placebo.p-value: 0.344695% CI: [-0.168, 0.48]Mixed effect Model Repeated Measurement
Comparison: Superiority of ibuprofen and caffeine versus ibuprofen as well as ibuprofen and caffeine versus placebo had to be shown to reject the overall null hypothesis that there is no difference in change in POMWP between baseline and Day 2 (morning, 2 h after drug intake) between patients treated with ibuprofen/caffeine and patients treated with ibuprofen.p-value: 0.335895% CI: [-0.392, 0.134]Mixed effect Model Repeat Measurement
Secondary
Change in Pressure Algometry Between Baseline and Day 2 (Morning, 2 Hour After Drug Intake)
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.
Time frame: Baseline and Day 2 (morning, 2 h after drug intake)
Population: TS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Ibuprofen | Change in Pressure Algometry Between Baseline and Day 2 (Morning, 2 Hour After Drug Intake) | -3.331 newton/centimeter² (N/cm^2) | Standard Error 0.4396 |
| Ibuprofen and Caffeine | Change in Pressure Algometry Between Baseline and Day 2 (Morning, 2 Hour After Drug Intake) | -3.175 newton/centimeter² (N/cm^2) | Standard Error 0.4366 |
Comparison: Mixed effect model for repeated measures (MMRM) includes fixed, categorical effects of treatment, country, worst procedure site, time and interaction terms for treatment-by-time as well as the continuous fixed covariates of baseline pressure algometry and baseline-by-time interaction, using unstructured covariance matrix.p-value: 0.439895% CI: [-0.861, 1.979]Mixed effect model for repeated measures
Comparison: MMRM includes fixed, categorical effects of treatment, country, worst procedure site, time and interaction terms for treatment-by-time as well as the continuous fixed covariates of baseline pressure algometry and baseline-by-time interaction, using unstructured covariance matrix.p-value: 0.791195% CI: [-1.002, 1.314]Mixed effect Model Repeat Measurement
Secondary
Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6)
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).
Time frame: At the end of treatment (morning of Day 6)
Population: TS including participants with available data for global assessment of efficacy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6) | Very good | 14 Participants |
| Placebo | Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6) | Good | 46 Participants |
| Placebo | Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6) | Fair | 35 Participants |
| Placebo | Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6) | Poor | 28 Participants |
| Ibuprofen | Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6) | Poor | 38 Participants |
| Ibuprofen | Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6) | Very good | 43 Participants |
| Ibuprofen | Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6) | Fair | 57 Participants |
| Ibuprofen | Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6) | Good | 115 Participants |
| Ibuprofen and Caffeine | Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6) | Poor | 32 Participants |
| Ibuprofen and Caffeine | Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6) | Good | 116 Participants |
| Ibuprofen and Caffeine | Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6) | Fair | 66 Participants |
| Ibuprofen and Caffeine | Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6) | Very good | 41 Participants |
p-value: 0.004595% CI: [1.195, 2.642]Regression, Logistic
p-value: 0.960395% CI: [0.732, 1.389]Regression, Logistic
Secondary
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)
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.
Time frame: Baseline and Day 2 (morning, 2 h after drug intake)
Population: TS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Ibuprofen | 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% | 111 Participants |
| Ibuprofen | 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% | 59 Participants |
| Ibuprofen and Caffeine | 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% | 101 Participants |
| Ibuprofen and Caffeine | 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% | 44 Participants |
p-value: 0.312995% CI: [0.586, 1.187]likelihood-ratio test
p-value: 0.330195% CI: [0.736, 2.494]likelihood-ratio test
p-value: 0.086495% CI: [0.437, 1.057]likelihood-ratio test
p-value: 0.902295% CI: [0.663, 1.592]likelihood-ratio test
Secondary
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))
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
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Ibuprofen | 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)) | 4.461 Unit on scale | Standard Error 0.0942 |
| Ibuprofen and Caffeine | 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)) | 4.512 Unit on scale | Standard Error 0.0931 |
p-value: 0.047495% CI: [-0.572, -0.003]ANCOVA
p-value: 0.665895% CI: [-0.18, 0.282]ANCOVA
Secondary
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))
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.
Time frame: Baseline, Day 1, Day 2, Day 4 and Day 6 (morning)
Population: TS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Ibuprofen | 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)) | 3.718 Unit on scale | Standard Error 0.0992 |
| Ibuprofen and Caffeine | 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)) | 3.776 Unit on scale | Standard Error 0.0981 |
p-value: 0.009195% CI: [-0.698, -0.1]ANCOVA
p-value: 0.638795% CI: [-0.185, 0.302]ANCOVA
Secondary
Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication
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.
Time frame: Within 2 h after the first dose of trial medication
Population: TS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication | >60 to <=120 | 8.7 Percentage of participants |
| Placebo | Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication | >120 min | 0 Percentage of participants |
| Ibuprofen | Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication | >120 min | 0 Percentage of participants |
| Ibuprofen | Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication | 0 to ≤10 min | 0.8 Percentage of participants |
| Ibuprofen | Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication | >30 to ≤60 min | 9.1 Percentage of participants |
| Ibuprofen | Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication | >60 to <=120 | 8.3 Percentage of participants |
| Ibuprofen | Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication | >10 to ≤20 min | 2.0 Percentage of participants |
| Ibuprofen | Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication | >20 to ≤30 min | 2.4 Percentage of participants |
| Ibuprofen and Caffeine | Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication | >10 to ≤20 min | 1.2 Percentage of participants |
| Ibuprofen and Caffeine | Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication | >20 to ≤30 min | 2.0 Percentage of participants |
| Ibuprofen and Caffeine | Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication | >120 min | 0 Percentage of participants |
| Ibuprofen and Caffeine | Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication | >30 to ≤60 min | 5.5 Percentage of participants |
| Ibuprofen and Caffeine | Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication | 0 to ≤10 min | 0.8 Percentage of participants |
| Ibuprofen and Caffeine | Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication | >60 to <=120 | 10.2 Percentage of participants |
p-value: 0.9384Log Rank
p-value: 0.3534Log Rank