A Study to Assess Efficacy and Tolerability of Ketoprofen 40 mg Granules vs Placebo

The primary efficacy endpoint is the pain intensity assessment during 6 hours after molar tooth extraction measured as an area under the curve (AUC) of pain intensity assessed with a visual analogue scale (VAS). More precisely, pain is assessed by a horizontal 100 mm scale where 0 mm = no pain and 100 mm = worst pain imaginable, at the timepoints specified here under in the interval from time 0 (baseline value of VAS) to 6 hours after the drug administration. The AUC0-6h is calculated using the trapezoidal rule. Please note that at 0' (just before taking the first medication) VAS should be \>30 mm. The higher the score, the worse the result.

Time frame: time 0', 5', 10', 15', 30', 60' (1 hour), 90' (1.5 hours), 120' (2 hours), 180' (3 hours), 240' (4 hours), 300' (5 hours), and 360' (6 hours) post-treatment

Population: The Intent-to-treat (ITT) population included all randomized patients who received at least one dose of study medication and have at least one post-baseline18 efficacy measurement; one patient in the ketoprofen group had missing data of the pain intensity VAS and such data were not replaced according to rules for LOCF; hence no AUC for this patient was calculated.

The primary efficacy endpoint is the pain intensity assessment during 6 hours after molar tooth extraction measured as an area under the curve (AUC) of pain intensity assessed with a visual analogue scale (VAS). More precisely, pain is assessed by a horizontal 100 mm scale where 0 = no pain and 100 = worst pain imaginable, at the timepoints specified here under in the interval from time 0 (baseline value of VAS) to 6 hours after the drug administration. The AUC0-6h is calculated using the trapezoidal rule. Please note that at 0' (just before taking the first medication) VAS should be \>30 mm. The higher the score, the worse the result.

Time frame: time 0', 5', 10', 15', 30', 60' (1 hour), 90' (1.5 hours), 120' (2 hours), 180' (3 hours), 240' (4 hours), 300' (5 hours), and 360' (6 hours) post-treatment

Population: The Per protocol population included those patients who had completed the study treatment period, had all assessments for the primary efficacy analysis and considered compliant. The patients were compliant if they did not have any major protocol violations in the course of the study. For the PP population no data could be missing, hence there were no LOCF or other methods applied.

In addition, area under the curve for pain relief assessment since 5 minutes till 6 hours after the drug administration was evaluated.

Time frame: from 5 min to 6 hours post-dose

Population: ITT population included all randomized patients who received at least one dose of study medication and have at least one post-baseline 18 efficacy measurement; one patient in the ketoprofen group had missing data of the pain intensity VAS and such data were not replaced according to rules for LOCF; hence no AUC for this patient was calculated.~PP population included those patients who had completed the study treatment period, had all assessments for the primary efficacy analysis and compliant.

The patients were asked to provide their current overall assessment answering the question Considering all the ways that the pain affects you, how well are you doing? The patients marked the answer on the 5-point scale: 1 = very good, 2 = good, 3= satisfactory, 4 = poor, 5 = very poor. If a patient takes rescue medication, the Patient's overall assessment will be performed after the last VAS assessment.

Time frame: Day 1 at 360' or > 60' in case of early discontinuation.

Population: The Intent-to-treat (ITT) population included all randomized patients who received at least one dose of study medication and have at least one post-baseline18 efficacy measurement; one patient in the ketoprofen group had missing data of the pain intensity VAS and such data were not replaced according to rules for LOCF; hence no AUC for this patient was calculated.

This outcome analyzed the evolution and the profile of pain by a horizontal 100 mm Visual Analogue Scale (VAS): 0 no pain - 100 worst pain imaginable at 0' (just before taking the first medication VAS should be \>30 mm) and 5', 10', 15', 30', 60' (1 hour), 90' (1.5 hours), 120' (2 hours), 180' (3 hours), 240'(4 hours), 300' (5 hours), and 360' (6 hours) after the drug administration. The higher the score, the worse the result.

Time frame: From time 0 (baseline value of VAS) to 6 hours post-treatment at: 0', 5', 10', 15', 30', 45', 60' (1 hour), 90' (1.5 hours), 120' (2 hours), 180' (3 hours), 240' (4 hours), 300' (5 hours), and 360' (6 hours) after the drug administration.

Population: The Intent-to-treat (ITT) population included all randomized patients who received at least one dose of study medication and have at least one post-baseline18 efficacy measurement; one patient in the ketoprofen group had missing data of the pain intensity VAS and such data were not replaced according to rules for LOCF; hence no AUC for this patient was calculated.

This outcome analyzed the evolution of pain relief after administration of OKITASK® and after administration of Placebo, assessed by a horizontal 100 mm Visual Analogue Scale (VAS): 0 no pain relief - 100 maximum relief imaginable at: 0' (just before taking the first medication VAS should be \>30 mm) and 5', 10', 15', 30', 60' (1 hour), 90' (1.5 hours), 120' (2 hours), 180' (3 hours), 240'(4 hours), 300' (5 hours), and 360' (6 hours) after the drug administration. The higher the score, the best the result.

Time frame: From time 0 (baseline value of VAS) to 6 hours post-treatment at: 5', 10', 15', 30', 45', 60' (1 hour), 90' (1.5 hours), 120' (2 hours), 180' (3 hours), 240' (4 hours), 300' (5 hours), and 360' (6 hours) after the drug administration.

Population: The Intent-to-treat (ITT) population included all randomized patients who received at least one dose of study medication and have at least one post-baseline18 efficacy measurement; one patient in the ketoprofen group had missing data of the pain intensity VAS and such data were not replaced according to rules for LOCF; hence no AUC for this patient was calculated.

TFPR was measured by stopwatches, a timepiece designed to measure the amount of time that elapses between its activation and deactivation. Upon study drug administration the patients immediately started a stopwatch, once the patient felt first perceptible pain relief, the stopwatch was stopped. The time between activation and deactivation of a stopwatch defined the outcome measure data. The shortest the time, the better the outcome. Kaplan-Meier estimation of TFPR was expressed by median and 95% CI.

Time frame: Day 1

Population: The Intent-to-treat (ITT) population included all randomized patients who received at least one dose of study medication and have at least one post-baseline18 efficacy measurement; one patient in the ketoprofen group had missing data of the pain intensity VAS and such data were not replaced according to rules for LOCF; hence no AUC for this patient was calculated.

TMPR will be measured by stopwatches, a timepiece designed to measure the amount of time that elapses between its activation and deactivation. Upon study drug administration the patients will immediately start a stopwatch, once the patient feels meaningful perceptible pain relief, the stopwatch is stopped. The time between activation and deactivation of a stopwatch defines the outcome measure data.

Time frame: Day 1

Population: The Intent-to-treat (ITT) population included all randomized patients who received at least one dose of study medication and have at least one post-baseline18 efficacy measurement; one patient in the ketoprofen group had missing data of the pain intensity VAS and such data were not replaced according to rules for LOCF; hence no AUC for this patient was calculated.