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

Dompé Farmaceutici S.p.A70 enrolled

Overview

Primary objective: To assess the efficacy of OKITASK® 40 mg granules versus Placebo in patients with acute pain syndrome after removal of one molar tooth by comparing AUC0-6h of posttreatment pain profile measured by VAS. Secondary objectives: To assess the following efficacy and safety parameters of OKITASK® 40 mg granules versus Placebo in patients with acute pain syndrome after removal of one molar tooth: * Time profile of pain and time profile of pain relief using VAS scales * Time to first perceptible pain relief (TFPR) and time to meaningful pain relief (TMPR) * Proportion of patients requiring rescue medication (analgesia) and time to rescue analgesia * Patient's overall assessment * Rate of adverse events (AE)

This is a multicenter, double blind, randomized, parallel groups study to assess the efficacy and tolerability after single oral administration of Ketoprofen lysine salt 40 mg granules versus Placebo in male and female subjects with acute pain syndrome after removal of a molar tooth. The patients are assigned to one of two treatment group in 1:1 ratio: * Group 1. OKITASK® 40 mg - 35 patients; * Group 2. Placebo - 35 patients. The study was conducted at 3 Russian sites. A total number of enrolled subjects was 70 (35 per each group). Patients' enrollment was competitive. The study consisted of three periods: screening, study treatment and follow-up. The duration of participation of each subject in the study was to be up to 7±1 days and included: screening (up to 4 days), tooth extraction, randomization and study treatment (1 day), and follow-up (2 days).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Signed Informed Consent Form; 2. Male and female, from 18 years to 65 years (inclusively); 3. Subjects who undergo removal of a non-impacted molar tooth within 3 hours before randomization in the study; 4. Subjects in generally good health (based upon criteria for safe administration of outpatient conscious sedation); 5. Subjects requesting relief for postoperative pain within 3 h after the tooth extraction (VAS ≥30 mm); 6. Subjects willing to undergo observation period for up to 9 hours after the tooth extraction; 7. Ability to complete a 100 mm VAS and a category scale during the observation period (about 9 hours); 8. Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the Investigator and to comply with the requirements of the entire study; 9. Contraception (for females): females of child-bearing potential must be using at least one reliable method of contraception, as follows: 1. hormonal oral, implantable, transdermal, or injectable contraceptives; 2. a non-hormonal intrauterine device \[IUD\] or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide; or should have: 3. a male sexual partner who agrees to use a male condom with spermicide; 4. a sterile sexual partner. Exclusion Criteria: 1. Subjects undergoing extraction of impacted and dystopic teeth, tooth preserving operations, apically positioning flap/vestibuloplasty with free gingival graft from the palate; 2. Subjects undergoing more than one tooth extraction in the same extraction procedure; 3. Subjects undergoing dental implantation simultaneously with tooth extraction; 4. Allergy: ascertained or presumptive hypersensitivity to the active substances (ketoprofen and paracetamol as rescue medication) and/or formulations' ingredients; history of hypersensitivity to drugs (in particular to NSAIDs) or allergic reactions in general, which the Investigator considers may affect the outcome of the study; 5. Diseases: relevant history of renal, hepatic, cardiovascular, respiratory (including asthma), skin, haematological, endocrine, gastro-enteric and genitourinary tract or neurological and autoimmune diseases, that may interfere with the aim of the study; 6. Medications: non-steroidal anti-inflammatory drugs (NSAIDS) and other analgesics \[in particular ketoprofen, paracetamol and acetylsalicylic acid (ASA)\], antihistamines, sedating medications, including herbal and BASs, taken 48 h before surgery; 7. Investigational drug trials: participation in the evaluation of any drug within 3 months before screening (including the last study procedure); 8. Relevant history of drug and alcohol abuse. 9. Positive Pregnancy test in female patients of childbearing potential (including patients in post-menopausal status for less than 2 years).

Outcomes

Primary Outcomes

AUC0-6h of Pain Intensity Between Time 0 (Baseline Value of VAS) and 6 Hours Post-treatment in the ITT Population.

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

AUC0-6h of Pain Intensity Between Time 0 (Baseline Value of VAS) and 6 Hours Post-treatment in the PP Population.

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

Secondary Outcomes

Time Profile of Pain Intensity Using VAS Scale

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.

Time Profile of Pain Relief Using VAS Scale

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.

AUC5min-6h of Pain Relief Profile in the ITT and in the PP Populations

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

Time to First Perceptible Relief (TFPR)

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

Time to Meaningful Pain Relief (TMPR)

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

Number of Participants With an Overall Assessment Score of "Very Good", "Satisfactory", "Poor" or "Very Poor" on a (Patient's Overall Assessment) on a 5-point Scale

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.