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

Study Overview
=================
Brief Summary
-----------------
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)

Detailed Description
-----------------
This is a multicenter, double blind, randomised, 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 molar teeth.

Official Title
-----------------
A Multicenter, Double Blind, Randomised, Parallel Study to Assess Efficacy and Tolerability After Single Administration of Ketoprofen Lysine Salt 40 mg Granules vs Placebo in Subjects With Acute Pain Syndrome After Removal of Molar Teeth

Conditions
-----------------
Acute Pain

Intervention / Treatment
-----------------
* Drug: Ketoprofen
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed Informed Consent Form; Male and female, from 18 years to 65 years (inclusively); Subjects who undergo removal of a non-impacted molar tooth within 3 hours before randomization in the study; Subjects in generally good health (based upon criteria for safe administration of outpatient conscious sedation); Subjects requesting relief for postoperative pain within 3 h after the tooth extraction (VAS ≥30 mm); Subjects willing to undergo observation period for up to 9 hours after the tooth extraction; Ability to complete a 100 mm VAS and a category scale during the observation period (about 9 hours); 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; Contraception (for females): females of child-bearing potential must be using at least one reliable method of contraception, as follows: hormonal oral, implantable, transdermal, or injectable contraceptives; 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: a male sexual partner who agrees to use a male condom with spermicide; a sterile sexual partner. Exclusion Criteria: Subjects undergoing extraction of impacted and dystopic teeth, tooth preserving operations, apically positioning flap/vestibuloplasty with free gingival graft from the palate; Subjects undergoing more than one tooth extraction in the same extraction procedure; Subjects undergoing dental implantation simultaneously with tooth extraction; 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; 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; 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 beforesurgery; Investigational drug trials: participation in the evaluation of any drug within 3 months before screening (including the last study procedure); Relevant history of drug and alcohol abuse. Positive Pregnancy test in female patients of childbearing potential (including patients in post-menopausal status for less than 2 years).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketoprofen<br>Single oral administration of Ketoprofen lysine salt 40 mg granules | Drug: Ketoprofen<br>* 40 mg KLS granules (corresponding to 25 mg ketoprofen)<br>* Other names: Okitask, ketoprofen lysine salt (KLS);|
| Placebo Comparator: Placebo<br>Single oral administration of placebo granules | Other: Placebo<br>* 0 mg KLS granules<br>* Other names: Control;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-6h of pain profile | Pain will be assessed 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. | From time 0 (baseline value of VAS) to 6 hours post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time profile of pain. | Pain will be assessed by a horizontal 100 mm Visual Analogue Scale (VAS): 0 no pain - 100 worst pain imaginable. | From time 0 (baseline value of VAS) to 6 hours post-treatment at: 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) after the drug administration. | 
| Time profile of pain relief | Pain relief will be assessed by a horizontal 100 mm VAS: 0 no relief - 100 maximum relief. | From time 0 (baseline value of VAS) to 6 hours post-treatment at: 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. | 
| Time to first perceptible relief (TFPR) | TFPR will be measured by stopwatches. Upon study drug administration the patients will immediately start a stopwatch, once the patient feels first perceptible pain relief. | Day 1 | 
| Time to meaningful pain relief (TMPR) | TFPR will be measured by stopwatches. Upon study drug administration the patients will immediately start a stopwatch, once the patient feels first perceptible pain relief. | Day 1 | 
| Proportion of patients requiring rescue medication (analgesia) | Should the patient require rescue medication at any time during 6 hours post-dose, the last VAS measurement and patient's overall assessment will be performed before the rescue medication dosing. Subjects will be encouraged to postpone the rescue medication until after 1 hour post-dose. | Day 1 | 
| Time to rescue analgesia | In the event of poor pain control, subjects will be allowed access to rescue medication for analgesia (Paracetamol 500-1000 mg). Time to REMD (rescue) with an alternative analgesic, if it occurred, will be recorded. Subject will be encouraged to postpone the rescue medication until after 1 h post dose. If Paracetamol 500-1000 mg is not effective, the patient will be allowed to take another dose of Paracetamol 500-1000 mg every 6-8 hours; maximum daily dose is 4000 mg. | Day 1 | 
| Patient's overall assessment | Patient's overall assessment (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. | Day 1 at 360' or > 60' in case of early discontinuation. |