Clinical trial NCT03836807: A Study to Assess Efficacy and Tolerability of Ketoprofen 40 mg Granules vs Placebo
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Pain
Keywords: dental pain
neuralgia
Lead sponsor: Dompé Farmaceutici S.p.A
Sponsor class: INDUSTRY
First posted: 2019-02-11
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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, 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).

Eligibility criteria: 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).

Primary outcomes:
measure: AUC0-6h of Pain Intensity Between Time 0 (Baseline Value of VAS) and 6 Hours Post-treatment in the ITT Population.
timeFrame: 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
measure: AUC0-6h of Pain Intensity Between Time 0 (Baseline Value of VAS) and 6 Hours Post-treatment in the PP Population.
timeFrame: 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:
measure: Time Profile of Pain Intensity Using VAS Scale
timeFrame: 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.
measure: Time Profile of Pain Relief Using VAS Scale
timeFrame: 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.
measure: AUC5min-6h of Pain Relief Profile in the ITT and in the PP Populations
timeFrame: from 5 min to 6 hours post-dose
measure: Time to First Perceptible Relief (TFPR)
timeFrame: Day 1
measure: Time to Meaningful Pain Relief (TMPR)
timeFrame: Day 1
measure: 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
timeFrame: Day 1 at 360' or > 60' in case of early discontinuation.
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: LLC "Centre for Interdisciplinary Dentistry and Neurology"
city: Moscow
country: Russian Federation
facility: Federal State Educational Institution "Moscow State Medical Dental University named after Yevdokimov "of the Russian Federation Ministry of Health
city: Yaroslavl
country: Russian Federation
facility: State Autonomous Healthcare Institution of Yaroslavl Region "Clinical Hospital of Emergency care n.a. N.V. Solovyev"
Study officials:
affiliation: Dompé SpA Milan
name: Luigi Lanata, MD
role: STUDY_DIRECTOR
References: