A Study to Assess Efficacy and Tolerability of Ketoprofen 40 mg Granules vs Placebo (KSL0117)

• ClinicalTrials.gov Identifier: NCT03836807
• Recruitment Status: Completed
• First Posted: February 11, 2019
• Last Update Posted: February 11, 2019
• Sponsor: Dompé Farmaceutici S.p.A
• Information provided by (Responsible Party): Dompé Farmaceutici S.p.A

Study Description

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)

Condition or disease	Intervention/treatment	Phase
Acute Pain	Drug: Ketoprofen; Other: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)

Masking Description

The double-blinding is provided by Placebo that is identical to OKITASK® 40 mg granules.

The drug will be packaged and labeled in a manner that will exclude unblinding.IWRS will assign the study drug kit number that should be administrated by the subject.

• Primary Purpose: Treatment
• 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
• Actual Study Start Date: April 4, 2018
• Actual Primary Completion Date: July 24, 2018
• Actual Study Completion Date: December 21, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ketoprofen; Single oral administration of Ketoprofen lysine salt 40 mg granules	Drug: Ketoprofen; 40 mg KLS granules (corresponding to 25 mg ketoprofen); Other Name: Okitask, ketoprofen lysine salt (KLS)
Placebo Comparator: Placebo; Single oral administration of placebo granules	Other: Placebo; 0 mg KLS granules; Other Name: Control

Outcome Measures

Primary Outcome Measures :

1. AUC0-6h of pain profile [ Time Frame: From time 0 (baseline value of VAS) to 6 hours post-treatment ]
   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.

Secondary Outcome Measures :

1. Time profile of pain. [ Time Frame: 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. ]
   Pain will be assessed by a horizontal 100 mm Visual Analogue Scale (VAS): 0 no pain - 100 worst pain imaginable.
2. Time profile of pain relief [ Time Frame: 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. ]
   Pain relief will be assessed by a horizontal 100 mm VAS: 0 no relief - 100 maximum relief.
3. Time to first perceptible relief (TFPR) [ Time Frame: Day 1 ]
   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.
4. Time to meaningful pain relief (TMPR) [ Time Frame: Day 1 ]
   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.
5. Proportion of patients requiring rescue medication (analgesia) [ Time Frame: Day 1 ]
   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.
6. Time to rescue analgesia [ Time Frame: Day 1 ]
   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.
7. Patient's overall assessment [ Time Frame: Day 1 at 360' or > 60' in case of early discontinuation. ]

   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 beforesurgery;
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).

Contacts and Locations

Locations

Russian Federation

LLC "Centre for Interdisciplinary Dentistry and Neurology"

Moscow, Russian Federation, 119146

Federal State Educational Institution "Moscow State Medical Dental University named after Yevdokimov "of the Russian Federation Ministry of Health

Moscow, Russian Federation, 127473

State Autonomous Healthcare Institution of Yaroslavl Region "Clinical Hospital of Emergency care n.a. N.V. Solovyev"

Yaroslavl, Russian Federation

Sponsors and Collaborators

Dompé Farmaceutici S.p.A

Investigators

• Study Director: Mauro P. Ferrari, Pharm D; Dompé SpA Milan

More Information

• Responsible Party: Dompé Farmaceutici S.p.A
• ClinicalTrials.gov Identifier: NCT03836807
• Other Study ID Numbers: KSL0117
• First Posted: February 11, 2019
• Last Update Posted: February 11, 2019
• Last Verified: May 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Acute Pain; Pain; Neurologic Manifestations; Ketoprofen; Ketoprofen lysine; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action