Severe pain following impacted third mandibular molar tooth extraction MedDRA version: 14.0 Level: PT Classification code 10033371 Term: Pain System Organ Class: 10018065 - General disorders and administration site conditions
Conditions
Interventions
Product Name: Dexketoprofen trometamol
Product Code: DKP.TRIS
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Dexketoprofen trometamol
CAS Number: 156604-79-4
Current Sponsor code: DKP.TR
Sponsors
Menarini Ricerche S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients meeting ALL the following criteria will be eligible for entry into the study: 1. Male or female patients aged 18 to 70 years. 2. BMI between 18 kg/m2 and 30 kg/m2. 3. Females participating in the study must be either: · Of non-childbearing potential, i.e. surgically sterilised or postmenopausal with amenorrhea for at least 2 years prior the study. If indicated, this should be confirmed by follicle-stimulating hormone and estradiol levels (according to local laboratory range). · Willing to use a highly effective contraceptive method (failure rate 40 mm and VRS score > 2). 14. Patients agreeing not to take analgesics other than protocol defined rescue medication during the treatment period (up to 24 hours post-dosing). Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 600 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Patients will not be eligible to participate in the study if they meet ANY of the following exclusion criteria: 1. Patients with history of allergy or hypersensitivity to the study drugs/rescue medication or to any other NSAIDs, opioids or acetyl salicylic acid. 2. Patients with history of asthma, bronchospasm, acute rhinitis, nasal polyps, uricaria or angioneurotic oedema. 3. Patients with history of peptic ulcer, gastrointestinal disorders by NSAIDs, gastrointestinal bleeding or other active bleedings. 4. Patients with moderate to severe renal, hepatic or cardiac dysfunction. 5. Patients with coagulation disorders. 6. Patients with uncontrolled epilepsy. 7. Patients with Crohn’s disease or ulcerative colitis. 8. Patients with history of drug or alcohol abuse. For the purpose of the study, alcohol abuse is defined as follows for males and females, respectively: - an average weekly intake of >21 and >14 units - or an average daily intake of >3 and >2 units One unit corresponds to approx 125 ml wine, 200 ml beer, 25 ml spirit. 9. Patients who are judged by the investigator not to be suitable candidates for study treatment and rescue medication based on medical history, concomitant medication and concurrent systemic disease as described in the product labelling (i.e. warnings, precaution, contraindication and adverse events) of dexketoprofen, tramadol, ibuprofen and paracetamol. 10. Patients who are unable to refrain from alcohol, psychoactive drugs and sedatives (e.g. benzodiazepines) and other prohibited medication as listed below within 48 hours or 5 half-lives (whichever is the longer) prior to the start of surgery and for 24 hours postdosing. For analgesic use ONLY, a minimum of 24 hours must elapse prior to the start of surgery. For MAO inhibitors, a minimum of 14 days must elapse prior to the start of surgery. Prohibited medication includes the following: o Analgesic drugs (other NSAIDs and opioids). o Anticoagulants, thrombolytic and antiplatelet agents. o Corticosteroids. o MAO inhibitors. o Antiepileptic drugs. o Antipsychotics. o Serotonin reuptake inhibitors and tricyclic antidepressants. o Lithium. o Metotrexate. o Sulphonamides. 11. Patients using and not suitable for withdrawing other prescription or non prescription drugs which are expected to interfere with the study treatment and procedures or compromise patient safety as described in the product labelling of study treatments/rescue medication, within 48 hours or 5 half-lives (whichever is the longer) prior to the start of surgery and for 24 hours post-dosing. 12. Patients receiving concomitant treatment with other investigational drugs or who have participated in other clinical trial within 4 weeks before the study enrolment. 13. Pregnant or breastfeeding women. A pregnancy test will be performed to all women of childbearing potential at the Screening and Randomisation Visits and a negative result must be obtained to enroll the patient into the study. 14. Patients who are not able to understand the study nature for any reason (e.g. cultural level, language comprehension) or that the investigator suspects that they are not going to collaborate with the study procedures (e.g. patients with excessive anxiety related to previous negative dental experiences). 15. Patients with a history of any illness or condition that, in the opinion of the investigator, might pose a risk to the patient or confound the results of the study (e.g. patients with
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the analgesic efficacy of DKP.TRIS and TRAM.HCl given as fixed combinations and the analgesic efficacy of each single component in comparison to placebo on moderate to severe pain following impacted third mandibular molar tooth extraction. Ibuprofen will be used as an active control to validate the pain model.;Secondary Objective: · To assess the safety and tolerabilility of the administration of 4 different combination doses of DKP.TRIS with TRAM.HCl up to 25 mg + 75 mg, respectively, on moderate to severe pain following impacted third mandibular molar tooth extraction. · To make an overall assessment of efficacy and tolerability in order to select the optimum dose(s) to be tested in the subsequent phase III pivotal studies.;Primary end point(s): Percentage of patients showing response, which is defined as at least 50% max TOTPAR, over 6 hours post-dosing period (where max TOTPAR corresponds to the theoretical maximum PAR scores on the 5-point VRS), within the respective treatment arm.;Timepoint(s) of evaluation of this end point: Prior to unblinding of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Percentage of patients experiencing at least 50% max TOTPAR over 4, 8 and 12 hours post-dosing period. 2. TOTPAR (Total pain relief), calculated as the weighted sum of the PAR scores over 4, 6, 8 and 12-hours post-dosing period (TOTPAR 4, TOTPAR 6, TOTPAR 8, TOTPAR 12). 3. % max TOTPAR over 4, 6, 8 and 12-hour post-dosing period. 4. Mean PAR scores over 24-hour post-dosing period. 5. SPID (Sum of Pain Intensity Differences), calculated as the weighted sum of the PID values obtained from the four-point VRS, over the 4, 6, 8 and 12-hour post-dosing period (SPID 4, SPID 6, SPID 8, SPID 12). 6. % max SPID, over the 4, 6, 8 and 12-hour post-dosing period. 7. Mean Pain Intensity (PI) scores over the 24-hour post-dosing period. 8. Patient’s Global Evaluation from the five-point categorical VRS (1 = poor, 2 = fair, 3 = good, 4 = very good, 5 = excellent), at 24h or whenever the patient uses rescue medication (or withdraws from the study). 9. Time to use of rescue medication (RM): Time elapsed between treatment administration and intake of first rescue medication. 10. Percentage of patients who require rescue medication at 4, 6, 8, 12 and 24 h point-time.;Timepoint(s) of evaluation of this end point: Prior to unblinding of the study | — |
Countries
Germany, Hungary, Italy, Poland, Spain, United Kingdom
Outcome results
None listed