moderate to severe acute pain after removal of impacted lower third molar MedDRA version: 18.1 Level: LLT Classification code 10066714 Term: Acute pain System Organ Class: 100000004867
Conditions
Interventions
Product Name: DEXKETOPROFEN TROMETAMOL - TRAMADOL HYDROCHLORIDE
Product Code: DKP.TRIS/TRAM.HCl
Pharmaceutical Form: Film-coated tablet
INN or Proposed
Sponsors
MENARINI RICERCHE S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Properly executed written informed consent. 2. Male or female patients aged more than 18 years. 3. Scheduled for outpatient surgical extraction -under local anaesthesia (i.e. 2% lidocaine with 1:80,000 epinephrine) - of lower third molar teeth, with at least one of which fully or partially impacted in the mandible requiring bone manipulation (e.g. level B or C plus class II or III of the Pell-Gregory scale). 4. Females participating in the study must be either: - Females of non-childbearing potential, defined as any woman who had undergone surgical sterilization or is more than 2 years post-menopausal; - Females of childbearing potential provided that they have a negative pregnancy test at baseline (screening and qualification period) and are routinely using an effective method of birth control resulting in a low failure rate (i.e. hormonal contraception, intrauterine device, condoms in combination with a spermicidal cream, male partner sterilization –vasectomy– or total sexual abstinence). 5. Mentally competent, able to understand and give written informed consent prior to study entry. 6. Compliant to undergo all visits and procedures scheduled in the study, including recording of pain assessments on the electronic diary (e-Diary) as required by protocol. After surgery, patients will be eligible to progress with randomisation ONLY if the following criterion is also met: 7. Pain of at least moderate intensity in the first 4 hours after the end of surgery (NRS score >= 4). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 630 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Patients who are judged by the Investigator not to be suitable candidates for the study treatments and the RM based on their medical history, physical examination, concomitant medication (CM) and concurrent systemic diseases. 2. Clinically significant abnormalities in the vital signs (VS) and / or safety laboratory tests, as per investigator’s judgement. 3. History of allergy or hypersensitivity to the study treatments, RM or to any other NSAIDs, opioids and acetyl salicylic acid. 4. History of peptic ulcer, gastrointestinal disorders by NSAIDs or gastrointestinal bleeding or other active bleedings. 5. History of severe asthma. 6. Moderate to severe renal dysfunction, severe hepatic dysfunction or severe cardiac dysfunction. 7. Coagulation disorders. 8. History of, or current epilepsy. 9. Patients with Crohn’s disease or ulcerative colitis. 10. Patients using and not suitable for withdrawing analgesics within 12 hours before surgery (5 days prior to the surgery day in case of COX-2 inhibitors) and for 8 hours post-dose [analgesics other than those specified in the protocol (namely study treatments and RM)]. 11. Patients using and not suitable for withdrawing alcohol, sedatives (e.g. benzodiazepines) and hypnotic agents within 12 hours before surgery and for 8 hours post-dose. 12. Chronic opioid treatment (major opioids and tramadol). 13. Patients using and not suitable for withdrawing the following prohibited medications, within 48 hours or 5 half-lives (whichever the longer) prior to the start of surgery and for 24 hours post-dose: - Anticoagulants, thrombolytic and antiplatelet agents - Corticosteroids (with the exception of inhalers or topical agents); - Monoamine oxidase (MAO) inhibitors (a minimum of 14 days must elapse prior to the start of surgery); - Antiepileptics; - Antipsychotics; - Serotonin reuptake inhibitors and tricyclic antidepressants; - Lithium; - Methotrexate; - Antibacterial sulfonamides. 14. Participation in other clinical studies in the previous 4 weeks. 15. History of drug or alcohol abuse. For the purpose of the study, alcohol abuse is defined as regularly intake of more than 4 units of alcohol per day (1 unit corresponds approximately to 125 ml wine, 200 ml beer, 25 ml spirit). 16. History of any illness or condition that, in the opinion of the Investigator might pose a risk to the patient or confound the efficacy and safety results of the study. 17. Pregnant and breastfeeding women. NOTE: a pregnancy test will be performed to all women of childbearing potential at Screening and another one on the day of surgery prior to randomisation. After surgery, patients will not be eligible to progress with randomisation if the following criterion is also met: 18. Surgical complication that, in the opinion of the Investigator, advises against their inclusion in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the comparability of DKP.TRIS/TRAM.HCl and TRAM.HCl/paracetamol in terms of analgesic efficacy on moderate to severe pain following impacted lower third molar extraction.;Secondary Objective: To confirm the safety and tolerability profile of DKP.TRIS/TRAM.HCl following single dose administration.; Primary end point(s): Total pain relief (TOTPAR), calculated as the weighted sum of the PAR scores (measured according to a 5-point VRS from 0=no relief to 4=complete relief) over 6 hours post-dose (TOTPAR6) ;Timepoint(s) of evaluation of this end point: over 6 hours post-dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficay Endpoints: - Mean PAR scores over the 8-hour post-dose period. - TOTPAR over 4 and 8 hours post-dose (TOTPAR4, TOTPAR8). - Percentage of maximum TOTPAR (% max TOTPAR) over 4, 6 and 8- hours post-dose. - Percentage of patients achieving at least 50% of maximum TOTPAR over 4, 6 and 8 hours post-dose. - Mean Pain Intensity (PI) scores (values obtained from the 11-point NRS) at each pre-specified time point over the 8-hour post-dose period. - Percentage of patients who achieved at least 30% of PI reduction versus baseline at each pre-specified time point over the 8-hour post-dose period. - Sum of Pain Intensity Differences (SPID), calculated as the weighted sum of the pain intensity difference (PID) over 4, 6 and 8 hours postdose (SPID4, SPID6, SPID8). - Percentage of maximum SPID (% max SPID) over 4, 6 and 8 hours post-dose. - Time to FPPAR (time to onset of analgesia). - Time to confirmed FPPAR (time to onset of analgesia) - i.e. time to FPPAR if confirmed by experiencing MPAR - Percentage of patients who achieved confirmed FPPAR within 30 minutes, 1 hour and 2 hours. - Time to MPAR. - Percentage of patients who achieved MPAR within 30 minutes, 1 hour and 2 hours. - PGE of the study medication (measured according to a five-point VRS from 1 = poor to 5 = excellent), at 8 hours post-dose or whenever the patient uses RM. - Time to RM: Time elapsed between treatment administration and first intake of RM. - Percentage of patients who required RM within the first 4, 6 or 8 hours post-dose. Safety endpoints: a) Incidence, intensity (severity), seriousness and treatment-causality of treatment-emergent AEs | — |
Countries
Hungary, Italy, Poland, Spain, Turkey, United Kingdom
Contacts
Public ContactCl. Research Corporate Director
Menarini Ricerche S.p.A.
Outcome results
None listed