Symptomatic short-term treatment of moderate pain
Conditions
Interventions
Product Name: Paracetamol UNIFLASH
Product Code: 08P1703F0
Pharmaceutical Form: Oromucosal solution
Pharmaceutical form of the placebo: Oromucosal solution
Route of administration of the placebo: Bucc
Sponsors
UNITHER Pharmaceuticals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female patient aged from 18 years of age at the time of signing the informed consent; 2. Patient scheduled to undergo the removal of one third soft-tissue impacted or not-impacted mandibular molar (associated or not to an ipsilateral erupted maxillary molar) under short-acting local anaesthetic (e.g., mepivacaine or lidocaine) preoperatively; 3. Patient weighing > 50 kg; 4. Female patient of childbearing potential must be willing to use a highly efficient birth control method during the study; A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The following are considered as highly effective birth control methods : Established use of oral, intravaginal or transdermal combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation - Established use of oral, injected, or implanted progestogen-only hormonal contraception associated with inhibition of ovulation – Intrauterine hormone-releasing system or placement of an intrauterine device – Bilateral tubal occlusion – Vasectomised partner - True abstinence [periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception]. 5. Patient able to understand and comply with protocol requirements and instructions; 6. Patient covered by national healthcare insurance system or similar system, if applicable by local regulations; 7. Patient who has signed a written informed consent obtained prior to any study-related procedures. Additional inclusion criteria after surgery (randomization): 1. Patients experiencing a moderate pain within 4 hours after the dental extraction, defined by a baseline pain intensity Visual Analogic Scale (VAS) score = 40 mm and = 60 mm; 2. Third mandibular molar extraction completed without any immediate complication, that in the opinion of the investigator, would interfere with the study conduct and/or assessments (e.g., suspected neurosensory complication, incomplete removal of tooth). 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 400 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: 1. Patient who undergoes an extraction of contralateral molar in the same procedure or a bony-impacted molar; 2. Patient treated by analgesics or nonsteroidal anti-inflammatory drugs (NSAIDs) within the 3 days prior to the day of randomization (or within 5 times the elimination half-life whichever the longest); 3. Patient who received other analgesic than short-acting preoperative or intraoperative local anaesthetic agents within 12 hours before the start of the surgery or peri-operatively until randomization; 4. Patient with any known hypersensitivity to paracetamol, ibuprofen or ingredients contained in Investigational Medicinal Products (IMP) and Non-Investigational Medicinal Products (NIMP); 5. Patient with contra-indication to the alcoholic solution for medical reason (alcoholic weaning or abuse, epilepsy); 6. Women with positive results on a urine pregnancy test or breastfeeding women or women of childbearing potential without an effective contraception; 7. Patient with current or chronic history of liver disease, or known hepatic or biliary abnormalities; 8. Patient with a current or chronic history of severe renal impairment; 9. Patient with severe heart failure (New York Heart Association (NYHA) Class IV); 10. Patient with history of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy; 11. Patient with gastrointestinal haemorrhage, cerebrovascular haemorrhage or of other evolving haemorrhage; 12. Patient with an active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding); 13. Patient with inflammation or ulcerative disease of the oral mucosa (i.e., aphthae…); 14. Patient with known systemic lupus erythematosus; 15. Patient having developed hypersensitivity reactions, including symptoms of asthma, rhinitis, angioedema or urticaria after taking acetylsalicylic acid or other NSAIDs; 16. Patient with drug or alcohol abuse within 6 months before dosing with study medication; Alcohol abuse is defined as the consumption of more than 90 mL of liquor or spirits or 530 mL of beer per day, for 5 consecutive days during the 6-month period. Drug abuse is defined as the use of any recreational drug for 5 consecutive days during the 6-month period. 17. Patient having participated in any clinical research study within the previous 30 days or 5 half-lives duration of the biological effect of the investigational product (whichever is longer); 18. Patient having any current dental or medical condition that could prevent safe participation in this study; 19. Unwillingness or inability to follow the procedures outlined in the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Sum of Pain Intensity Difference (SPID0-60min) over 60 minutes (1 hour) post-IMP intake. SPID0-60min: Time-weighted summary measure of the total area under the pain intensity difference (PID) curve that integrates serial assessments of pain during the first hour after IMP intake. PID will be calculated using the scores of pain intensity assessed by the patient at defined time-points (T5, T10, T15, T20, T30, T45, T60 min) after the IMP intake and/or right before first intake of rescue medication using a 100-mm VAS (0= no pain and 100= worst imaginable pain; see Appendix 17.1 ) compared to baseline. 2. Onset of pain relief (versus 500 mg of the reference oral paracetamol (Panadol®) Defined as the period for the patient to reach a meaningful pain relief during the first 60 min post-IMP intake. After completion of the 5-point verbal rating scale (VRS) (0- no relief, 1- little relief, 2- some relief, 3- a lot of relief, 4- complete relief of pain; see Appendix 17.2) at T5, T10, T15, T20,T30, T45, T60 min post-IMP intake assessment time-points, the patient will have to answer this question "Do you consider this level of pain relief as meaningful - Yes or No?" 3. Number and proportion of responder patients at 60 minutes (versus 500 mg of the reference oral paracetamol (Panadol®)). A responder patient is defined as a subject who achieves a reduction of 50 % of pain intensity compared to baseline. 4. Patient Global Impression of Change (PGIC) versus 1000 mg of the reference oral paracetamol (Panadol®): assessed at T60 min post-IMP intake or at time of rescue medication (whichever happens first). 5. Onset of pain relief (versus 1000 mg of the reference oral paracetamol (Panadol®)). Defined as the period for the patient to reach a meaningful pain relief during the first 60 min post-IMP intake. After completion of the a 5-point verbal rating scale (0- no relief, 1- little relief, 2- some relief, 3- a lot of relief, 4- complete relief of pain; see Appendix | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Sum of Pain Intensity Difference at 5 min (SPID0-5min), 10 min (SPID0-10min), 30 min (SPID0-30min), 45 min (SPID0-45min), 1 hour (SPID0-1h), 2 hour (SPID0-2h), 4 hour (SPID0-4h), and 6 hours (SPID0-6h). SPID: time-weighted summary measure of the total area under the pain intensity difference (PID) curve that integrates serial assessments of pain during the first 5 min, 10 min, 30 min, 45 min, 1 hour, 2 hours, 4 hours and then 6 hours after the IMP intake. PID will be calculated using the score of pain intensity assessed by the patient at defined time-points (T5, T10, T15, T20, T30, T45, T90, T120, T180, T240, T300 and T360 min) after IMP intake or right before first intake of rescue medication using a 100-mm VAS compared to baseline. · Number and proportion of responders at 60 minutes (versus 1000 mg of the reference oral paracetamol (Panadol®)). A responder patient is defined as a subject who achieves a reduction of 50 % of pain intensity compared to baseline. · Number and proportion of responders at 5 min, 10 min, 30 min, 45 minutes, 2 hours, 4 hours and then 6 hours. A responder patient is defined as a subject who achieves a reduction of 50 % of pain intensity compared to baseline at each time point of the study. · Total Pain Relief at 1 hour (TOTPAR0-1h), 2 hours (TOTPAR0-2h), 4 hours (TOTPAR0-4h) and 6 hours (TOTPAR0-6h), measured with a 5-point verbal rating scale (none – a little – some – lot – complete pain relief; see Appendix 2). TOTPAR: time-weighted summed measure of the total area under the pain relief (PAR) curve that integrates serial assessments of pain during the first 1 hour, 2 hours, 4 hours and then 6 hours after the IMP intake. Pain relief (PAR) will be assessed by the patient at defined time points (T5, T10, T15, T20,T30, T45, T60, T90, T120, T180, T240, T300 and T360 min) after IMP intake and/or right before first intake of rescue medication using a 5-point verbal rating scale (0- no relief, 1- little relief, 2- some re | — |
Countries
France
Contacts
Public ContactInnovation and Development Director
UNITHER Pharmaceuticals
Outcome results
None listed