Symptomatic short-term treatment of moderate pain MedDRA version: 20.0 Level: LLT Classification code 10036286 Term: Post-operative pain System Organ Class: 100000004863 MedDRA version: 20.0 Level: LLT Classification code 10059723 Term: Tooth pain System Organ Class: 100000004856
Conditions
Interventions
Product Name: Paracetamol UNIFLASH
Product Code: [08P1703F0]
Pharmaceutical Form: Oromucosal/laryngopharyngeal solution
INN or Proposed INN: PARACETAMOLO
Current Sponsor code: NA
Concentration unit: m
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. 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 |
|---|---|
| Main Objective: To evaluate the efficacy, after one single administration, of 125 mg of a new paracetamol form for buccal use (paracetamol UNIFLASH) in patients with a moderate pain after tooth extraction in terms of: 1. Superiority on the pain intensity reduction (Sum of Pain Intensity Difference – SPID0-60min) at 1 hour versus placebo; 2. Non-inferiority on the onset of pain relief versus 500 mg of the reference oral paracetamol (Panadol®); 3. Non-inferiority on the number and proportion of responder patients at 1 hour versus 500 mg of the reference oral paracetamol (Panadol®); 4. Non-inferiority on the Subject's global evaluation (Patient Global Impression of Change - PGIC) of the treatment at 1 hour versus 1000 mg of the reference oral paracetamol (Panadol®); 5. Non-inferiority on the onset of pain relief versus 1000 mg of the reference oral paracetamol (Panadol®).;Secondary Objective: Evaluate the non-inferiority in term of efficacy after 1 single administration of 125 mg of a new paracetamol form for buccal use paracetamol UNIFLASH vs 2 oral paracetamol at different time-points in patients with a moderate pain after tooth extraction on: 1) pain intensity reduction at 5,10,30,45mn, 1,2,4,6 h vs 500 & 1000 mg of oral paracetamol 2) number and proportion of responder patients at 1 h vs 1000 mg of oral paracetamol 3) number and proportion of responder patients at 5,10,30,45mn;2, 4,6h vs 500 & 1000 mg of oral paracetamol 4) Pain Relief at 1,2,4,6h vs 500 mg and 1000 mg of oral paracetamol 5) Duration of pain relief throughout 6 h vs 500 & 1000 mg of oral paracetamol 6) Subject's global evaluation of the treatment at 1 h vs 500 mg of oral paracetamol 7) Subject's global evaluation of the treatment at 6 h vs 500 mg and 1000mg of oral paracetamol;Primary end point(s): 1. 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 t | — |
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 relief, | — |
Countries
France, Italy, Poland, Spain
Contacts
Public ContactInnovation and Development Director
Unither Pharmaceuticals
Outcome results
None listed