INTERVENTION: Product Name: Ibalgin Extra Fast Pharmaceutical Form: Coated tablet CAS Number: 57469‐77‐9 Other descriptive name: ibuprofen lysinate Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 684‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Trade Name: Nurofen Forte Product Name: Nurofen Forte Pharmaceutical Form: Coated tablet INN or Proposed INN: ibuprofen CAS Number: 15687‐27‐1 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 400‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: subject is indicated for outpatient surgical removal of one or more third molars, at least one of which is impacted in bone ; MedDRA version: 9.1 Level: LLT Classification code 10028819 Term: Nausea vomiting and diarrhea ; MedDRA version: 9.1 Level: LLT Classification code 10019211 Term: Headache ; MedDRA version: 9.1 Level: LLT Classification code 10017822 Term: Gastric ulcer INCLUSION CRITERIA: • Written informed consent obtained • Subject is indicated for outpatient surgical removal of one or more third molars, at least one of which is impacted in bone • Subjects between 18 – 60 years, both sexes • Negative pregnancy test in females with childbearing potential • Subject agrees not to take analgesics other than protocol defined rescue analgesics during treatment, anti‐inflammatory drugs, sedative‐hypnotics, or antidepressants, tranquilizers, alcohol or caffeine‐containing beverages up to 6 hrs post dose • Ability to read, comprehend, and record information required by protocol. 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 F.1.3 Elderly (>=65 years) F.1.3.1 Number of subjects for this age range PRIMARY OUTCOME: Main Objective: To demonstrate that:; 1. Ibalgin Extra Fast® is superior over placebo in overall analgesic efficacy.; This conclusion will be drawn if and only if the lower limit of the two‐sided 95% confidence interval for the treatment difference (test‐placebo) in TOTPAR is greater than zero.; 2. Ibalgin Extra Fast® is non‐inferior to Nurofen forte® (the active comparator) in overall analgesic efficacy.; This conclusion will be drawn if and only if 1. is concluded and two‐sided 95% confidence interval for the treatment difference (test‐active comparator) in TOTPAR lies entirely to the right of the non‐inferiority margin.; 3. Ibalgin Extra Fast® is superior over Nurofen forte® (the active comparator) in the onset of action.; This conclusion will be drawn if and only if 2. is concluded and the lower limit of the two‐sided 95% confidence interval for the treatment difference (test‐active comparator) in PAR45 is greater than zero.; Primary end point(s): To demonstrate that:; 1. Ibalgin Extra Fast® is superior over placebo in overall analgesic efficacy.; This conclusion will be drawn if and only if the lower limit of the two‐sided 95% confidence interval for the treatment difference (test‐placebo) in TOTPAR is greater than zero.; 2. Ibalgin Extra Fast® is non‐inferior to Nurofen forte® (the active comparator) in overall analgesic efficacy.; This conclusion will be drawn if and only if 1. is concluded and two‐sided 95% confidence interval for the treatment difference (test‐active comparator) in TOTPAR lies entirely to the right of the non‐inferiority margin.; 3. Ibalgin Extra Fast® is superior over Nurofen forte® (the active comparator) in the onset of action.; This conclusion will be drawn if and only if 2. is concluded and the lower limit of the two‐sided 95% confidence interval for the treatment difference (test‐active comparator) in PAR45 is greater than zero.; Secondary Objective: To assess Superiority of Nurofen forte® (the active comparator) over placebo in TOTPAR; (to demonstrate assay sensitivity), Global Assessment of Medication , Remedication time, Time to pain half gone, Time to any pain relief, Time to meaningful pain relief, Sum of Pain Intensity Difference (SPID), Safety ;
INTRODUCTION: Ibuprofen acid is poorly soluble in the stomach, thus reaching maximum plasma levels at approximately 90 min post-dose. Ibuprofen lysinate has been developed to accelerate absorption of ibuprofen to shorten the time to analgesic efficacy. This study compared analgesic efficacy and onset of effect of a single dose of ibuprofen lysinate or ibuprofen acid in patients undergoing third molar extraction.
METHODS: Randomized, double-blind, placebo-controlled, multi-center, parallel-group single-dose study. Adults (18-60 years) undergoing extraction of ≥ 1 third molar were randomized 2:2:1 to ibuprofen lysinate, ibuprofen acid, or placebo postoperatively. Pain relief (PAR, 5-point scale, 0 = none to 4 = complete pain relief) and pain intensity (PI, 100 mm visual analog scale) were assessed between 15 and 360 min post-dose. The primary endpoint was the weighted sum of PAR scores at 6 h (TOTPAR). Time to onset of effect, global assessment of efficacy, and adverse events were also assessed.
RESULTS: Overall, 351 patients received ibuprofen lysinate (N = 141), ibuprofen acid (N = 139), or placebo (N = 71). Both active treatments significantly reduced pain compared with placebo, from 15 min post-dose to 6 h (TOTPAR: ibuprofen lysinate: 19.57; ibuprofen acid: 19.96; placebo: 8.27). Ibuprofen lysinate was significantly more effective than placebo, but non-inferior to ibuprofen acid, at providing pain relief over 6 h. There was no significant difference between ibuprofen lysinate and ibuprofen acid for onset of analgesia. Both ibuprofen formulations were well tolerated; all adverse events were mild to moderate and considered unrelated to treatment.
CONCLUSIONS: A single dose of ibuprofen lysinate is non-inferior to ibuprofen acid in terms of analgesic efficacy, onset of action, and tolerability in patients who have recently undergone dental surgery.
TRIAL REGISTRATION: EudraCT No. 2006-006942-33. Plain language summary available for this article.
Product Name: Ibalgin Extra Fast Pharmaceutical Form: Coated tablet CAS Number: 57469‐77‐9 Other descriptive name: ibuprofen lysinate Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 684‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Trade Name: Nurofen Forte Product Name: Nurofen Forte Pharmaceutical Form: Coated tablet INN or Proposed
INN:
ibuprofen CAS Number: 15687‐27‐1 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 400‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use
CONDITION:
subject is indicated for outpatient surgical removal of one or more third molars, at least one of which is impacted in bone ; MedDRA version: 9.1 Level: LLT Classification code 10028819 Term: Nausea vomiting and diarrhea ; MedDRA version: 9.1 Level: LLT Classification code 10019211 Term: Headache ; MedDRA version: 9.1 Level: LLT Classification code 10017822 Term: Gastric ulcer
INCLUSION CRITERIA:
• Written informed consent obtained • Subject is indicated for outpatient surgical removal of one or more third molars, at least one of which is impacted in bone • Subjects between 18 – 60 years, both sexes • Negative pregnancy test in females with childbearing potential • Subject agrees not to take analgesics other than protocol defined rescue analgesics during treatment, anti‐inflammatory drugs, sedative‐hypnotics, or antidepressants, tranquilizers, alcohol or caffeine‐containing beverages up to 6 hrs post dose • Ability to read, comprehend, and record information required by protocol. 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 F.1.3 Elderly (>=65 years) F.1.3.1 Number of subjects for this age range
PRIMARY OUTCOME:
Main Objective: To demonstrate that:; 1. Ibalgin Extra Fast® is superior over placebo in overall analgesic efficacy.; This conclusion will be drawn if and only if the lower limit of the two‐sided 95% confidence interval for the treatment difference (test‐placebo) in TOTPAR is greater than zero.; 2. Ibalgin Extra Fast® is non‐inferior to Nurofen forte® (the active comparator) in overall analgesic efficacy.; This conclusion will be drawn if and only if 1. is concluded and two‐sided 95% confidence interval for the treatment difference (test‐active comparator) in TOTPAR lies entirely to the right of the non‐inferiority margin.; 3. Ibalgin Extra Fast® is superior over Nurofen forte® (the active comparator) in the onset of action.; This conclusion will be drawn if and only if 2. is concluded and the lower limit of the two‐sided 95% confidence interval for the treatment difference (test‐active comparator) in PAR45 is greater than zero.; Primary end point(s): To demonstrate that:; 1. Ibalgin Extra Fast® is superior over placebo in overall analgesic efficacy.; This conclusion will be drawn if and only if the lower limit of the two‐sided 95% confidence interval for the treatment difference (test‐placebo) in TOTPAR is greater than zero.; 2. Ibalgin Extra Fast® is non‐inferior to Nurofen forte® (the active comparator) in overall analgesic efficacy.; This conclusion will be drawn if and only if 1. is concluded and two‐sided 95% confidence interval for the treatment difference (test‐active comparator) in TOTPAR lies entirely to the right of the non‐inferiority margin.; 3. Ibalgin Extra Fast® is superior over Nurofen forte® (the active comparator) in the onset of action.; This conclusion will be drawn if and only if 2. is concluded and the lower limit of the two‐sided 95% confidence interval for the treatment difference (test‐active comparator) in PAR45 is greater than zero.; Secondary Objective: To assess Superiority of Nurofen forte® (the active comparator) over placebo in TOTPAR; (to demonstrate assay sensitivity), Global Assessment of Medication , Remedication time, Time to pain half gone, Time to any pain relief, Time to meaningful pain relief, Sum of Pain Intensity Difference (SPID), Safety ;
