E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
pain following extraction of impacted third molars |
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E.1.1.1 | Medical condition in easily understood language |
pain following extraction of impacted third molars |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Dentistry [E06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10044049 |
E.1.2 | Term | Dental pain and sensation disorders |
E.1.2 | System Organ Class | 100000004856 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective was to compare the safety and efficacy (onset, duration of relief, and overall efficacy) of a single dose of a fast release formulation of aspirin 1000 mg with the safety and efficacy of acetaminophen 1000 mg and placebo for relief of pain following extraction of impacted third molars. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective was to assess the efficacy and tolerability of the investigational products. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Healthy, ambulatory, male and female volunteers between 16 to 45 years of age - Scheduled to undergo surgical removal of either two partial bony impactions or one full bony alone or in combination with a partial bony impaction, soft tissue impaction or erupted third molar. Maxillary third molars may be removed regardless of impaction level - Use of only short-acting local anesthetic (e.g., mepivacaine or lidocaine) preoperatively, with or without vasoconstrictor and nitrous oxide - No use of any analgesics, nonsteroidal anti-inflammatory drug (NSAIDs), aspirin, any other pain reliever over the counter (OTC ) or prescription, or herbal supplements within 5 days of surgery. Oral contraceptives, prophylactic antibiotics, pre-anesthetic medication, anesthesia during the procedure, or other routine medications to treat benign conditions that would not confound the evaluation of the investigational would be acceptable - Female subjects of childbearing potential must be using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives), e.g., oral or patch contraceptives, intrauterine device, NuvaRing, Depo-Provera, or double-barrier and have a negative pregnancy test at Screening and prior to surgery. Female subjects of nonchildbearing potential must be amenorrheic for at least 2 years or had a hysterectomy and/or bilateral oophorectomy - Provide a personally signed and dated informed consent indicating that the subject has been informed of all pertinent aspects of the trial, (subjects < 18 years of age must sign a written assent and have parental or guardian consent) |
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E.4 | Principal exclusion criteria |
History of hypersensitivity to aspirin, salicylates, other nonsteroidal anti-inflammatory drug (NSAIDs), acetaminophen, opioid analgesics, and similar pharmacological agents or components of the investigational products, including the placebo - Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic diseases, or malignancies - Relevant concomitant disease such as asthma (exercise induced asthma is permitted), chronic sinusitis or nasal structural abnormalities causing greater than 50 percent obstruction (polyposis nasi, marked septal deviation) that can interfere with the conduct of the study in the judgment of the Investigator - Current or past history of bleeding disorder(s) - History of gastrointestinal bleeding or perforation, related to previous nonsteroidal anti-inflammatory drug (NSAID) therapy. Active, or history of recurrent peptic ulcer/hemorrhage (two or more distinct episodes of proven ulceration or bleeding) - Acute illness or local infection prior to surgery that can interfere with the conduct of the study in the judgment of the Investigator - Females who are pregnant or lactating - Positive alcohol breathalyzer test and/or positive urine drug or cotinine test prior to surgery |
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E.5 End points |
E.5.1 | Primary end point(s) |
•Time to meaningful pain relief |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•Time to first perceptible pain relief
•Time to first perceptible relief confirmed
•Pain Relief (PR) scores over each scheduled time points
•Sum of Pain Intensity Difference (PID) scores over each scheduled time points
•Time-weighted sum of Pain Intensity Relief (PID) scores
•Time-weighted Total Pain Relief (TOTPAR) scores
•Summed Pain Intensity Difference (SPID) 0-4 summary scores
•Summed Pain Intensity Difference (SPID) 0-6 summary scores
•Time to rescue medication
•The cumulative proportion taking rescue medication by time point
•Global assessment of pain relief at 6 hours post dose or immediately before the first intake of rescue medication |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Clinical trial sites will have the option of either contacting subjects within 2 to 5 (+/- 2 days) days after the last treatment period or scheduling subjects for an office appointment, depending on their standard of care policies, to assess the occurrence or persistence of adverse events, any medications taken, and for adequate treatment and follow up. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial months | 3 |