| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Mouth and tooth diseases [C07] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10054711 |
| E.1.2 | Term | Postoperative pain |
| E.1.2 | System Organ Class | 100000004863 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061812 |
| E.1.2 | Term | Dental operation |
| E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
| 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 |
| To compare a single oral dose of the fixed dose combination (FDC) relative to naproxen sodium 220mg, Caffeine 200 mg and placebo |
|
| E.2.2 | Secondary objectives of the trial |
1. To compare a single oral dose of the FDC relative to naproxen sodium 220mg, Caffeine 200 mg and placebo.
2. To compare the overall analgesic efficacy of two tablets vs. one tablet dosing for each level of caffeine dose (65 and100 mg) in the FDC product
3. To assess the safety and tolerability of the investigational product in terms of adverse events (AEs) and clinical parameters |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Healthy, ambulatory, male or female volunteers 16 years of age or older;
- Body mass index (BMI) 18.5 to 35.0 kg/m^2 inclusive as measured by the National Institutes of Health (NIH) BMI Calculator;
- Participants will undergo surgical extraction of three or four third molars, two of which must be mandibular molars. Maxillary third molars may be removed regardless of impaction level. The mandibular extractions must have a trauma rating of mild or moderate and meet one of the following scenarios: two full bony impactions; two partial bony impactions; one full bony impaction in combination with one partial bony impaction. supernumerary teeth present may also be removed at the discretion of the oral surgeon;
- Have not taken any form of medication, nutritional supplements with analgesic properties (e.g. gamma-Aminobutyric acid [GABA], turmeric) or herbal supplements (i.e., St. John’s Wort) within 5 days of admission (except for oral contraceptives, prophylactic antibiotics, multivitamin supplements, or other routine medications to treat benign conditions (such as antibiotics to treat acne), and agree not to take any medication (other than that provided to them) throughout the study;
- Use of only short-acting local anesthetic (e.g., mepivacaine or lidocaine) preoperatively, with or without a vasoconstrictor and nitrous oxide at the discretion of the Investigator;
- Have moderate to severe postoperative pain on the Categorical Pain Intensity Scale (a score of at least 2 on a 4 point scale) and a score of ≥ 5 on the 0-10 pain intensity Numerical Rating Scale (NRS) within 4.5 hours post-surgery. |
|
| E.4 | Principal exclusion criteria |
Inclusion Criteria:
- Healthy, ambulatory, male or female volunteers 16 years of age or older;
- Body mass index (BMI) 18.5 to 35.0 kg/m^2 inclusive as measured by the National Institutes of Health (NIH) BMI Calculator;
- Participants will undergo surgical extraction of three or four third molars, two of which must be mandibular molars. Maxillary third molars may be removed regardless of impaction level. The mandibular extractions must have a trauma rating of mild or moderate and meet one of the following scenarios: two full bony impactions; two partial bony impactions; one full bony impaction in combination with one partial bony impaction. supernumerary teeth present may also be removed at the discretion of the oral surgeon;
- Have not taken any form of medication, nutritional supplements with analgesic properties (e.g. gamma-Aminobutyric acid [GABA], turmeric) or herbal supplements (i.e., St. John’s Wort) within 5 days of admission (except for oral contraceptives, prophylactic antibiotics, multivitamin supplements, or other routine medications to treat benign conditions (such as antibiotics to treat acne), and agree not to take any medication (other than that provided to them) throughout the study;
- Use of only short-acting local anesthetic (e.g., mepivacaine or lidocaine) preoperatively, with or without a vasoconstrictor and nitrous oxide at the discretion of the Investigator;
- Have moderate to severe postoperative pain on the Categorical Pain Intensity Scale (a score of at least 2 on a 4 point scale) and a score of ≥ 5 on the 0-10 pain intensity Numerical Rating Scale (NRS) within 4.5 hours post-surgery.
Exclusion Criteria:
- History of hypersensitivity to naproxen sodium, caffeine, ibuprofen, nonsteroidal anti-inflammatory drug (NSAIDS), aspirin, similar pharmacological agents, local anesthetics, rescue medication or components of the investigational products;
- Evidence or history of clinically significant (in the judgment of the investigator) hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular (including hypertension and cardiac arrhythmia), hepatic, psychiatric, neurologic diseases, or malignancies within the last 5 years;
- Participants with the following medical conditions may be eligible at the discretion of the investigator: attention deficit hyperactivity disorder (ADHD) on a stable dose regimen of methylphenidate/(dextro) amphetamine for at least 6 months; participants with hypothyroidism on a stable dose of synthetic thyroid hormone for at least 6 months;
- Have received any form of treatment in the form of medication for depression in the past 6 months or any form of psychotropic agent (including selective serotonin uptake inhibitors [SSRI] but excluding ADHD medications described above) within the last 6 months;
- Relevant concomitant disease such as asthma (exercise induced asthma is permitted);
- Current or past history of gastrointestinal ulceration, gastrointestinal bleeding or other bleeding disorder(s);
- Acute illness or active local infection prior to surgery that can interfere with the conduct of the study in the judgment of the investigator;
- Use of any over-the-counter (OTC) or prescription medications with which the administration of naproxen, acetaminophen, ibuprofen, any other NSAID, (e.g., tramadol) or if a medication is contraindicated;
- Use of any medications within 5 days of surgery until discharge from the study site (except oral contraceptives, prophylactic antibiotics, synthetic thyroid hormones, methylphenidate or medications to treat benign conditions such as antibiotics to treat acne);
- Use of caffeine within 2 days prior to the study;
- Habits of high consumption of caffeine (>400 mg/day equivalent to about 3-4 cups of coffee per day);
- Habituation to analgesic drugs including opioids (i.e., routine use of oral analgesics 5 or more times per week for greater than 3 weeks within the past 2 years);
- Surgeon’s trauma rating of severe following surgery. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Sum of pain intensity difference (SPID) over 8 hours |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1. Sum of pain intensity differences from 0 to 2, 4 and 12 hours post-dose
2. Total pain relief from 0 to 2, 4, 8, and 12 hours post-dose
3. Time to first use of rescue medication
4. The cumulative proportion of participants taking rescue medication
5. Time to first perceptible relief, time to meaningful relief, and time to first perceptible relief confirmed by meaningful relief
6. Pain Intensity Difference (PID) and Pain Relief scores at each evaluation
7. Peak PID and peak pain relief score
8. Cumulative percent of participants with at least a 2-point PID
9. Global assessment of the investigational product
10. Number of participants with adverse events
11. Number of subjects with clinically significant changes in physical examinations, vital signs or laboratory assessments |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to 2, 4 and 12 hours, respectively
2. Up to 2, 4, 8 and 12 hours, respectively
3. Up 12 hours post dose
4. Up 12 hours post dose
5. Up 12 hours post dose
6. Up 12 hours post dose
7. Up 12 hours post dose
8. Up 12 hours post dose
9. Up 12 hours post dose
10. After the first dose of the investigational products in the treatment period
11. After the first dose of the investigational products in the treatment period |
|
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | No |
| 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 | 7 |
| 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 |
|
| 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
|
| End of follow up (phone call) |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
