E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10062851 |
E.1.2 | Term | Primary dysmenorrhea |
E.1.2 | System Organ Class | 100000004872 |
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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 of this study is to evaluate the analgesic efficacy of a maximum single dose of two tablets of Aleve (2 x naproxen sodium 220 mg; total dose 440 mg) as compared to two tablets of Tylenol Extra Strength (2 x acetaminophen 500 mg; total dose 1000 mg) for the treatment of menstrual cramping pain associated with primary dysmenorrhea. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of naproxen sodium and acetaminophen. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Ambulatory healthy female patients between 15 and 35 years of age; - Patient has a history of OTC analgesic use for treatment of primary dysmenorrhea; - Patient has a history of regular menstrual cycles that typically occurs between every 21 to 35 days; - Patient has a self-reported history of primary dysmenorrhea (onset <5 years after menarche) with at least moderate menstrual cramp pain (based on the categorical pain intensity scale) occurring during four of the past six menstrual cycles; - Patient has a self-reported history of primary dysmenorrhea with other causes of dysmenorrhea having been excluded; - Patient typically requires at least one dose of a OTC analgesic medication such as naproxen, aspirin, acetaminophen, or ibuprofen taken on at least 1 day of her menstrual cycle for the treatment of moderate or severe menstrual cramp, and normally experiences pain relief from these medications; - Patient is of child-bearing potential and is using one of the following methods of contraception and agrees to continue this same method for the duration of the study: -- Abstinence for at least the last 60 days AND willingness to use double barrier method should the patient become sexually active during the study; -- Double barrier method (condom with contraceptive foam, diaphragm with contraceptive gel); -- Permanent sterilization of patient or her spouse/partner; -- Oral contraceptive (must have been using the same oral contraceptive for at least three months prior to study entry and agrees to remain on the same type and method throughout the course of the study). - Patient is willing to participate in the study and return to the study site within approximately 1 week after her menstrual cycle to return the study medication, urine pregnancy test, and for review of the completed patient e-diary; - Patient is willing to abstain from alcohol consumption throughout the 12-hour Treatment Period; - Patient is willing to abstain from caffeine consumption throughout the 12-hour Treatment Period; - Patient is willing to ingest the overencapsulated tablets throughout the study; - Patient is willing and able to participate in all scheduled visits, treatment plan, laboratory tests and other study procedures according to the clinical protocol. |
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E.4 | Principal exclusion criteria |
- Patient has a known history of allergic, idiosyncratic or serious adverse reaction, to acetaminophen, naproxen, aspirin, ibuprofen, or any other nonsteroidal anti-inflammatory drug (NSAID); - Patient has a known allergy to any of the excipients in any of the study medication products; - Patient has experienced asthma, urticaria, or allergic-type reactions after taking aspirin, acetaminophen or other NSAIDs; - Patient has significant co-existing illness, including gastrointestinal, hepatic, renal, neurologic, cardiovascular, psychiatric, endocrine, respiratory, surgical procedure or other condition that, in the Investigator’s judgment, contraindicates administration of the study medication; - Patient has a current or past history of severe gastritis, gastrointestinal bleeding or ulceration; - Patient has a current or past history of one or more of the following conditions: secondary dysmenorrhea, pelvic inflammatory disease, urinary tract infection (currently acute or recurrent [defined as more than three per year]), prior history of an urinary tract infection is eligible for enrollment, adnexal masses, uterine fibroids, endometriosis, adenomyosis that in the opinion of the Investigator would impact patient safety and/or the study data; - Patient has an ongoing sexually transmitted disease (except for a history of genital herpes or Human Papillomavirus) or has abnormal vaginal discharge; - Patient requires prescription analgesics, narcotic, non-NSAID (i.e., defined as oral use of 5 or more times per week for greater than 3 weeks) or has routinely taken OTC medications in excess of label recommended instructions for control of dysmenorrhea symptoms; - Patient is taking mood-altering agents (e.g., antidepressants, sedatives, phenothiazines, or anti-anxiety agents). Patients who are on a stable dose for at least 3 months, and not taking this medication for dysmenorrhea or premenstrual syndrome are eligible for enrollment; - Patient does not agree to abstain from taking any analgesic and/or anti-inflammatory medication (with the exception of low dose aspirin [defined as no greater than 100 mg daily] taken for cardioprotective purposes) approximately 72 hours prior to the anticipated treatment period and throughout the dosing/assessment period. All pain and anti-inflammatory medications including supplements, topical heat or cold, and other products of topical application will be discontinued approximately 72 hours prior to the anticipated dosing for each treatment period and throughout the dosing/assessment period; - Patient does not agree to abstain from using transcutaneous electrical nerve stimulation devices that are used to treat dysmenorrhea throughout each treatment period; - Patient is taking piroxicam (Feldene®) or oral corticosteroids. Patients taking inhaled or topical corticosteroids are eligible for enrollment; - Patient is pregnant, lactating , or less than 6 months postpartum; - Patient is currently using an intra-uterine devices (IUD), or using hormonal implants (e.g., Norplant) or injections (e.g., Depo-Provera) for contraception or used within the past 6 months; - Patient is currently using an oral contraceptive for less than 3 months, has been on a unstable dose within the last 3 months or has switched from one oral contraceptive to another within the last 3 months or intends to do so in the course of the study; - Patient has a history of chronic abuse of alcohol (regularly consumes 3 or more alcoholic drinks per day), analgesics, narcotic analgesics, ergot alkaloids, tranquilizers, or opioids or other substances known to produce dependence; in the judgement of the investigator within the past 3 years; - Positive drug screen at screening and visit 2 for illegal drug substances, or non-prescribed controlled substances; - Positive pregnancy test or breast feeding at screening and prior to dosing in each Treatment Period; - Patients with a medical disorder, condition or history such that could impair the patient’s ability to participate or complete this study in the opinion of the investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Sum of Total Pain Relief (TOTPAR) over 0-12 hours (TOTPAR0-12) |
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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) |
• Summed Pain Intensity Difference (SPID) over the 12-hour study period .(SPID0-12) using 0-10 NRS; • SPID over 0-6 hours (SPID0-6); • SPID 6-12 hours (SPID6-12); • TOTPAR over 0-6 hours (TOTPAR0-6); • TOTPAR 6-12 hours (TOTPAR6-12); • Time to first intake of rescue medication; • Pain Intensity Difference (PID) scores at each evaluation; • Global Evaluation at 12 hours post-dose or immediately before first intake of rescue medication; • The number of subjects with adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• 12 hours post-dose; • 6 hours post-dose ; • From 6 hours to 12 hours post-dose; • 6 hours post-dose; • From 6 hours to 12 hours post-dose; • Up to 12 hours post-dose; • 12 hours post-dose; • Up to 12 hours post-dose; • Up to 5 months |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial months | 6 |