Clinical trial NCT03448536: A Study to Assess Menstrual Cramp Pain Associated With Primary Dysmenorrhea
Official title: A Double-Blind, Randomized, Crossover Study to Assess Menstrual Cramp Pain Associated With Primary Dysmenorrhea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Dysmenorrhea
Keywords: Primary dysmenorrhea of at least moderate severity
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2018-02-28
Enrollment: 201
Sex: FEMALE
Minimum age (years): 15
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the maximum single dose of Aleve® (two tablets, equivalent to 440 mg of naproxen sodium) to the maximum single dose of Tylenol Extra Strength (two caplets, equivalent to 1000 mg of acetaminophen) in the treatment of menstrual pain associated with primary dysmenorrhea.


Eligibility criteria: Inclusion Criteria:

* Ambulatory healthy female patients between 15 and 35 years of age;
* Patient has a history of Over-the-Counter (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, 0-3) 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 an 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.

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 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.

Primary outcomes:
measure: Sum of Total Pain Relief (TOTPAR) Over 0-12 Hours
timeFrame: Up to 12 hours post-dose
Secondary outcomes:
measure: Summed Pain Intensity Difference (SPID) Over 0-12 Hours
timeFrame: Up to 12 hours post-dose
measure: SPID Over 0-6 Hours
timeFrame: Up to 6 hours post-dose
measure: SPID Over 6-12 Hours
timeFrame: From 6 hours to 12 hours post-dose
measure: TOTPAR Over 0-6 Hours
timeFrame: Up to 6 hours post-dose
measure: TOTPAR 6-12 Hours
timeFrame: From 6 hours to 12 hours post-dose
measure: Time to First Intake of Rescue Medication
timeFrame: Up to 12 hours post-dose
measure: Pain Intensity Difference (PID) Scores at Each Evaluation
timeFrame: Up to 12 hours post-dose
measure: Number of Participants by Global Evaluation Scores
timeFrame: Up to 12 hours post-dose
measure: Pain Relief Scores at Each Evaluation
timeFrame: Up to 12 hours post-dose
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Radiant Research, Inc.
state: Arizona
city: Scottsdale
country: United States
facility: Radiant Research, Inc.
state: Arizona
city: Pinellas Park
country: United States
facility: Radiant Research, Inc.
state: Florida
city: Chicago
country: United States
facility: Radiant Research, Inc.
state: Illinois
city: Akron
country: United States
facility: Radiant Research, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: Radiant Research, Inc.
state: Ohio
city: Dallas
country: United States
facility: Radiant Research, Inc.
state: Texas
city: Plano
country: United States
facility: Synexus US, LP- Plano
state: Texas
Study officials:
References:
citation: Daniels SE, Paredes-Diaz A, An R, Centofanti R, Tajaddini A. Significant, long-lasting pain relief in primary dysmenorrhea with low-dose naproxen sodium compared with acetaminophen: a double-blind, randomized, single-dose, crossover study. Curr Med Res Opin. 2019 Dec;35(12):2139-2147. doi: 10.1080/03007995.2019.1654987. Epub 2019 Aug 28.