Efficacy and Safety Study of Lidocaine Vaginal Gel for Recurrent Dysmenorrhea (Painful Periods)

A Phase II, Double-Blind, Crossover Study to Assess the Efficacy and Safety of 10% (150mg) Lidocaine Vaginal Gel Administered to Women With Recurrent Dysmenorrhea

The purpose of this study is to determine whether lidocaine vaginal gel is safe and effective for preventing or reducing the severity of dysmenorrhea (painful menstrual periods) compared to placebo (inactive gel).

The primary objective of this study is to evaluate the efficacy of 10% (150 mg) lidocaine gel compared with placebo in reducing the severity and onset of primary dysmenorrhea in women with recurrent dysmenorrhea.

The secondary objectives of this study are the following:

• to assess the safety of 10% (150 mg) lidocaine gel compared with placebo
• to evaluate electrocardiograms (ECGs) for potentially significant QT changes at approximate peak lidocaine plasma concentration after 4 days of dosing with 10% (150 mg) lidocaine gel.

Inclusion Criteria:

1. Experiences primary dysmenorrhea requiring pain medication for moderate-to-severe pain (as measured by a 4-point categorical rating scale) by the subject's own report for at least four of the previous six menstrual cycles.
2. Has a history of primary dysmenorrhea with onset within 4 years of menarche.
3. Has regular menstrual cycles (i.e. onset of menses predictable within 1 - 2 days each month) for the 3 month period preceding enrollment. If a subject has had regular cycles for the past 12 months but had a single cycle that was not regular within the 3 month period preceding enrollment, the subject may be enrolled at investigator discretion after consultation with sponsor.
4. Taking the same strength and type of hormonal contraception on a monthly cycle for at least the previous 6 months prior to screening and plans to remain on this hormonal contraception for the duration of participation in the study or is on an acceptable method of birth control including surgical sterilization (i.e. bilateral tubal ligation, partner vasectomy), double-barrier methods, and total abstinence (at the discretion of the investigator in cases where age, career, lifestyle, or sexual orientation of the patient ensures compliance).
5. Is a tampon user and/or must be willing to use tampons throughout the study dosing period.
6. Age 18 to 40 years (inclusive).
7. Has a Body Mass Index (BMI) ≤ 35 kg/m2.
8. Able to understand and willing to complete the efficacy evaluations.
9. Able to speak and understand English, and must give written informed consent for the study.

Exclusion Criteria:

1. Unable, in the opinion of the Investigator, to comply fully with any of the study requirements.
2. Experiencing pelvic pain other than that thought to be associated with primary dysmenorrhea, such as chronic pelvic pain occurring at times other than exclusively during menses and/or dyspareunia.
3. Experiencing dysmenorrhea symptoms that are effects of or thought to be effects of (at least in part) secondary causes of dysmenorrhea, such as uterine fibroids, endometriosis, and/or currently symptomatic ovarian cysts.
4. Experienced dysmenorrhea that did not require, in the opinion of the subject, the use of analgesic medication during four of the previous six menstrual episodes.
5. Has dysmenorrhea refractory to treatment with commonly used analgesic medications for the treatment of menstrual pain (e.g., ibuprofen or naproxen sodium).
6. Use of any Class I antiarrhythmic drug.
7. Currently using contraceptive injection, implant, or extended cycle OC (hormonal contraceptive cycles consisting of 28 days or more of active hormones).
8. Pregnant or breastfeeding.
9. Participated in a clinical trial in the 30 days from the time of last dosing in the prior study to the time of providing consent for this study.
10. Previously randomized into this study.
11. A history of allergic hypersensitivity or significant intolerance (including angioedema, urticaria, bronchospasm, and rhinitis) related to treatment with any medications used in this study.
12. A history of past or ongoing clinically significant disease, illness, or disorder that, in the opinion of the Investigator, makes the subject unsuitable for study participation including active vaginal, vulvar, and cervical lesions.
13. Laboratory abnormalities that, in the opinion of the Investigator, could contraindicate study participation such as liver function tests > 1.5 times the upper limit of normal (At the Investigator's discretion, laboratory tests may be repeated once for verification.)
14. A history of, within the past 4 years, or ongoing significant psychiatric illness that, in the opinion of the Investigator, makes the subject unsuitable for study participation.
15. A history of chronic analgesic or tranquilizer use or drug abuse including alcohol within the 6 months before providing consent for this study.
16. Regular use of any concomitant medications that might confound efficacy and/or safety assessments, in the opinion of the Investigator, including, but not limited to, the following: psychotropic drugs, antidepressants, sedative-hypnotics, sedating antihistamines, or tranquilizers for 24 hours or five half-lives prior to providing informed consent until 24 hours after the final treatment cycle. Selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and St. John's Wort are permitted for indications other than pain if the subject has been on a stable dose for at least 2 weeks before providing consent for this study and agrees to remain on a stable dose throughout the course of the study.
17. Unwilling to use only those medications that are allowed in the study for the treatment of their dysmenorrhea, i.e., study drug and rescue medication.
18. Any ongoing vaginal infection requiring intravaginal treatment.
19. A history of toxic shock syndrome (TSS).