Dysmenorrhea
Conditions
Keywords
Dysmenorrhea, Periods, Menstrual, Primary dysmenorrhea in women with recurrent dysmenorrhea
Brief summary
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).
Detailed description
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.
Interventions
DRUGLidocaine
Lidocaine vaginal gel 10% (150mg) administered once daily for 4 days
DRUGPlacebo
Placebo vaginal gel administered once daily for 4 days
Sponsors
Juniper Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Primary Efficacy Variable Will be the Time-weighted Average Pain Intensity Over 4 Treatment Days Using the 4 Point Categorical Scale. | Two 4-day dosing regimens for two consecutive monthy menstrual cycles |
| Treatment-emgergent Adverse Events | approximately two months, based on onset of menses |
Secondary
| Measure | Time frame |
|---|---|
| Evaluate Electrocardiograms (ECGs) for Potentially Significant QT Changes at Approximate Peak Lidocaine Plasma Concentration After 4 Days of Dosing | 7 hours following fourth dose in 2 consecutive menstrual cycles |
Countries
United States
Participant flow
Recruitment details
Clinics and private practice offices; 8/31/07-6/13/08. Maximum patient participation was approx 4 months, including 45 day screening period, a treatment period of approx 8 weeks duration (during which subjects received study drug on a total of 8 days), and a post treatment visit occurring 2 - 3 weeks after Treatment Cycle 2,Visit 5.
Pre-assignment details
Crossover study; Subjects who met study entry criteria after completing screening procedures at Screening Visit returned to study center at least 7 days prior to their expected onset of menses to complete Randomization/Treatment procedures. Abnormal lab values, ECGs or use of prohibited medications were among reasons subjects were excluded.
Participants by arm
| Arm | Count |
|---|---|
| Active Lidocaine 10% (150mg) vaginal gel | 41 |
| Placebo Placebo vaginal gel | 43 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adminstrative Discontinuation | 2 | 3 |
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Placebo | Active | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 43 Participants | 41 Participants | 84 Participants |
| Age Continuous | 27.7 years STANDARD_DEVIATION 6.69 | 26.5 years STANDARD_DEVIATION 7.2 | 27.1 years STANDARD_DEVIATION 6.92 |
| Region of Enrollment United States | 43 participants | 41 participants | 84 participants |
| Sex: Female, Male Female | 43 Participants | 41 Participants | 84 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 77 | 7 / 77 |
| serious Total, serious adverse events | 0 / 77 | 0 / 77 |
Outcome results
Primary
The Primary Efficacy Variable Will be the Time-weighted Average Pain Intensity Over 4 Treatment Days Using the 4 Point Categorical Scale.
Time frame: Two 4-day dosing regimens for two consecutive monthy menstrual cycles
Population: Time-weighted average pain intensity over the 4 treatment days using the 4 point categorical scale - none (0), mild (1), moderate (2), and severe (3); primary efficacy variable. ITT Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lidocaine 10% | The Primary Efficacy Variable Will be the Time-weighted Average Pain Intensity Over 4 Treatment Days Using the 4 Point Categorical Scale. | 0.91 units on a scale | Standard Deviation 0.635 |
| Placebo Gel | The Primary Efficacy Variable Will be the Time-weighted Average Pain Intensity Over 4 Treatment Days Using the 4 Point Categorical Scale. | 0.92 units on a scale | Standard Deviation 0.552 |
Primary
Treatment-emgergent Adverse Events
Time frame: approximately two months, based on onset of menses
Secondary
Evaluate Electrocardiograms (ECGs) for Potentially Significant QT Changes at Approximate Peak Lidocaine Plasma Concentration After 4 Days of Dosing
Time frame: 7 hours following fourth dose in 2 consecutive menstrual cycles