IncobotulinumtoxinA for Provoked Vestibulodynia With Overactive Pelvic Floor Muscle Dysfunction

A Double Blind, Placebo Controlled Study of IncobotulinumtoxinA in Patients With Provoked Vestibulodynia Associated With Overactive Pelvic Floor Muscle Dysfunction

This is a double-blind, placebo-controlled study evaluating the safety and efficacy of incobotulinumtoxinA (Merz) for the treatment of provoked vestibulodynia (PVD) associated with overactive pelvic floor muscle dysfunction. Eligible participants are premenopausal females aged 18 years and older with a confirmed diagnosis of PVD with hypertonic pelvic floor muscles, established by both an expert physician and an expert pelvic floor physical therapist. Participants must have bilateral provoked pain at the posterior vestibule on cotton swab testing and a pain score of 5 or greater on an 11-point Numeric Rating Scale (NRS) during standardized dilator testing at baseline. Key outcome measures include change in pain during dilator testing and Patient Global Impression of Change (PGI-C). Participants with anterior vestibular pain, prior botulinum toxin injection in the genitopelvic area within the past 12 months, or significant genitourinary conditions that may confound assessment are excluded.

Inclusion Criteria:

• Female, 18 years or older.

  • Willing to provide a written informed consent prior to any study related procedures.
  • Premenopausal.
  • Have vulvodynia with provoked vestibulodynia with overactive pelvic floor muscle dysfunction for at least 3 months duration and for no more than 15 years.
  • Have provoked pain at the posterior vestibule on a cotton swab test, with pain at positions 4, 6 and 8 o'clock (must be bilateral pain) at the Baseline Visit.
  • Have independently confirmed diagnoses of provoked vestibulodynia PVD with overactive pelvic floor muscle dysfunction (hypertonic pelvic floor muscles) confirmed by both an expert physician and expert pelvic floor physical therapist.
  • Are able to tolerate the smallest dilator size (diameter 0.5 inches) at the Baseline Visit, i.e. agree to the next successive dilator size to be tested for pain response (i.e. the two smallest sized dilators (#1 and 2) are to be tested).
  • Pain score ≥5 on an 11-point Numeric Rating Scale (NRS) for the Dilator Maximum Tested Size (DMTS) at the Baseline Visit.
  • Willing and able to comply with study restrictions, able to attend the clinic for the required duration of assessments during the study period and willing to return to the clinic for the follow-up evaluation as specified in the protocol.
  • If the subject has received oral antidepressants, anxiolytics or anti-epileptics, then the dose of these medications should have been stable for at least 3 months prior to the Baseline Visit and expected to remain stable throughout the study.
  • If the subject is currently undergoing pelvic floor physical therapy then the frequency of visits should be stable for at least 8 weeks prior to the Baseline visit and expected to remain stable throughout the study.
  • If the subject has vaginal/vulvar infections (bacterial vaginosis, presence of candidiasis or trichomoniasis) at Baseline Visit (provider will take a vaginal culture swab to test for infection), they may still participate as long as they undergo treatment for the infection (as prescribed by study provider).

Exclusion Criteria:

• Have provoked pain on a cotton swab test at the anterior vestibule (anywhere between 9 and 3 o'clock or more anteriorly) at the Baseline Visit.

  • Able to tolerate the 6th (diameter 1 1⁄4 inches) dilator size (i.e. agree to the next successive dilator size to be tested for pain response) at the Baseline Visit with a pain score less than 5 (i.e. blue dilator).
  • Genitourinary or gastrointestinal conditions/history which, according to the investigator's judgment may interfere with treatment or impact outcome assessment, including but not limited to:
  • Skin disease at the vestibule such as lichen sclerosus, lichen planus, vaginal or vulvar atrophy, desquamative inflammatory vaginitis, allergic vulvitis, etc.
  • Severe endometriosis (as defined as requiring regular medications other than hormonal contraceptives and NSAIDS to manage the endometriosis symptoms).
  • Pudendal neuralgia (as defined as greater than minimal tenderness to palpation of the pudendal nerves at the ischial spine).
  • Genitourinary or rectal cancer.
  • Congenital urogenital abnormalities (e.g. vaginal septa, imperforate hymen, urethral diverticulum).
  • Pain in urethra (diagnosis based on subject's interview and physical examination).
  • Symptomatic urogenital prolapse at physical examination.
  • History of traumatic or post radiotherapy vulvar lesions.
  • Previous surgery that according to the investigator's judgment may impact on study outcome including but not limited to vaginal hysterectomy, vestibulectomy, urolxogic surgery (slings, colporrhaphy, etc.), perianal surgery or genital trauma or mutilation/cutting.
  • Current vaginal/vulvar infections (bacterial vaginosis, candidiasis, or trichomoniasis) and are unwilling or unable to take oral medication to treat this infection.
  • Clinically significant history of alcohol/drug abuse the last 24 weeks prior to Baseline or clinically significant alcohol/drug dependence within 2 years prior to Baseline. Exceptions include caffeine or nicotine abuse/dependence.
  • Has received any of the following:
  • Pelvic floor physical therapy initiated, stopped or modified (frequency or type of physical therapy) during the last 8 weeks prior to Baseline (physical therapy includes but is not limited to: internal/external myofascial release by physical therapist, biofeedback, home pelvic floor exercises, self-taught exercises, use of vaginal dilators, etc.).
  • Treatment with any muscle relaxants in the past 2 weeks.
  • Treatment for anterior vestibular pain, with hormonal creams, in the last 1 week prior to Baseline unless continued at the same dosing regimen throughout the study.
  • Currently receiving treatment for stress or urge urinary incontinence.
  • Injections of steroids in the vulva within the last 4 weeks prior to the Baseline Visit or planned use during the study.
  • Injection of BoNT in the genitopelvic area within the last 12 months prior to the Baseline visit.
  • Treatment with an investigational drug within the last 4 weeks prior to Baseline or scheduled treatment with such a drug during the study period.
  • Is likely to require treatment during the study with drugs that are not permitted by the study protocol.
  • Any mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude, as judged by the investigator.
  • Women who are pregnant or planning to become pregnant during the study, or who are currently lactating (breastfeeding). Participants should either not have sexual intercourse with a male partner or should use a method of birth control that is acceptable to them and the study doctor during the time that they participate in the protocol. Acceptable forms of contraceptives include: progestin and/or estrogen-containing hormonal contraceptives, contraceptive patch, contraceptive implant, contraceptive injection, condoms, or progestin or copper-containing intrauterine device (IUD), tubal sterilization, vasectomy of all sexual partners.