Efficacy and Safety Study of the Misoprostol Vaginal Priming Insert (MVPI) Prior to Hysteroscopy
Condition: Cervical Priming
Intervention: misoprostol; placebo
Intervention description: One vaginal insert containing 100, 200, 400, 800, 1200, 1600 mcg misoprostol administered intravaginally one time and remain in place for 18 - 24 hours prior to the hysteroscopy procedure. An adaptive design will be used to determine whether to escalate or reduce the dose, starting with MVPI 400 mcg.; placebo
Intervention MeSH terms: Misoprostol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 51.0
Sex: Female
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Hysteroscopy; Cervical priming; Cervical dilatation; Misoprostol; Endoscopy, uterine

Summary:

      A Phase II, multicenter, double-blind, randomized, placebo-controlled, dose-ranging, study to
      assess the efficacy and safety of the 100, 200, 400, 800, 1200 and 1600 mcg Misoprostol
      Vaginal Priming Insert (MVPI) for Women Requiring Cervical Priming prior to an in-office
      hysteroscopy procedure. Each subject will be randomized to receive one vaginal insert. The
      study drug will be administered vaginally by a member of the clinical research team (Part I)
      or insert herself (Part II) 18 - 24 hours prior to the scheduled hysteroscopy clinic visit.
      The internal os of the cervix will be measured at baseline, just prior to the hysteroscopy
      and at the follow up visit. The primary outcome measure is change in diameter of the internal
      cervical os from baseline (pre-treatment) to just prior to the hysteroscopy procedure
      (post-treatment). The hypothesis is that treatment with the MVPI will soften and dilate the
      cervix better than placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy, pre-menopausal women;

          -  Women aged 18 years and above;

          -  Women who are undergoing an in-office procedure requiring uterine access along with a
             cervical dilatation of at least 5.5 mm;

          -  Women participating in Part 1 of study: Women who have had at least one vaginal
             delivery of at least 24 weeks gestation;

          -  Women with Pap smear results that do not require further evaluation for at least one
             year as assessed by the investigator. Note: 1) results must be from a Pap smear
             obtained within one year of screening; 2) if results are unavailable or not current, a
             Pap smear must be obtained and results reviewed prior to study inclusion; 3) if a Pap
             smear is to be performed at screening, subject must have a negative pregnancy test
             confirmed prior to the Pap smear collection;

          -  Women of child bearing potential: 1) Must have a negative urine pregnancy test at
             screening and just prior to study drug insertion, if this takes place on a different
             day from the screening visit; 2) Agree to use a highly effective method of birth
             control (defined as a low failure rate of less than 1% per year) as follows: implants,
             injectables, combined oral contraceptives, sexual abstinence from the date of the
             subject's last menstruation until completion of the follow-up visit, vasectomised
             partner or barrier method (condom with spermicide). Women in a same sex relationship
             do not need to meet this criterion if they confirm that there is no possibility of
             pregnancy;

          -  Women who agree to refrain from vaginal intercourse while the study drug is in place;

          -  Women who agree to refrain from using any of the following from the day of study drug
             insertion until completion of the follow-up visit: feminine deodorant sprays/products,
             spermicides*, douches, condoms*, tampons, diaphragms or any other pharmaceutical or
             over the counter vaginal product. Barrier methods of contraception as indicated above
             (*) may be resumed following the dilatation procedure;

          -  Women who provide written informed consent.

        Exclusion Criteria:

          -  Menopausal women;

          -  Women with menstrual periods lasting >10 days in duration;

          -  Baseline internal cervical os ≥ 3 mm;

          -  Women who have had prior endometrial ablation;

          -  Women who are breastfeeding;

          -  History or current diagnosis of glaucoma;

          -  Women with clinically significant vaginal or cervical abnormality (e.g. symptoms of an
             infection) that would interfere with conducting study procedures prior to study drug
             insertion;

          -  Women who are currently undergoing treatment for cancer (basal cell carcinoma is
             acceptable);

          -  Body Mass Index (BMI) ≥ 50;

          -  Women participating in Part 1 of study: Women with a history of loop electrosurgical
             excision procedure (LEEP) or cold knife conization without an intervening vaginal
             delivery;

          -  Women with an intra-uterine device (IUD) in place, had an IUD removed within 30 days
             of the screening visit or scheduled to have an IUD inserted during the hysteroscopy
             procedure;

          -  Women using NuvaRing® for contraception;

          -  Known or suspected allergy to misoprostol, other prostaglandins or any of the
             excipients;

          -  Unable to comply with the protocol.