Effects of Simvastatin on Uterine Leiomyoma Size

Inclusion Criteria:

• Signed informed written consent.

• Gender: female.

• Age: 18-55 years at time of signing consent.

• BMI of subjects: < 45 kg/m2.

• Uterine fibroids:

• Diagnosed by ultrasound (MRI will be used only if ultrasound is inconclusive).

• Number: any number of fibroids.

• Location: submucosal or intramural.

• At least one fibroid of diameter > 3cm.

• Symptoms: one or more of the following symptoms of heavy menstrual bleeding (HMB),defined as: Experienced cyclic (22 to 35 days) abnormal uterine bleeding (heavy orprolonged) in at least 3 of the last 6 menstrual periods, including menstrualbleeding lasting 5 or more days or heavy bleeding per participant recall. Examplesof heavy bleeding may include, but are not limited to the following:

• Requires the use of double protection to manage menstrual bleeding.

• Menstrual bleeding accompanied by the sensation of "gushing" or "flooding".

• Saturates more than 1 tampon or sanitary pad per hour for 3 or more consecutivehours.

• Regularly needs to change the tampon or sanitary pad at night or regularly soilsbedclothes.

• Heavy bleeding that affects work, school, or social activities.

• Pelvic pain/ pressure likely caused by fibroids.

• Plan for surgery (hysterectomy or myomectomy).

• Normal Pap smear within the last year.

• Use of contraception during study such as non-hormonal oral contraceptives,intrauterine devices (IUD)/ intrauterine systems (IUS), barrier contraceptives,abstinence or sterilization.

Exclusion Criteria:

• Pregnancy or lactation.

• Previous or current uterine, cervical or ovarian cancer.

• Current endometrial hyperplasia or history of atypical endometrial hyperplasia.Endometrial biopsy will be done during screening (if not done within last 12months).

• Suspicion of leiomyosarcoma.

• Recent rapid growth of fibroids (i.e. doubling in size within 1-6 months period).

• Unevaluated gynecologic abnormalities (unexplained vaginal bleeding, cervicaldysplasia, or abnormal adnexal/ovarian mass).

• Menopausal status.

• Surgery is urgently indicated (< 3 months) for medical or social reasons.

• Hemoglobin ≤ 6 g/dL.

• Currently enrolled in another investigational study.

• Mental condition or other barrier preventing informed written consent.

• Allergy or hypersensitivity to simvastatin.

• Current use of simvastatin or other drugs of the same class.

• Concomitant administration of strong CYP3A4 inhibitors including itraconazole,ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin,telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, andcobicistat-containing products.

• Concomitant administration of gemfibrozil, cyclosporine, or danazol, verapamil,diltiazem, amiodarone, diltiazem, dronedarone, amlodipine, ranolazine, lomitapide,and grapefruit juice.

• Active liver disease, which may include unexplained persistent elevations in hepatictransaminase levels.( elevation of aspartate transaminase and/or alaninetransaminase > 2 s.d. above the normal range at screening visit)

• Known increased risk or diagnosis of a myopathy.