Clinical Study to Compare Efficacy and Safety of Indinol Forto® 200 mg Capsules and Visanne 2 mg Tablets in Treatment of Endometriosis

Inclusion criteria

• The participant provides written informed consent for participation in the study in accordance with current legislation.
• Female participants in reproductive/premenopausal period from 18 to 45 years old inclusively (at the moment of signing informed consent).
• Participants have been surgically (laparoscopy or laparotomy) diagnosed with endometriosis (ICD code #80) within not more than 60 months and not less than 2 weeks of study entry, stage I-III according to endometriosis revised classification of American Fertility Society (R-AFS, 1985)).
• Participant has had spontaneous, (i.e., without hormonal therapy) regular, menstrual cycles with a cycle length between 24 to 38 days (inclusive) for the past 2 cycles before Visit 0 and during screening period.
• Participant has no current indications for surgical treatment of endometriosis.
• Participant has had endometriosis-related pelvic pain assessed with visual analogue scale (VAS) and defined as average daily pain score ≥3.5 cm during 2 menstrual cycles prior to screening (assessed by the participant retrospectively at the moment of screening) and during screening menstrual cycle (according to the data from the participant's diary completed daily).
• Presence of other symptoms of endometriosis (e.g. dysmenorrhea, dyspareunia, dyschezia, data of ultrasound imaging, or magnetic resonance imaging (MRI).
• The participant agrees to use highly effective contraception methods described in the protocol from the time of signing informed consent through the whole duration of the study and for 2 months after the study completion.
• Negative pregnancy test.
• Participant completed daily diary on minimum 75% of days during screening menstrual cycle.

Exclusion criteria

• Presence of contraindications to Indinol Forto (indolcarbinol)
• Presence of contraindications to Visanne (dienogest)
• Participant had undiagnosed (unexplained), abnormal, vaginal or urinary tract bleeding within the past 6 months before screening (Visit 0).
• Participant has chronic pelvic pain not caused by endometriosis, but other gynecological or urological disorders (consequences of inflammatory process, uterine fibroids, pelvic congestion syndrome, etc.).
• Participant has chronic, non-pelvic pain not caused by endometriosis that requires chronic analgesic or other chronic therapy (including, but not limited to, fibromyalgia, chronic back pain or chronic headaches).
• Endometrioid cysts ≥ 3 cm.
• Participant has a surgical history of hysterectomy and/or bilateral oophorectomy; premature ovarian failure. Note: Participants who have undergone surgical sterilization (eg, bilateral salpingectomy, tubal ligation) are permitted in the trial.
• Participant has a clinically significant gynecologic condition identified in the screening evaluation including, but not limited to, ovarian cysts larger than 3 cm and present longer than 4 months, an active sexually transmitted disease, etc. Note: Participants may be rescreened after completing treatment for infection or for simple ovarian cysts.
• Participant with endometriosis-related pelvic pain who didn't respond to previous treatment with combined oral contraceptives, GnRH agonists or antagonist, progestins or aromatase inhibitors. Note: Participants who demonstrated partial response or interrupted their treatment due to side effects, may be enrolled in the study.
• History of malignancy, including suspected malignization of endometriomas within ≤5 years before signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
• Severe renal failure (glomerular filtration rate calculated with Cockcroft-Gault formula is below 30 ml/min/1,73 m2).
• Systolic blood pressure \>160 mm Hg or diastolic blood pressure \>90 mm Hg during screening period.
• Clinically significantly abnormal laboratory tests at Screening, including: alkaline phosphatase (AP), alanine aminotransferase (ALT, SGPT), aspartate aminotransferase (AST, SGOT) \>200% of the upper limit of normal, or total bilirubin \>150% of the upper limit of normal; hemoglobin \<10 g/dl, white blood cell count \<2500 in mm³, neutrophil count \<1500 in mm³, platelet count \<100 х 10³/mm³.
• Hyperthyroidism (TSH below 0.4 mU/L) or hypothyroidism (TSH above 4.0 mU/L).
• Positive pregnancy test (including pregnancy within 3 months prior to screening) or lactation period.
• Other medical conditions that, in the judgment of the Investigator, may increase the risk associated with study participation or may interfere with the interpretation of study results.
• History of alcohol or substance abuse.
• Participation in a clinical study within 90 days before screening.
• Other reasons that, in the judgment of the Investigator, may interfere with participation in the study or may lead to unreasonable risks.
• Conditions requiring surgery in the period of the study.
• Conditions requiring therapy prohibited by the study protocol.