SODIUM VALPROATE for Adenomyosis

Inclusion criteria

• {"criterion_text":"- [1]\tPremenopausal female, between 18 and 45 years of age inclusive, at the time of signing consent\n- [10]\tPatients who agree to use only ibuprofen 400 mg as rescue medication up to a total daily dose of not more than 2400 mg\n- [11]\tPatients willing and able (e.g. mental and physical condition) to participate in all aspects of the study as evidenced by providing signed written informed consent according to chapter 5.3 of clinical trial protocol\n- [12]\tPatient agrees to sexual abstinence during the entire duration of the screening, treatment and for the wash-out period of the study. Does not apply if the patient can confirm either of the following: • surgical sterilization or bilateral tubal occlusion.\n- [2]\tPatients with Adenomyosis - Associated Pelvic Pain (AAPP: i.e., any type of pelvic pain associated with adenomyosis: non-menstrual pelvic pain, dysmenorrhea and/or dyspareunia) as measured by Visual Analogue Scale (VAS) ≥ 40 units (as defined in chapter 9.3.1) at least once during screening period\n- [3]\tPatients with a history of AAPP for at least the past 6 months prior to the initial screening period\n- [4]\tAdenomyosis diagnosed by MRI or transvaginal ultrasound, or by means of hysteroscopy in the past 5 years\n- [5]\tPatients with one or more distinctive adenomyotic lesions, confirmed by transvaginal ultrasonography (TVUS) at screening\n- [6]\tPresence of one or more lesions suitable for treatment with Convulex, with the total dose not exceeding 40 mg (equivalent to 8 mL of the final solution at 5 mg/mL concentration), as identified under ultrasound guidance\n- [7]\tPatients with history of infertility and/or more than one spontaneous abortion\n- [8]\tPatients seeking to achieve pregnancy either through in-vitro fertilization (IVF) (optional) or spontaneous conception after the end of treatment with study medication and the wash-out period\n- [9]\tPatients with a history of regular menstrual cycles (21-35 days) while not being on any pharmacological treatment that could alter the menstrual cycle (e.g. oral contraceptive pills)"}

Exclusion criteria

• {"criterion_text":"- [1]\tHistory of hypersensitivity or intolerance to the active substance or any of the excipients of the study and rescue medication\n- [10]\tVisible myomas > 3 cm on ultrasound/MRI\n- [11]\tCervical smear with pathological findings: class III or higher according to Papanicolaou, class IIp or higher according to the Munich III nomenclature or ASC-US or higher according to the Bethesda system\n- [12]\tSurgical treatment of adenomyosis within 3 months prior to the screening period\n- [13]\tPresence of chronic pelvic pain other than pain due to adenomyosis\n- [14]\tAcute or chronic hepatitis\n- [15]\tHepatic insufficiency\n- [16]\tFamily history of severe hepatitis, especially drug related\n- [17]\tKnown hepatic porphyria\n- [18]\tAbnormal clinical and/or laboratory findings considered by the investigator as clinically relevant\n- [19]\tPositive results for HBs-Ag, anti-HCV and HIV-1/HIV-2-antibodies\n- [2]\tPresence of an intrauterine device (IUD); participants with IUDs must have them removed prior to enrollment\n- [20]\tThe use of antipsychotics or analgesics other than ibuprofen—including opioids, NSAIDs, paracetamol, or metamizole—is prohibited during the screening period. Short-term use (up to 3 days) of NSAIDs (other than ibuprofen) or metamizole is allowed for acute conditions (e.g., flu-like symptoms, emergency dental procedures or other acute conditions). The use of Fentanyl, Propofol, and Metoclopramide is also permitted only as short-term venous anaesthesia for the intralesional application of the study drug\n- [21]\tHistory of illicit drug or alcohol abuse within 6 months prior to screening visit\n- [22]\tParticipation in another trial within 3 months before the screening period\n- [23]\tPrevious enrolment in this study\n- [24]\tAny condition that, in the judgment of the investigator, may interfere with adherence to study procedures or study assessments\n- [25]\tUnreliability or lack of cooperation during the screening period\n- [26]\tUnwillingness or inability to complete the (paper) DIARY properly during the screening period\n- [27]\tRelatives and dependents of the PI/Sponsor; study site employees directly subordinate to the PI or sub-investigators\n- [28]\tLegal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequences of the study\n- [29]\tPatients who are known or suspected to be in custody or submitted to an institution due to a judicial order.\n- [3]\tPositive suicidal ideation at screening or Day 0\n- [4]\tKnown contraindications to the use of valproic acid (VPA), as specified in the SmPC, including epilepsy, systemic lupus erythematosus (SLE), hereditary enzyme deficiencies affecting the urea cycle, impaired kidney function, uncorrected systemic primary carnitine deficiency, or mitochondrial disorders caused by mutations in the nuclear gene encoding the mitochondrial enzyme polymerase γ (POLG), such as Alpers-Huttenlocher Syndrome\n- [5]\tSubject is pregnant or breast-feeding or is planning a pregnancy within the duration of the screening, treatment, and wash-out periods of the study or is less than 6 months postpartum or post-lactation or less than 1-month post-abortion, at the time of entry into the screening period\n- [6]\tPrevious or concomitant use of hormonal agents before the screening period: ≤ 24 weeks for GnRH agonists and hormonal implants (or longer, depending on the specific implant type); ≤ 12 weeks for depot progestogens and danazol; ≤ 6 weeks for oral and vaginal contraceptives\n- [7]\tPatients with history of any type of cancer (including breast cancer)\n- [8]\tOther clinically significant gynaecological condition already known or identified during the screening period such as symptomatic uterine fibroids requiring treatment\n- [9]\tPresence of ovarian cyst of unknown etiology"}

Primary endpoints

• {"endpoint_text":"- Pre−post absolute change between baseline and final value after 29 days treatment in AAPP","definition_or_measurement_approach":"Change measured from baseline to final value after 29 days; AAPP (adenomyosis-associated pelvic pain) assessed using Visual Analogue Scale (VAS) as described in main objective and chapter 9.3.1, considering intake of rescue medication."}
• {"endpoint_text":"- Final value at the end of 29 days of treatment in the amount of analgesic rescue medication taken (ibuprofen 400 mg tablets)","definition_or_measurement_approach":"Amount of rescue analgesic (ibuprofen 400 mg tablets) taken by the subject over the treatment period, assessed at end of 29 days."}

Secondary endpoints

• {"endpoint_text":"- Pre−post absolute change of each pain type associated with adenomyosis (non-menstrual pelvic pain, dysmenorrhea, dyspareunia) as documented on a VAS (in units) at each visit","definition_or_measurement_approach":"Absolute pre−post change per pain type measured by Visual Analogue Scale (VAS) at each visit."}
• {"endpoint_text":"- Clinical Global Impressions (CGI) scale after EoT on Day 30 (+4 days) visit)","definition_or_measurement_approach":"CGI assessment performed at End of Treatment visit (Day 30 ±4 days)."}
• {"endpoint_text":"- Patient Global Impression of Change (PGIC) scale after EoT on Day 30 (+4 days) visit)","definition_or_measurement_approach":"PGIC assessment performed at End of Treatment visit (Day 30 ±4 days)."}
• {"endpoint_text":"- Pre−post absolute change in the lesion(s) size after EoT on Day 30 (+4 days) visit)","definition_or_measurement_approach":"Lesion size measured at baseline and at End of Treatment visit (Day 30 ±4 days); absolute change calculated (method: imaging such as TVUS/MRI per protocol)."}
• {"endpoint_text":"- Pregnancy rate after the first in vitro fertilization cycle performed after a wash-out period of at least 30 days after the end of treatment","definition_or_measurement_approach":"Proportion of participants achieving pregnancy after first IVF cycle performed ≥30 days after end of treatment."}

Bulgaria

Earliest CTIS Part Ii Submission Date

18-03-2026

Latest Decision Or Authorization Date

03-04-2026

Processing Time Days

16

Number Of Sites

1

Number Of Participants

60

Primary sponsor

Full Name

CCDRD Cooperative Clinical Drug Research and Development AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Third parties

• {"country":"Bulgaria","full_name":"Milray AD","duties_or_roles":"sponsorDuties codes: 1","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Anapharm Europe S.L.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Bulgaria","full_name":"Biovet AD","duties_or_roles":"sponsorDuties codes: 14; 15 (15: blinding, labeling and release of study medication)","organisation_type":"Pharmaceutical company"}

Co-sponsors

• Nadezhda Reproductive Science OOD