Early Study on Tamoxifen Safety/Tolerability in Cystic Fibrosis Patients Unable to Use CFTR Modulators.

Korábbi kezelés

• Patients on any CFTR modulator therapy
• Pulmonary exacerbations within 3 weeks before Day 1 (first dose of study drug)
• Changes in therapy for lung disease within 3 weeks before Day 1 (first dose of study drug)
• Participation in a clinical study where an investigational drug was administered within 30 days prior to enrollment in the study or 5 half-lives of the study drug, whichever is longer

Más betegség

• Family and/or personal history of thromboembolism and thromboembolic conditions up to 1st-degree relatives
• History of solid organ or hematopoietic transplant
• History of hypersensitivity to the study drug or drugs of similar chemical classes or any excipients
• History of malignancy in any organ system (other than localized basal cell carcinoma of the skin) in the last 5 years
• Any surgical or medical condition that may significantly alter the absorption, distribution, metabolism, or excretion of drugs, or that may jeopardize the subject in case of participation in the study
• History of immunodeficiency diseases
• History of drug or alcohol abuse
• History of any disease or condition that, in the investigator's opinion, could confound the study results
• Female patients of childbearing potential who do not use adequate contraception. A woman is considered of childbearing potential (WOCBP), i.e., fertile, after menarche and until reaching post-menopause, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as the absence of menstruation for 12 months without an alternative medical cause. An elevated follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormone replacement therapy. However, in the absence of 12 months of menstrual cycle, a single FSH measurement is not sufficient.* *Low failure rate contraceptive methods (less than 1% per year) if used consistently, including: some intrauterine devices, abstinence, or vasectomized partner. Contraception must be maintained until 1 month after the last visit.

Laborértékek

• History or presence of prolonged QT interval (QTcB > 450 msec)
• Hemoglobin levels < 9.0 g/dl
• Abnormal liver function, defined as ≥ 3 times the upper limit of normal (ULN) for any of the following: serum aspartate transaminase (AST), serum alanine transaminase (ALT), total bilirubin.

Egyéb

• Patients will be excluded if one or more of the following criteria are met at Visit 1:
• Documented hereditary thrombophilia (hypercoagulability), e.g., protein C, protein S, and antithrombin deficiency; factor V G169A Leiden, prothrombin G20210A (PT20210A), elevated factor VIII levels, hereditary dysfibrinogenemia
• Presence at baseline visit of endometrial polyps or vaginal symptoms (e.g., blood discharge, spotting, staining)
• Female patients who are pregnant or breastfeeding or who wish to become pregnant during the clinical study period and within one month after the end of the study

• Patients will be included if they meet all the following inclusion criteria at Visit 1:
• Subjects of both sexes, affected by cystic fibrosis, attending the CF Center in Verona
• Patients who do not have mutations currently eligible for therapy with CFTR modulator drugs
• Age 18 years or older
• Predicted forced expiratory volume in 1 second (ppFEV1) ≥ 40% and ≤ 90% (of the predicted value for people of their age, sex, and height) before bronchodilator administration
• Stable routine CF therapy in terms of dose and medication (inhaled antibiotic cycles, bronchodilator, anti-inflammatory, inhaled corticosteroid, physiotherapy technique/schedule) within 28 days prior to Day 1
• Clinically stable respiratory disease within 3 weeks before Day 1 (first dose of study drug)
• Subjects able to perform reliable and reproducible pulmonary function test maneuvers
• Subjects able to communicate well with the investigator, understand, and comply with the study requirements
• Female subjects must have a negative serum pregnancy test
• Sexually active subjects able to follow the contraceptive methods defined within the protocol (non-hormonal contraception) during the study and for 2 months after study discontinuation
• Signed informed consent for participation in the study and for the processing of personal data.