Ensayos clínicos

Inclusion Criteria:

• Women and Men between 18 and 80 years of age, inclusive.
• Chest radiograph or computed tomography (CT) of the thorax within the last 1 year not demonstrating any abnormality considered to be significantly contributing to the refractory chronic cough in the opinion of the Principal Investigator and Attenua Medical Monitor.
• Have a diagnosis of refractory chronic cough or unexplained cough for at least one year.
• Have a score of ≥ 40mm on the Cough Severity VAS at Screening.
• Have an awake cough frequency ≥10 coughs/hour, as assessed using the VitaloJAK during the Screening Period.
• Women of child-bearing potential must use 2 forms of acceptable birth control and make no donation of eggs from Screening through the Follow-Up Visit.
• Acceptable birth control methods include established use of oral, injected, or implanted hormonal methods of contraception; intrauterine device (IUD) or intrauterine system (IUS); tubal ligation; or male sterilization. Double-barrier method (diaphragm for female subject and condom for male partner with spermicidal) satisfies the requirement for 2 forms of acceptable birth control.
• When in line with the preferred life style of the subject, true and complete abstinence (not periodic abstinence) is acceptable.
• Male subjects and their partners of child-bearing potential must use 2 methods of acceptable birth control, 1 of which must be a barrier method, and make no donation of sperm from Screening until 3 months after the last dose of study drug.
• Have provided written informed consent.
• Are willing and able to comply with all aspects of the protocol.

Exclusion Criteria

• Current smoker (cigarettes or e-cigarettes), individuals who have given up smoking within the past 12 months or individuals who use nicotine patches, nicotine gum, or any other nicotine supplements.
• Treatment with an ACE-inhibitor as the potential cause of a subject’s cough, or requiring treatment with an ACE-inhibitor during the study or within 12 weeks prior to the Baseline Visit (Day -1).
• FEV1/FVC < 60%.
• History of upper or lower respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit (Day -1).
• History of cystic fibrosis.
• History of opioid use (for chronic cough) within 1 week of the Baseline Visit (Day -1).
• Requiring concomitant therapy with prohibited medications (see Section 5.6.1).
• Treatment with strong CYP3A4 inhibitors or inducers within 4 weeks prior to the Baseline Visit (Day -1).
• Body mass index (BMI) <18 kg/m2 or ≥ 40 kg/m2.
• Treatment with any investigational therapy within 4 weeks (investigational biologic therapies within 8 weeks) prior to the Baseline Visit (Day -1).
• Serum creatinine, total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2x the upper limit of normal (ULN) during screening.
• Positive test for any drug of abuse (certain drugs are acceptable for non-cough indications).
• Clinically significant laboratory or ECG abnormality that could be a safety issue in the study, including QT using Bazett’s or Fredericia’s correction of QT interval (QTcB or QTcF) > 450 msec for males and > 470 msec for females.
• History of malignancy within 5 years prior to the Baseline Visit (Day -1), with the exception of completely treated and non-metastatic basal cell carcinoma or completely treated and non-metastatic squamous cell carcinoma of the skin.
• Any known psychiatric diagnosis meeting DSM-5 criteria which may confound the assessment of bradanicline safety or efficacy, or interfere with the subject’s ability to comply with protocol-mandated activities, within 3 years prior to randomization. Examples of such DSM-5 diagnoses include but are not limited to major depressive disorder, bipolar disorder, schizophrenia, psychotic disorder, intellectual disability, severe alcohol use disorder, cannabis dependence or abuse.
• Active hepatitis infection.
• History of human immunodeficiency virus (HIV) infection.
• History of hypersensitivity to bradanicline or any of its components.
• Currently pregnant or breastfeeding female subject.
• Presence of any medical condition or disability that, in the investigator’s or the Attenua Medical Monitor’s opinion, could interfere with the assessment of safety or efficacy in this trial or compromise the safety of the subject.
• Planned or anticipated major surgical procedure or other activity that would interfere with the subject’s ability to comply with protocol-mandated assessments (e.g., extended travel) during the subject’s participation in the study.