A Study To Evaluate The Efficacy, Safety, Pharmacokinetics, And Pharmacodynamic Effects Of GDC-6599 In Patients With Chronic Cough

This Phase IIa, multicenter, randomized, double-blind, placebo-controlled, crossover study will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamic (PD) effects of GDC-6599 compared with placebo in patients with a history of chronic cough.

Inclusion Criteria:Previous diagnosis of CRC, despite optimized treatment for asthma or COPD, or UCC for at least 1 yearChest X-ray or computed tomography (CT) scan thorax within 5 years prior to screening visit that confirms the absence of any clinically significant abnormality contributing to the chronic cough in the opinion of the investigatorCough severity VAS score ≥ 40 at screening visitPre-bronchodilator forced expiratory volume in 1 second (FEV1) ≥ 60% of predicted at screening"Mannitol CDR ≥ 12 coughs/100 mg determined at screening visit mannitol challenge testFor women of childbearing potential: agreement to remain abstinent or use contraception For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating spermInclusion Criteria for Patients with CRC with Atopic Asthma or Patients with CRC with Non-Atopic Asthma (Part A)Physician diagnosis of asthma for ≥ 12 months based upon GINA STEP 2-5Stable treatment with ICS therapy (GINA STEP 2) or ICS therapy and at least one additional controller (GINA STEP 3- 5) for ≥ 3 monthsPatients with atopic asthma (n = 20), based upon historic record of positive test for atopy (if available), or confirmed at screening by positive fluorescence enzyme immunoassay for specific IgE against at least one of the following five perennial aeroallergens: animal (cat dander, dog dander, cockroach), dust mite (Dermatophagoides farinae, Dermatophagoides pteronyssinus), and mold mixPatients with non-atopic asthma (n = 20), based upon historic record of negative test for atopy (if available), or confirmed at screening by negative ImmunoCAP test result for all five perennial aeroallergens: animal (cat dander, dog dander, cockroach), dust mite (Dermatophagoides farinae, Dermatophagoides pteronyssinus), and mold mix, and relevant local allergens, and no history of symptoms suggesting atopyNever or former smoker (≥ 6 months prior to screening) with < 20 pack-years or equivalent historyInclusion Criteria for Patients with CRC COPD-CB or Patients with CRC COPD (Part B)Diagnosis of COPD GOLD I-II ± CBStable background treatment consisting of a bronchodilator medication and or stable ICS therapy for ≥ 12 weeks prior to screening visitFormer smoker with ≥ 10 pack-years or equivalent history within 6 months of screeningPost-bronchodilator FEV1/ forced vital capacity (FVC) ratio ≤ 0.70 at screeningChest X-ray or CT scan within 6 months prior to screening visit or during the screening period (prior to randomization [Study Visit 2]), that confirms the absence of clinically significant lung disease besides COPDExclusion Criteria:Pregnant or breastfeeding, or intention of becoming pregnant during the study or within 28 days after the final dose of GDC-6599History of diagnosed bleeding diathesis or easy bruising or bleedingPost-bronchodilator FEV1/ FVC ratio < 0.60 at screening visit (patients with CRC asthma and UCC only: Part A)History of significant hepatic impairmentHistory of aspiration or recurrent pneumoniaRespiratory infection (including upper respiratory infection) within 8 weeks prior to screeningTreatment with any strong inhibitor or inducer of CYP3A within 28 days or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drugTreatment with angiotensin-converting enzyme (ACE) inhibitor within 12 weeks prior to screening (Study Visit 1) through completion of the studyTreatment with opioids (including codeine), pregabalin, gabapentin, amitriptyline, or nortriptyline for the treatment of cough within 2 weeks prior to screening (Study Visit 1) through completion of the studyTreatment with cough suppressant medication within 2 weeks prior to screening (Study Visit 1) through completion of the studyKnown coronavirus 2019 (COVID-19) infection, persistent symptoms of known prior COVID-19 infection, and/or known positive COVID-19 test within at least 8 weeks prior to screening and randomizationClinical laboratory value outside the reference range for the test laboratory at screeningAny serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the studyHistory of malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix or non-melanoma skin carcinoma