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

A Phase IIa, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Crossover 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.

Study Overview

• Status: Completed
• Conditions: Chronic Refractory Cough (CRC) With Non-atopic Asthma; CRC With Atopic Asthma; Unexplained Chronic Cough; CRC With Chronic Obstructive Pulmonary Disease; CRC With Chronic Obstructive Pulmonary Disease With Chronic Bronchitis
• Intervention / Treatment: Drug: GDC-6599; Other: GDC-6599-matching placebo; Diagnostic test: Mannitol

Detailed Description

The main study (Part A) enrolled participants with chronic refractory cough (CRC) with asthma with/without atopy as well as participants with unexplained chronic cough (UCC); the substudy (Part B) enrolled participants with chronic obstructive pulmonary disease (COPD) with/without chronic bronchitis (CB).

The main objective of the study was was to evaluate the efficacy of GDC-6599, as compared with placebo, in participants with CRC with asthma or UCC (i.e. across all participants in main study - Part A, regardless of the disease background).

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Spearwood, Western Australia, Australia, 6163
      • TrialsWest Pty Ltd
• Canada
  • Québec, Canada
    • Diex Recherche - Québec - HyperCore - PPDS
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University Medical Centre
• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • Belfast City Hospital
  • Bristol, United Kingdom, BS37 4AX
    • West Walk Surgery
  • Edinburgh, United Kingdom, EH16 4SA
    • Royal Infirmary of Edinburgh
  • Leicester, United Kingdom, LE3 9QP
    • Glenfield Hospital
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital
  • London, United Kingdom, W1G 8HU
    • Queen Anne Street Medical Centre
  • North Humberside
    • Cottingham, North Humberside, United Kingdom, HU16 5JQ
      • Castle Hill Hospital
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Southern California Institute For Respiratory
    • Northridge, California, United States, 91324
      • California Medical Research Associates, Inc.
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Pioneer Clinical Studies
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Pennsylvania
    • DuBois, Pennsylvania, United States, 15801-2277
      • Clinical Research Associates Of Central Pa , Llc
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • ADAC Research PA
  • Texas
    • Dallas, Texas, United States, 75231
      • Pharmaceutical Research & Consulting, Inc.
  • Washington
    • Bellingham, Washington, United States, 98225
      • Bellingham Asthma, Allergy & Immunology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Previous diagnosis of CRC, despite optimized treatment for asthma or COPD, or UCC for at least 1 year
• Chest 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 investigator
• Cough severity VAS score ≥ 40 at screening visit
• Pre-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 test
• For 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 sperm

Inclusion 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 2-5
• Stable treatment with ICS therapy (GINA STEP 2) or ICS therapy and at least one additional controller (GINA STEP 3- 5) for ≥ 3 months
• Patients 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 mix
• Patients 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 atopy
• Never or former smoker (≥ 6 months prior to screening) with < 20 pack-years or equivalent history

Inclusion Criteria for Patients with CRC COPD-CB or Patients with CRC COPD (Part B)

• Diagnosis of COPD GOLD I-II ± CB
• Stable background treatment consisting of a bronchodilator medication and or stable ICS therapy for ≥ 12 weeks prior to screening visit
• Former smoker with ≥ 10 pack-years or equivalent history within 6 months of screening
• Post-bronchodilator FEV1/ forced vital capacity (FVC) ratio ≤ 0.70 at screening
• Chest 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 COPD

Exclusion Criteria:

• Pregnant or breastfeeding, or intention of becoming pregnant during the study or within 28 days after the final dose of GDC-6599
• History of diagnosed bleeding diathesis or easy bruising or bleeding
• Post-bronchodilator FEV1/ FVC ratio < 0.60 at screening visit (patients with CRC asthma and UCC only: Part A)
• History of significant hepatic impairment
• History of aspiration or recurrent pneumonia
• Respiratory infection (including upper respiratory infection) within 8 weeks prior to screening
• Treatment 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 drug
• Treatment with angiotensin-converting enzyme (ACE) inhibitor within 12 weeks prior to screening (Study Visit 1) through completion of the study
• Treatment 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 study
• Treatment with cough suppressant medication within 2 weeks prior to screening (Study Visit 1) through completion of the study
• Known 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 randomization
• Clinical laboratory value outside the reference range for the test laboratory at screening
• Any 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 study
• History of malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix or non-melanoma skin carcinoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: CRC Asthma atopic; Patients with CRC atopic asthma will be randomized in a 1:1 ratio to receive GDC-6599 or placebo for 14 days during the first study period (Treatment Period 1, Study Visits 2-4). Following a 14-day washout period, patients will cross over to the second study period (Treatment Period 2, Study Visits 5-7) and will receive the alternate treatment (GDC-6599 or placebo) for 14 days starting at Study Visit 5	Drug: GDC-6599; GDC-6599 will be administered Days 1- 14 and on Days 29-42 as film-coated tablets; Other Names: RO7441345; Other: GDC-6599-matching placebo; GDC-6599-matching placebo will be administered Days 1- 14 and on Days 29- 42. as film-coated tablets; Diagnostic test: Mannitol; Mannitol challenge tests will be performed during screening and at least 2.5 hours following study drug administration at Study Visits 2, 4, 5 and 7
Experimental: Part A: CRC Asthma non-atopic; Patients with CRC non-atopic asthma will be randomized in a 1:1 ratio to receive GDC-6599 or placebo for 14 days during the first study period (Treatment Period 1, Study Visits 2-4). Following a 14-day washout period, patients will cross over to the second study period (Treatment Period 2, Study Visits 5-7) and will receive the alternate treatment (GDC-6599 or placebo) for 14 days starting at Study Visit 5	Drug: GDC-6599; GDC-6599 will be administered Days 1- 14 and on Days 29-42 as film-coated tablets; Other Names: RO7441345; Other: GDC-6599-matching placebo; GDC-6599-matching placebo will be administered Days 1- 14 and on Days 29- 42. as film-coated tablets; Diagnostic test: Mannitol; Mannitol challenge tests will be performed during screening and at least 2.5 hours following study drug administration at Study Visits 2, 4, 5 and 7
Experimental: Part A: Unexplained Chronic Cough; Patients with Unexplained Chronic Cough will be randomized in a 1:1 ratio to receive GDC-6599 or placebo for 14 days during the first study period (Treatment Period 1, Study Visits 2-4). Following a 14-day washout period, patients will cross over to the second study period (Treatment Period 2, Study Visits 5-7) and will receive the alternate treatment (GDC-6599 or placebo) for 14 days starting at Study Visit 5	Drug: GDC-6599; GDC-6599 will be administered Days 1- 14 and on Days 29-42 as film-coated tablets; Other Names: RO7441345; Other: GDC-6599-matching placebo; GDC-6599-matching placebo will be administered Days 1- 14 and on Days 29- 42. as film-coated tablets; Diagnostic test: Mannitol; Mannitol challenge tests will be performed during screening and at least 2.5 hours following study drug administration at Study Visits 2, 4, 5 and 7
Experimental: Part B: Chronic Refractory Cough with Chronic Obstructive Pulmonary Disease; Patients with Chronic Obstructive Pulmonary Disease will be randomized in a 1:1 ratio to receive GDC-6599 or placebo for 14 days during the first study period (Treatment Period 1, Study Visits 2-4). Following a 14-day washout period, patients will cross over to the second study period (Treatment Period 2, Study Visits 5-7) and will receive the alternate treatment (GDC-6599 or placebo) for 14 days starting at Study Visit 5.	Drug: GDC-6599; GDC-6599 will be administered Days 1- 14 and on Days 29-42 as film-coated tablets; Other Names: RO7441345; Other: GDC-6599-matching placebo; GDC-6599-matching placebo will be administered Days 1- 14 and on Days 29- 42. as film-coated tablets; Diagnostic test: Mannitol; Mannitol challenge tests will be performed during screening and at least 2.5 hours following study drug administration at Study Visits 2, 4, 5 and 7
Experimental: Part B: Chronic Refractory Cough with Chronic Obstructive Pulmonary Disease with Chronic Bronchitis; Patients with Chronic Obstructive Pulmonary Disease with Chronic Bronchitis will be randomized in a 1:1 ratio to receive GDC-6599 or placebo for 14 days during the first study period (Treatment Period 1, Study Visits 2-4). Following a 14-day washout period, patients will cross over to the second study period (Treatment Period 2, Study Visits 5-7) and will receive the alternate treatment (GDC-6599 or placebo) for 14 days starting at Study Visit 5.	Drug: GDC-6599; GDC-6599 will be administered Days 1- 14 and on Days 29-42 as film-coated tablets; Other Names: RO7441345; Other: GDC-6599-matching placebo; GDC-6599-matching placebo will be administered Days 1- 14 and on Days 29- 42. as film-coated tablets; Diagnostic test: Mannitol; Mannitol challenge tests will be performed during screening and at least 2.5 hours following study drug administration at Study Visits 2, 4, 5 and 7

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Cough Frequency Per Hour, Assessed Objectively Over 24 Hours Using VitaloJAK® Cough Recorder	Cough numbers were assessed by the VitaloJAK semi-automated cough-monitoring system. The VitaloJAK device recorded ambulatory audio for 24 hours from two channels, a lapel microphone (air) and a chest-facing sensor (skin). A software algorithm removed non-cough sounds from the 24-hour audio recordings, compressing the files to less than 10% (on average) of the original length enabling manual analysis to be completed more quickly. The recordings were reviewed by trained Vitalograph analysts who counted individual explosive cough sounds, yielding hourly and 24-hour objective cough count (OCCs). Cough frequency was calculated as the total number of coughs for the full 24 hours recording minus coughs flagged within Mute, Flagged Area, Device Not Attached and Recording Ended Early events divided by the full 24 hours recording minus Mute, Flagged Area, Device Not Attached and Recording Ended Early event time. The standard deviation (SD) reported here is geometric SD.	Baseline and Day 14 of Periods 1 and 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Change From Baseline in the Severity of Cough, as Assessed Using Participant-reported Cough Severity Visual Analog Scale (VAS) Scores	Cough severity scores were assessed by the participants using VAS. The VAS was a single-item rating used for the subjective assessment of cough severity. Participants were asked to indicate the severity of their cough by marking a line on a scale between anchor statements of 'no cough' and 'worst cough'. The score was determined by measuring the distance on the line between the anchor and the participant's mark, providing a range of scores from 0-100. A higher score indicates greater severity.	Baseline to Day 14 of Periods 1 and 2
Part A: Change From Baseline in the Severity of Cough, as Assessed Using Participant-reported Cough Severity Numeric Response Scale (NRS) Scores	Cough severity scores were assessed by the participants using the NRS. Participants were asked to rate the severity of their cough in the last 24 hours from 0 (no cough) to 10 (worst cough). Higher scores indicates greater severity.	Baseline to Day 14 of Periods 1 and 2
Number of Participants With Adverse Events (AEs)	An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	From signing of informed consent form (ICF) until 28 days after the final dose of study drug (up to approximately 16 weeks)
Plasma Concentration of GDC-6599		Predose and 3 hours post dose on Days 1 and 14 of Periods 1 and 2 and Day 71 (Safety Follow-up Visit)

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Clinical Trials, Genetech

Publications and helpful links

General Publications

• Brown I, Tran T, Funwie A, Patel S, Dawson K, McKenzie M. Sexual orientation and gender identity data: An observational study assessing the feasibility of SOGI collection in clinical research and patient assistance programs. PLoS One. 2025 Oct 22;20(10):e0332805. doi: 10.1371/journal.pone.0332805. eCollection 2025.

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2023
• Primary Completion (Actual): October 20, 2024
• Study Completion (Actual): October 20, 2024

Study Registration Dates

• First Submitted: November 7, 2022
• First Submitted That Met QC Criteria: December 14, 2022
• First Posted (Actual): December 21, 2022

Study Record Updates

• Last Update Posted (Actual): December 16, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Immune System Diseases; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Respiration Disorders; Bronchial Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Signs and Symptoms, Respiratory; Chronic Cough; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Asthma; Cough; Bronchitis; Bronchitis, Chronic; Physiological Effects of Drugs; Diuretics; Natriuretic Agents; Diuretics, Osmotic; Mannitol
• Other Study ID Numbers: GA43590

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No