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

NCT05660850 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: GA43590
• Study Type: interventional
• Target: 49
• Locations: 4 countries
• Sites: 18

Brief Summary

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.

Conditions

CRC With Atopic Asthma; Unexplained Chronic Cough; CRC With Chronic Obstructive Pulmonary Disease; CRC With Chronic Obstructive Pulmonary Disease With Chronic Bronchitis; Chronic Refractory Cough (CRC) With Non-atopic Asthma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Part A: Change From Baseline in the Severity of Cough, as Assessed Using Participant-reported Cough Severity Visual Analog Scale (VAS) Scores

  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

  Baseline to Day 14 of Periods 1 and 2

• Number of Participants With Adverse Events (AEs)

  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)

Study Arms (5)

Part A: CRC Asthma atopic

EXPERIMENTAL

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; Other: GDC-6599-matching placebo; Diagnostic Test: Mannitol

Part A: CRC Asthma non-atopic

EXPERIMENTAL

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; Other: GDC-6599-matching placebo; Diagnostic Test: Mannitol

Part A: Unexplained Chronic Cough

EXPERIMENTAL

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; Other: GDC-6599-matching placebo; Diagnostic Test: Mannitol

Part B: Chronic Refractory Cough with Chronic Obstructive Pulmonary Disease

EXPERIMENTAL

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; Other: GDC-6599-matching placebo; Diagnostic Test: Mannitol

Part B: Chronic Refractory Cough with Chronic Obstructive Pulmonary Disease with Chronic Bronchitis

EXPERIMENTAL

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; Other: GDC-6599-matching placebo; Diagnostic Test: Mannitol

Interventions

Mannitol DIAGNOSTIC_TEST

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

Part A: CRC Asthma atopic; Part A: CRC Asthma non-atopic; Part A: Unexplained Chronic Cough; Part B: Chronic Refractory Cough with Chronic Obstructive Pulmonary Disease; Part B: Chronic Refractory Cough with Chronic Obstructive Pulmonary Disease with Chronic Bronchitis

GDC-6599 DRUG

GDC-6599 will be administered Days 1- 14 and on Days 29-42 as film-coated tablets

Also known as: RO7441345

Part A: CRC Asthma atopic; Part A: CRC Asthma non-atopic; Part A: Unexplained Chronic Cough; Part B: Chronic Refractory Cough with Chronic Obstructive Pulmonary Disease; Part B: Chronic Refractory Cough with Chronic Obstructive Pulmonary Disease with Chronic Bronchitis

GDC-6599-matching placebo OTHER

GDC-6599-matching placebo will be administered Days 1- 14 and on Days 29- 42. as film-coated tablets

Part A: CRC Asthma atopic; Part A: CRC Asthma non-atopic; Part A: Unexplained Chronic Cough; Part B: Chronic Refractory Cough with Chronic Obstructive Pulmonary Disease; Part B: Chronic Refractory Cough with Chronic Obstructive Pulmonary Disease with Chronic Bronchitis

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (18)

Southern California Institute For Respiratory

Los Angeles, California, 90048, United States

Location

California Medical Research Associates, Inc.

Northridge, California, 91324, United States

Location

Pioneer Clinical Studies

Coral Gables, Florida, 33134, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Clinical Research Associates Of Central Pa , Llc

DuBois, Pennsylvania, 15801-2277, United States

Location

ADAC Research PA

Greenville, South Carolina, 29607, United States

Location

Pharmaceutical Research & Consulting, Inc.

Dallas, Texas, 75231, United States

Location

Bellingham Asthma, Allergy & Immunology

Bellingham, Washington, 98225, United States

Location

TrialsWest Pty Ltd

Spearwood, Western Australia, 6163, Australia

Location

McMaster University Medical Centre

Hamilton, Ontario, L8N 3Z5, Canada

Location

Diex Recherche - Québec - HyperCore - PPDS

Québec, Canada

Location

Castle Hill Hospital

Cottingham, North Humberside, HU16 5JQ, United Kingdom

Location

Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

Location

West Walk Surgery

Bristol, BS37 4AX, United Kingdom

Location

Royal Infirmary of Edinburgh

Edinburgh, EH16 4SA, United Kingdom

Location

Glenfield Hospital

Leicester, LE3 9QP, United Kingdom

Location

Kings College Hospital

London, SE5 9RS, United Kingdom

Location

Queen Anne Street Medical Centre

London, W1G 8HU, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 41124168 DERIVED

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Genetech

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2022
• First Posted: December 21, 2022
• Study Start: March 22, 2023
• Primary Completion: October 20, 2024
• Study Completion: October 20, 2024
• Last Updated: December 16, 2025
• Results First Posted: December 16, 2025

Record last verified: 2025-11

Locations

US (8); GB (7); CA (2); AU (1)