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

NCT ID: NCT05660850

Last Updated: 2025-12-16

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

49 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-03-22

Study Completion Date

2024-10-20

Brief Summary

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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.

Detailed Description

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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).

Conditions

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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

Group Type EXPERIMENTAL

GDC-6599

Intervention Type DRUG

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

GDC-6599-matching placebo

Intervention Type OTHER

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

Mannitol

Intervention Type 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 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

Group Type EXPERIMENTAL

GDC-6599

Intervention Type DRUG

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

GDC-6599-matching placebo

Intervention Type OTHER

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

Mannitol

Intervention Type 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: 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

Group Type EXPERIMENTAL

GDC-6599

Intervention Type DRUG

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

GDC-6599-matching placebo

Intervention Type OTHER

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

Mannitol

Intervention Type 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 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.

Group Type EXPERIMENTAL

GDC-6599

Intervention Type DRUG

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

GDC-6599-matching placebo

Intervention Type OTHER

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

Mannitol

Intervention Type 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 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.

Group Type EXPERIMENTAL

GDC-6599

Intervention Type DRUG

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

GDC-6599-matching placebo

Intervention Type OTHER

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

Mannitol

Intervention Type 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

Interventions

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GDC-6599

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

Intervention Type DRUG

GDC-6599-matching placebo

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

Intervention Type OTHER

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

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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RO7441345

Eligibility Criteria

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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


* 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
* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Genetech

Locations

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Southern California Institute For Respiratory

Los Angeles, California, United States

Site Status

California Medical Research Associates, Inc.

Northridge, California, United States

Site Status

Pioneer Clinical Studies

Coral Gables, Florida, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Clinical Research Associates Of Central Pa , Llc

DuBois, Pennsylvania, United States

Site Status

ADAC Research PA

Greenville, South Carolina, United States

Site Status

Pharmaceutical Research & Consulting, Inc.

Dallas, Texas, United States

Site Status

Bellingham Asthma, Allergy & Immunology

Bellingham, Washington, United States

Site Status

TrialsWest Pty Ltd

Spearwood, Western Australia, Australia

Site Status

McMaster University Medical Centre

Hamilton, Ontario, Canada

Site Status

Diex Recherche - Québec - HyperCore - PPDS

Québec, , Canada

Site Status

Castle Hill Hospital

Cottingham, North Humberside, United Kingdom

Site Status

Belfast City Hospital

Belfast, , United Kingdom

Site Status

West Walk Surgery

Bristol, , United Kingdom

Site Status

Royal Infirmary of Edinburgh

Edinburgh, , United Kingdom

Site Status

Glenfield Hospital

Leicester, , United Kingdom

Site Status

Kings College Hospital

London, , United Kingdom

Site Status

Queen Anne Street Medical Centre

London, , United Kingdom

Site Status

Countries

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United States Australia Canada United Kingdom

References

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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.

Reference Type DERIVED
PMID: 41124168 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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GA43590

Identifier Type: -

Identifier Source: org_study_id