Trial Outcomes & Findings for A Study To Evaluate The Efficacy, Safety, Pharmacokinetics, And Pharmacodynamic Effects Of GDC-6599 In Patients With Chronic Cough (NCT NCT05660850)

Last Updated: 2025-12-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

49 participants

Primary outcome timeframe

Baseline and Day 14 of Periods 1 and 2

Results posted on

2025-12-16

Participant Flow

A total of 49 participants with chronic cough took part in the study at 22 investigative sites across Australia, Canada, the United States, and the United Kingdom from 22 March 2023 to 20 October 2024. The study was terminated due to the sponsor's decision to discontinue the clinical development of GDC-6599.

This study had 2 parts: Part A (main study): chronic refractory cough (CRC) with asthma with/without atopy \& unexplained chronic cough (UCC); and Part B (substudy): CRC with chronic obstructive pulmonary disease (COPD) with/without chronic bronchitis (CB). Participants were randomized in 1:1 ratio into 2 crossover sequences (14-day Treatment Periods 1 and 2) to receive GDC-6599 and placebo and were then followed up for safety during the 28-day Safety Follow-up Period.

Participant milestones

Participant milestones
Measure	Part A: GDC-6599 - Placebo Participants with CRC-asthma with/without atopy, and UCC received GDC-6599, 50 milligrams (mg) tablets, orally, twice a day (BID) for 14 days in Period 1. Following a 14-day washout period, participants received GDC-6599 matching placebo, BID for 14 days in Period 2.	Part A: Placebo - GDC-6599 Participants with CRC-asthma with/without atopy, and UCC received GDC-6599 matching placebo tablets, orally, BID for 14 days in Period 1. Following a 14-day washout period, participants received GDC-6599, 50 mg, BID for 14 days in Period 2.	Part B: GDC-6599 - Placebo Participants with CRC-COPD with/without CB received GDC-6599, 50 mg tablets, orally, BID for 14 days in Period 1. Following a 14-day washout period, participants received GDC-6599 matching placebo, orally, BID for 14 days in Period 2.	Part B: Placebo - GDC-6599 Participants with CRC-COPD with/without CB received GDC-6599 matching placebo tablets, orally, BID for 14 days in Period 1. Following a 14-day washout period, participants received GDC-6599, 50 mg, BID for 14 days in Period 2.
Treatment Period 1 STARTED	24	23	1	1
Treatment Period 1 COMPLETED	24	23	1	1
Treatment Period 1 NOT COMPLETED	0	0	0	0
Treatment Period 2 STARTED	24	23	1	1
Treatment Period 2 COMPLETED	23	23	1	1
Treatment Period 2 NOT COMPLETED	1	0	0	0
Safety Follow-up Period STARTED	24	23	1	1
Safety Follow-up Period COMPLETED	24	23	1	1
Safety Follow-up Period NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A: GDC-6599 - Placebo Participants with CRC-asthma with/without atopy, and UCC received GDC-6599, 50 milligrams (mg) tablets, orally, twice a day (BID) for 14 days in Period 1. Following a 14-day washout period, participants received GDC-6599 matching placebo, BID for 14 days in Period 2.	Part A: Placebo - GDC-6599 Participants with CRC-asthma with/without atopy, and UCC received GDC-6599 matching placebo tablets, orally, BID for 14 days in Period 1. Following a 14-day washout period, participants received GDC-6599, 50 mg, BID for 14 days in Period 2.	Part B: GDC-6599 - Placebo Participants with CRC-COPD with/without CB received GDC-6599, 50 mg tablets, orally, BID for 14 days in Period 1. Following a 14-day washout period, participants received GDC-6599 matching placebo, orally, BID for 14 days in Period 2.	Part B: Placebo - GDC-6599 Participants with CRC-COPD with/without CB received GDC-6599 matching placebo tablets, orally, BID for 14 days in Period 1. Following a 14-day washout period, participants received GDC-6599, 50 mg, BID for 14 days in Period 2.
Treatment Period 2 Study Terminated by Sponsor	1	0	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: GDC-6599 - Placebo n=24 Participants Participants with CRC-asthma with/without atopy, and UCC received GDC-6599, 50 milligrams (mg) tablets, orally, twice a day (BID) for 14 days in Period 1. Following a 14-day washout period, participants received GDC-6599 matching placebo, BID for 14 days in Period 2.	Part A: Placebo - GDC-6599 n=23 Participants Participants with CRC-asthma with/without atopy, and UCC received GDC-6599 matching placebo tablets, orally, BID for 14 days in Period 1. Following a 14-day washout period, participants received GDC-6599, 50 mg, BID for 14 days in Period 2.	Part B: GDC-6599 - Placebo n=1 Participants Participants with CRC-COPD with/without CB received GDC-6599, 50 mg tablets, orally, BID for 14 days in Period 1. Following a 14-day washout period, participants received GDC-6599 matching placebo, orally, BID for 14 days in Period 2.	Part B: Placebo - GDC-6599 n=1 Participants Participants with CRC-COPD with/without CB received GDC-6599 matching placebo tablets, orally, BID for 14 days in Period 1. Following a 14-day washout period, participants received GDC-6599, 50 mg, BID for 14 days in Period 2.	Total n=49 Participants Total of all reporting groups
Age, Continuous	62.1 years STANDARD_DEVIATION 9.1 • n=6 Participants	58.5 years STANDARD_DEVIATION 12.8 • n=5 Participants	70.0 years STANDARD_DEVIATION NA • n=5 Participants	68.0 years STANDARD_DEVIATION NA • n=387 Participants	60.7 years STANDARD_DEVIATION 11.0 • n=18 Participants
Sex: Female, Male Female	13 Participants n=6 Participants	17 Participants n=5 Participants	1 Participants n=5 Participants	1 Participants n=387 Participants	32 Participants n=18 Participants
Sex: Female, Male Male	11 Participants n=6 Participants	6 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=387 Participants	17 Participants n=18 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=6 Participants	3 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=387 Participants	7 Participants n=18 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=6 Participants	20 Participants n=5 Participants	1 Participants n=5 Participants	1 Participants n=387 Participants	42 Participants n=18 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=387 Participants	0 Participants n=18 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=387 Participants	1 Participants n=18 Participants
Race (NIH/OMB) Asian	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=387 Participants	0 Participants n=18 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=387 Participants	0 Participants n=18 Participants
Race (NIH/OMB) Black or African American	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=387 Participants	0 Participants n=18 Participants
Race (NIH/OMB) White	23 Participants n=6 Participants	23 Participants n=5 Participants	1 Participants n=5 Participants	1 Participants n=387 Participants	48 Participants n=18 Participants
Race (NIH/OMB) More than one race	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=387 Participants	0 Participants n=18 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=387 Participants	0 Participants n=18 Participants
Cohorts CRC Asthma Atopic	4 Participants n=6 Participants	3 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=387 Participants	7 Participants n=18 Participants
Cohorts CRC Asthma Non-Atopic	4 Participants n=6 Participants	5 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=387 Participants	9 Participants n=18 Participants
Cohorts UCC	16 Participants n=6 Participants	15 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=387 Participants	31 Participants n=18 Participants
Cohorts CRC COPD	0 Participants n=6 Participants	0 Participants n=5 Participants	1 Participants n=5 Participants	1 Participants n=387 Participants	2 Participants n=18 Participants

PRIMARY outcome

Timeframe: Baseline and Day 14 of Periods 1 and 2

Population: ITT population included all participants who received any amount of GDC-6599 or placebo. Number analyzed is the number of participants with data available for analysis at the specified timepoint. As prespecified in the protocol participants were grouped according to the treatment received in Part A to compare results between GDC-6599 \& placebo regardless of treatment period \& disease cohort.

Outcome measures

Outcome measures
Measure	GDC-6599 n=47 Participants Participants received GDC-6599, 50 mg tablets, orally, BID for 14 days in Period 1 or Period 2.	Placebo n=47 Participants Participants received GDC-6599 matching placebo tablets, orally, BID for 14 days in Period 1 or Period 2.
Part A: Cough Frequency Per Hour, Assessed Objectively Over 24 Hours Using VitaloJAK® Cough Recorder Baseline	14.88 coughs/hour Standard Deviation NA NA= Geometric SD = 3.67	17.30 coughs/hour Standard Deviation NA NA= Geometric SD = 3.00
Part A: Cough Frequency Per Hour, Assessed Objectively Over 24 Hours Using VitaloJAK® Cough Recorder Day 14	12.61 coughs/hour Standard Deviation NA NA= Geometric SD = 3.70	13.21 coughs/hour Standard Deviation NA NA= Geometric SD = 3.46

SECONDARY outcome

Timeframe: Baseline to Day 14 of Periods 1 and 2

Population: ITT population included all participants who received any amount of GDC-6599 or placebo. Overall number analyzed is the number of participants with data available for analysis. As prespecified in the protocol participants were grouped according to the treatment received in Part A to compare results between GDC-6599 \& placebo regardless of treatment period \& disease cohort.

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.

Outcome measures

Outcome measures
Measure	GDC-6599 n=43 Participants Participants received GDC-6599, 50 mg tablets, orally, BID for 14 days in Period 1 or Period 2.	Placebo n=45 Participants Participants received GDC-6599 matching placebo tablets, orally, BID for 14 days in Period 1 or Period 2.
Part A: Change From Baseline in the Severity of Cough, as Assessed Using Participant-reported Cough Severity Visual Analog Scale (VAS) Scores	-11.218 score on a scale Standard Deviation 17.408	-9.642 score on a scale Standard Deviation 16.560

SECONDARY outcome

Timeframe: Baseline to Day 14 of Periods 1 and 2

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.

Outcome measures

Outcome measures
Measure	GDC-6599 n=43 Participants Participants received GDC-6599, 50 mg tablets, orally, BID for 14 days in Period 1 or Period 2.	Placebo n=45 Participants Participants received GDC-6599 matching placebo tablets, orally, BID for 14 days in Period 1 or Period 2.
Part A: Change From Baseline in the Severity of Cough, as Assessed Using Participant-reported Cough Severity Numeric Response Scale (NRS) Scores	-1.237 score on a scale Standard Deviation 1.676	-1.022 score on a scale Standard Deviation 1.560

SECONDARY outcome

Timeframe: From signing of informed consent form (ICF) until 28 days after the final dose of study drug (up to approximately 16 weeks)

Population: Safety population included all randomized participants who received at least one dose of study drug. As prespecified in the protocol participants in Part A and Part B were grouped according to the treatment received to compare results between GDC-6599 \& placebo regardless of treatment period \& disease cohort.

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.

Outcome measures

Outcome measures
Measure	GDC-6599 n=49 Participants Participants received GDC-6599, 50 mg tablets, orally, BID for 14 days in Period 1 or Period 2.	Placebo n=49 Participants Participants received GDC-6599 matching placebo tablets, orally, BID for 14 days in Period 1 or Period 2.
Number of Participants With Adverse Events (AEs)	18 Participants	13 Participants

SECONDARY outcome

Timeframe: Predose and 3 hours post dose on Days 1 and 14 of Periods 1 and 2 and Day 71 (Safety Follow-up Visit)

Population: Pharmacokinetic (PK) population included all participants with sufficient data to enable estimation of key parameters with participants grouped according to treatment received. Number analyzed is the number of participants with data available for analysis at the specified time point. As prespecified in the protocol participants in Part A and Part B were grouped according to the sequence in which they received treatment regardless of treatment period \& disease cohort.

Outcome measures

Outcome measures
Measure	GDC-6599 n=25 Participants Participants received GDC-6599, 50 mg tablets, orally, BID for 14 days in Period 1 or Period 2.	Placebo n=24 Participants Participants received GDC-6599 matching placebo tablets, orally, BID for 14 days in Period 1 or Period 2.
Plasma Concentration of GDC-6599 3 Hour Post dose on Day 1 Period 1	404 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 71.4	0.250 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation NA The geometric coefficient of variation was not estimable as samples were BLQ.
Plasma Concentration of GDC-6599 Predose on Day 14 Period 1	364 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 126.4	0.250 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation NA The geometric coefficient of variation was not estimable as samples were BLQ.
Plasma Concentration of GDC-6599 3 Hour Post dose on Day 14 Period 1	745 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 52.2	0.250 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation NA The geometric coefficient of variation was not estimable as samples were BLQ.
Plasma Concentration of GDC-6599 Predose on Day 1 Period 2	0.250 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation NA The geometric coefficient of variation was not estimable as samples were BLQ.	0.250 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation NA The geometric coefficient of variation was not estimable as samples were BLQ.
Plasma Concentration of GDC-6599 3 Hour Post dose on Day 1 Period 2	0.250 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation NA The geometric coefficient of variation was not estimable as samples were BLQ.	521 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 37.0
Plasma Concentration of GDC-6599 Predose on Day 14 Period 2	0.250 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation NA The geometric coefficient of variation was not estimable as samples were BLQ.	199 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 512.3
Plasma Concentration of GDC-6599 3 Hour Post dose on Day 14 Period 2	0.250 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation NA The geometric coefficient of variation was not estimable as samples were BLQ.	758 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 42.2
Plasma Concentration of GDC-6599 Day 71 (Safety Follow-up Visit)	0.250 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation NA The geometric coefficient of variation was not estimable as samples were BLQ.	0.250 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation NA The geometric coefficient of variation was not estimable as samples were BLQ.
Plasma Concentration of GDC-6599 Predose on Day 1 Period 1	NA nanograms per milliliter (ng/mL) Geometric Coefficient of Variation NA The geometric mean and geometric coefficient of variation were not estimable as samples were below the limit of quantification (BLQ).	NA nanograms per milliliter (ng/mL) Geometric Coefficient of Variation NA The geometric mean and geometric coefficient of variation were not estimable as samples were BLQ.

Adverse Events

GDC-6599

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Safety Follow-up

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	GDC-6599 n=49 participants at risk Participants received GDC-6599, 50 mg tablets, orally, BID for 14 days in Period 1 or Period 2.	Placebo n=49 participants at risk Participants received GDC-6599 matching placebo tablets, orally, BID for 14 days in Period 1 or Period 2.	Safety Follow-up n=49 participants at risk Participants were assessed for an additional 28 days for safety after receiving the last dose of study treatment or treatment discontinuation visit.
Nervous system disorders Headache	10.2% 5/49 • Number of events 5 • From signing of ICF until 28 days after the final dose of study drug (up to approximately 16 weeks) Safety population included all randomized participants who received at least one dose of study drug. treatment. As prespecifid in the protocol participants in Parts A and B were grouped according to the treatment received to compare results between GDC-6599 \& placebo regardless of treatment period \& disease cohort.	4.1% 2/49 • Number of events 3 • From signing of ICF until 28 days after the final dose of study drug (up to approximately 16 weeks) Safety population included all randomized participants who received at least one dose of study drug. treatment. As prespecifid in the protocol participants in Parts A and B were grouped according to the treatment received to compare results between GDC-6599 \& placebo regardless of treatment period \& disease cohort.	0.00% 0/49 • From signing of ICF until 28 days after the final dose of study drug (up to approximately 16 weeks) Safety population included all randomized participants who received at least one dose of study drug. treatment. As prespecifid in the protocol participants in Parts A and B were grouped according to the treatment received to compare results between GDC-6599 \& placebo regardless of treatment period \& disease cohort.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER