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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
49
GDC-6599 will be administered Days 1- 14 and on Days 29-42 as film-coated tablets
GDC-6599-matching placebo will be administered Days 1- 14 and on Days 29- 42. as film-coated tablets
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
Southern California Institute For Respiratory
Los Angeles, California, United States
California Medical Research Associates, Inc.
Northridge, California, United States
Pioneer Clinical Studies
Coral Gables, Florida, United States
Mayo Clinic
Rochester, Minnesota, United States
Clinical Research Associates Of Central Pa , Llc
DuBois, Pennsylvania, United States
ADAC Research PA
Greenville, South Carolina, United States
Pharmaceutical Research & Consulting, Inc.
Dallas, Texas, United States
Bellingham Asthma, Allergy & Immunology
Bellingham, Washington, United States
TrialsWest Pty Ltd
Spearwood, Western Australia, Australia
McMaster University Medical Centre
Hamilton, Ontario, Canada
...and 8 more locations
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.
Time frame: Baseline and Day 14 of Periods 1 and 2
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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: Predose and 3 hours post dose on Days 1 and 14 of Periods 1 and 2 and Day 71 (Safety Follow-up Visit)
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