A study to evaluate safety and processing by body of GDC-6988 in healthy adults receiving albuterol as a pretreatment medication

INTERVENTION: Participants in this study will receive a multiple ascending dose of GDC‐6988 or placebo as follows: Cohort A: Participants will receive 11.2 milligrams (mg) of GDC‐6988 (or placebo) as dry powder inhalation, administered using the Smart Dry Powder Inhaler (DPI), twice a day (BID) for 14 days. Starting on Day 8, participants will receive pre‐treatment dose of salbutamol up to Day 14. Cohort B: Participants will receive 22.4 mg of GDC‐6988 (or placebo) as dry powder inhalation, administered using DPI, BID for 14 days. Starting on Day 8, participants will receive pre‐treatment dose of salbutamol up to Day 14. Cohort C: Participants will receive 42 mg of GDC‐6988 (or placebo) as dry powder inhalation, administered using DPI, BID for 14 days. Starting on Day 8, participants will receive pre‐treatment dose of salbutamol up to Day 14. Cohort D (optional cohort): Participants will receive GDC‐6988 (dose TBD) or placebo as dry powder inhalation, administered using DPI, BID for 14 days. Starting on Day 8, participants will receive pre‐treatment dose of salbutamol up to Day 14. Participants will be randomised according to the master randomization list. The objective of the randomisation method is to define the TAI (Treatment Assignment Information) datasets based on the protocol. The Statistician is accountable for this step. The statistician will review the protocol and reach out to relevant personnel as required to identify the TAI datasets. The statistician will complete Roche's internal form, and send a copy to the TAI Gatekeeper (internal role within data management and separate from the study team), and other form recipients for use during the clinical trial and archive the form to the study TMF. The statistician will inform the Study Lead that the TAI datasets have CONDITION: Safety and pharmacokinetics of multiple ascending doses of GDC‐6988 with and without albuterol pretreatment in healthy adult subjects ; Not Applicable PRIMARY OUTCOME: 1. Percentage of participants with adverse events (AEs) and severity of AEs determined according to Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Paediatric Adverse Events (HHS 2017) from Day 1 up to 28 days after the final dose of study drug (up to approximately 42 days); 2. Percentage of participants with vital signs abnormalities as assessed by measuring respiratory rate, pulse rate, peripheral oxygen saturation, systolic and diastolic blood pressure and temperature from screening up to 28 days after the final dose of study drug (up to approximately 42 days); 3. Percentage of participants with laboratory test abnormalities measured using biological samples collected from screening up to 28 days after the final dose of study drug (up to approximately 42 days); 4. Percentage of participants with spirometry abnormalities measured using a spirometer from screening up to 28 days after the final dose of study drug (up to approximately 42 days) ; 5. Percentage of participants with oscillometry abnormalities measured using forced oscillometry technique (FOT) from Day 1 up to 28 days after the final dose of study drug (up to approximately 42 days); 6. Percentage of participants with electrocardiogram (ECG) abnormalities measured using 12‐Lead ECG recordings from screening up to 28 days after the final dose of study drug (up to approximately 42 days); 7. Percentage of participants with spirometry abnormalities after salbutamol (albuterol) pretreatment measured using a spirometer from Day 8 up to 28 days after the final dose of study drug (up to approximately 42 days); 8. Percentage of participants with oscillometry abnormalities after salbutamol (albuterol) pretreatment measured using FOT from Day 8 up to 28 days after the final dose of study drug (up to approximately 42 days) SECONDARY OUTCOME: 1. Plasma concentration of GDC‐6988 measured from blood samples taken at specific timepoints pre‐dose and post‐dose from Day 1 up to 28 days after the final dose of study drug (up to approximately 42 days) ; 2. Percentage of participants with device deficiencies measured based on the ISO 14155:2020, device deficiency definition from Day 1 up to 28 days after the final dose of study drug (up to approximately 42 days) ; 3. Relationship between GDC‐6988 exposure and AEs determined according to DAIDS Table for Grading the Severity of Adult and Paediatric Adverse Events (HHS 2017) from Day 1 up to 28 days after the final dose of study drug (up to approximately 42 days) INCLUSION CRITERIA: 1. Age 18 ‐ 55 years at time of signing Informed Consent Form 2. Body mass inde Xof 18 ‐ 32 kilograms per square metre (kg/m²) at screening 3. Body temperature of 35°C ‐ 37.5°C at screening and at Day‐1 4. Systolic blood pressure of 90 ‐ 150 millimetres of mercury (mmHg) and diastolic blood pressure of 50 ‐ 95 mmHg at screening and at Day‐1. Blood pressure should be measured while the participant is in a seated position. 5. Forced expiratory volume in 1 second (FEV1) >80% of predicted at screening and at Day‐1 6. Forced vital capacity (FVC) >2.0 L by spirometry at screening