Safety and pharmacokinetics of multiple ascending doses of GDC-6988 with and without albuterol pretreatment in healthy adult subjects Not Applicable
Conditions
Interventions
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 in
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 18 - 55 years at time of signing Informed Consent Form 2. Body mass index of 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
Exclusion criteria
Exclusion criteria: 1. Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 28 days after the final dose of study drug 2. Treatment with investigational therapy (or blinded comparator) within 90 days or 5 drug elimination half-lives, whichever is longer, prior to initiation of study drug 3. Treatment with any immunosuppressive medication within 28 days or 5 drug elimination half-lives, whichever is longer, prior to initiation of study drug 4. Treatment with an herbal or homoeopathic remedy within 14 days or 5 drug elimination half-lives (whichever is longer) prior to initiation of study drug 5. Treatment with any vaccine within 14 days prior to initiation of study drug or a scheduled vaccination during study period (through the follow-up/early termination visit) 6. Positive for tuberculosis (TB) during screening or within 3 months prior to screening, defined as a positive QuantiFERON®-TB Gold test (QFT) 7. Positive human immunodeficiency virus (HIV) test at screening 8. Positive hepatitis B surface antigen (HBsAg) test at screening 9. Positive hepatitis C virus (HCV) antibody test at screening 10. Receipt of blood products within 120 days prior to screening 11. Hospitalisation within 28 days prior to initiation of study drug 12. Anticipation of need for a surgical procedure during the study 13. Infection requiring oral or intravenous (IV) antibiotics within 28 days prior to screening or any evidence of current infection (e.g., bacterial, viral, fungal) 14. Upper or lower respiratory tract infection within 2 weeks prior to initiation of study drug 15. Documented physician-diagnosed asthma for at least 12 months prior to screening 16. Post-bronchodilator reversibility of FEV1 (litres) =12% and =200 mL at screening 17. Any medical condition or abnormal clinical laboratory finding that, in the investigator's judgement, would preclude the participant's safe participation in and completion of the study or could affect the interpretation of the results 18. History of malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer 19. History of any significant drug or food allergy (e.g., allergic reactions that resulted in anaphylaxis or hepatotoxicity) 20. History of symptomatic bradycardia 21. History of ataxia or condition associated with ataxia 22. Abnormally low total lung capacity, defined as <80% of predicted for participants of European descent or <75% of predicted for participants of non-European descent, at screening 23. Diffusion capacity of the lung for carbon monoxide, defined as <75% of predicted for participants of European descent or <70% of predicted for participants of non-European descent, at screening 24. Glomerular filtration rate <80 millilitres per minute (mL/min)/1.73 square metre (m^2) as calculated through use of the Chronic Kidney Disease Epidemiology Collaboration equation. Participants with a glomerular filtration rate =80 mL/min/1.73 m² and <90 mL/min/1.73 m² are eligible only if have confirmed cystatin C value below upper limit of normal (ULN)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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) | — |
Countries
England, United Kingdom
Contacts
Public ContactNand Singh
Outcome results
None listed