The purpose of this study is to assess the potential for a drug interaction between GDC-0853 and midazolam, itraconazole, rosuvastatin, and simvastatin.
This will be a 4-part study, with each part being an open-label fixed-sequence evaluation conducted in healthy adult participants. Approximately 64 participants will be enrolled in this study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
63
Covance Research Unit - Daytona
Daytona Beach, Florida, United States
Covance Clinical Research Unit Inc.; Covance Gfi Research
Evansville, Indiana, United States
Covance Clinical Research Unit, Inc
Madison, Wisconsin, United States
Maximum Observed Concentration (Cmax)
Cmax for midazolam (Part 1), rosuvastatin (Part 2), and simvastatin (Part 3) in the presence and absence of GDC-0853 and Cmax for GDC-0853 (Part 4) in the presence and absence of itraconazole.
Time frame: Part 1: Pre-dose, 0.5 up to 48 hours post-dose Days 1, 9. Part 2: pre-dose, 0.5 up to 96 hours post-dose Days 1, 12. Part 3: pre-dose, 0.5 up to 48 hours post-dose on Days 1, 9. Part 4: pre-dose, 0.5 up to 48 hours post-dose Days 1, 10
Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t)
AUC0-t for midazolam (Part 1), rosuvastatin (Part 2), and simvastatin (Part 3) in the presence and absence of GDC-0853 and AUC0-t for GDC-0853 (Part 4) in the presence and absence of itraconazole.
Time frame: Part 1: Pre-dose, 0.5 up to 48 hours post-dose Days 1, 9. Part 2: pre-dose, 0.5 up to 96 hours post-dose Days 1, 12. Part 3: pre-dose, 0.5 up to 48 hours post-dose on Days 1, 9. Part 4: pre-dose, 0.5 up to 48 hours post-dose Days 1, 10
Percentage of Participants with Adverse Events (AEs) and AEs of Special Interest (AESIs)
An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. AESIs include any serious infection, any infections requiring intravenous antimicrobials, and any opportunistic infections; bleeding events of moderate or greater severity; a laboratory result of aspartate aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>5 × upper limit of normal (ULN) or an AST or ALT \> 3 × ULN in combination with a total bilirubin \> 2 × ULN, of which at least 35% is direct bilirubin or there is clinical jaundice; cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's law; or suspected transmission of an infectious agent by the study drug.
Time frame: Up to approximately 7 weeks
Cmax
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Single dose rosuvastatin
Multiple doses GDC-0853 and single dose rosuvastatin
Single dose simvastatin
Multiple doses GDC-0853 and single dose simvastatin
Single dose GDC-0853
Multiple doses itraconazole for 6 days
Multiple doses itraconazole and single dose GDC-0853
Cmax for GDC-0853 (Parts 2 and 3) in the presence and absence of rosuvastatin and simvastatin, respectively, and Cmax for itraconazole (Part 4) in the presence and absence of GDC-0853.
Time frame: 0.5 up to 12 hours post-dose on Days 11 and 12
AUC0-12
AUC0-12 for GDC-0853 (Parts 2 and 3) in the presence and absence of rosuvastatin and simvastatin, respectively, and AUC0-12 for itraconazole (Part 4) in the presence and absence of GDC-0853.
Time frame: 0.5 up to 12 hours post-dose on Days 11 and 12