A Drug-Drug Interaction Study Between GDC-0853 and Midazolam, Itraconazole, Rosuvastatin, and Simvastatin
- Conditions
- Healthy Participants
- Interventions
- Registration Number
- NCT03174041
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
The purpose of this study is to assess the potential for a drug interaction between GDC-0853 and midazolam, itraconazole, rosuvastatin, and simvastatin.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 63
- Within body mass index range of 18 to 31 kilograms per square meter, inclusive
- Females will be non-pregnant, non-lactating, and either postmenopausal or surgically sterile
- Males will either be sterile or agree to use an approved method of contraception
- Significant history or clinical manifestation of any significant metabolic, allergic/immunologic/immunodeficiency, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder (as determined by the investigator)
- History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator
- Participation in any other investigational study drug trial in which receipt of any investigational study drug occurred within 30 days or 5 half-lives, whichever is longer, prior to check in
- History of malignancy, except for appropriately treated carcinoma in situ of the cervix or non-melanoma skin carcinoma with 3-year disease-free follow up
- Any acute or chronic condition or any other reason that, in the opinion of the investigator, would limit the participant's ability to complete and/or participate in this clinical study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 3 Simvastatin and GDC-0853 Participants will receive a single dose of simvastatin followed by multiple doses of GDC-0853 coadministered with a single dose of simvastatin. Part 1 Midazolam and GDC-0853 Participants will receive a single dose of midazolam followed by multiple doses of GDC-0853 coadministered with a single dose of midazolam. Part 4 GDC-0853 and itraconazole Participants will receive a single dose of GDC-0853 followed by multiple doses of itraconazole coadministered with a single dose of GDC-0853. Part 4 GDC-0853 Participants will receive a single dose of GDC-0853 followed by multiple doses of itraconazole coadministered with a single dose of GDC-0853. Part 2 GDC-0853 Participants will receive a single dose of rosuvastatin followed by multiple doses of GDC-0853 coadministered with a single dose of rosuvastatin. Part 1 GDC-0853 Participants will receive a single dose of midazolam followed by multiple doses of GDC-0853 coadministered with a single dose of midazolam. Part 2 Rosuvastatin and GDC-0853 Participants will receive a single dose of rosuvastatin followed by multiple doses of GDC-0853 coadministered with a single dose of rosuvastatin. Part 3 GDC-0853 Participants will receive a single dose of simvastatin followed by multiple doses of GDC-0853 coadministered with a single dose of simvastatin. Part 1 Midazolam Participants will receive a single dose of midazolam followed by multiple doses of GDC-0853 coadministered with a single dose of midazolam. Part 2 Rosuvastatin Participants will receive a single dose of rosuvastatin followed by multiple doses of GDC-0853 coadministered with a single dose of rosuvastatin. Part 3 Simvastatin Participants will receive a single dose of simvastatin followed by multiple doses of GDC-0853 coadministered with a single dose of simvastatin. Part 4 Itraconazole Participants will receive a single dose of GDC-0853 followed by multiple doses of itraconazole coadministered with a single dose of GDC-0853.
- Primary Outcome Measures
Name Time Method Maximum Observed Concentration (Cmax) 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 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.
Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) 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 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants with Adverse Events (AEs) and AEs of Special Interest (AESIs) Up to approximately 7 weeks 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.
Cmax 0.5 up to 12 hours post-dose on Days 11 and 12 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.
AUC0-12 0.5 up to 12 hours post-dose on Days 11 and 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.
Trial Locations
- Locations (3)
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