A Drug-Drug Interaction Study Between GDC-0853 and Midazolam, Itraconazole, Rosuvastatin, and Simvastatin

Study Overview
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Brief Summary
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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
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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.

Official Title
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A 4-Part Phase 1 Study to Evaluate the Effect of GDC-0853 on the Pharmacokinetics of Midazolam, Rosuvastatin, and Simvastatin and the Effect of Itraconazole on the Pharmacokinetics of GDC-0853

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: Midazolam
* Drug: GDC-0853
* Drug: Midazolam and GDC-0853
* Drug: Rosuvastatin
* Drug: Rosuvastatin and GDC-0853
* Drug: Simvastatin
* Drug: Simvastatin and GDC-0853
* Drug: GDC-0853
* Drug: Itraconazole
* Drug: GDC-0853 and itraconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1<br>Participants will receive a single dose of midazolam followed by multiple doses of GDC-0853 coadministered with a single dose of midazolam. | Drug: Midazolam<br>* Single dose midazolam<br>Drug: GDC-0853<br>* Multiple doses GDC-0853 for 6 days<br>Drug: Midazolam and GDC-0853<br>* Multiple doses GDC-0853 and single dose midazolam<br>|
| Experimental: Part 2<br>Participants will receive a single dose of rosuvastatin followed by multiple doses of GDC-0853 coadministered with a single dose of rosuvastatin. | Drug: GDC-0853<br>* Multiple doses GDC-0853 for 6 days<br>Drug: Rosuvastatin<br>* Single dose rosuvastatin<br>Drug: Rosuvastatin and GDC-0853<br>* Multiple doses GDC-0853 and single dose rosuvastatin<br>|
| Experimental: Part 3<br>Participants will receive a single dose of simvastatin followed by multiple doses of GDC-0853 coadministered with a single dose of simvastatin. | Drug: GDC-0853<br>* Multiple doses GDC-0853 for 6 days<br>Drug: Simvastatin<br>* Single dose simvastatin<br>Drug: Simvastatin and GDC-0853<br>* Multiple doses GDC-0853 and single dose simvastatin<br>|
| Experimental: Part 4<br>Participants will receive a single dose of GDC-0853 followed by multiple doses of itraconazole coadministered with a single dose of GDC-0853. | Drug: GDC-0853<br>* Single dose GDC-0853<br>Drug: Itraconazole<br>* Multiple doses itraconazole for 6 days<br>Drug: GDC-0853 and itraconazole<br>* Multiple doses itraconazole and single dose GDC-0853<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to approximately 7 weeks | 
| Cmax | 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. | 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. | 0.5 up to 12 hours post-dose on Days 11 and 12 |