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

Sponsor

Genentech, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT03174041

Collaborator

(none)

Enrollment

Locations

Arms

2.2

Actual Duration (Months)

Patients Per Site

9.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Participants	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	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

63 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Apr 18, 2017

Actual Primary Completion Date :

Jun 23, 2017

Actual Study Completion Date :

Jun 23, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Covance Research Unit - Daytona	Daytona Beach	Florida	United States	32117
2	Covance Clinical Research Unit Inc.; Covance Gfi Research	Evansville	Indiana	United States	47710
3	Covance Clinical Research Unit, Inc	Madison	Wisconsin	United States	53704

Sponsors and Collaborators

Genentech, Inc.

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Genentech, Inc.

ClinicalTrials.gov Identifier:

NCT03174041

Other Study ID Numbers:

GP39616

First Posted:

Jun 2, 2017

Last Update Posted:

Sep 24, 2019

Last Verified:

Sep 1, 2019

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Study Results

No Results Posted as of Sep 24, 2019