Healthy Volunteer
Conditions
Brief summary
This randomized, open-label, 4-arm, multiple-dose study will evaluate the effect of coadministration of a protein pump inhibitor, an inhibitor of P-glycoprotein and CYP3A4, or an inhibitor of CYP2C9 on the pharmacokinetics of vismodegib in healthy female subjects of non-childbearing potential. Subjects will be randomized to receive multiple oral doses of vismodegib, alone or in combination with multiple oral doses of either rabeprazole, itraconazole or fluconazole. Anticipated time on study treatment is up to 11 days.
Interventions
DRUGfluconazole
Multiple oral doses
DRUGitraconazole
Multiple oral doses
DRUGrabeprazole
Multiple oral doses
DRUGvismodegib
Multiple oral doses
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Females of non-childbearing potential * Body mass index (BMI) 18 to 32 kg/m2, inclusive * In good health, determined by no clinically significant findings from medical history, physical examination. 12-lead ECG, and vital signs * Clinical laboratory evaluations, complete blood count and urinalysis within the normal range for the test laboratory, unless not deemed clinically significant by the investigator * Negative test for drugs of abuse at screening and check-in (including alcohol) * Negative for hepatitis B, hepatitis C and HIV infection * Non-childbearing potential is defined as: non-pregnant, non-lactating, and either postmenopausal for at least 1 year or surgically sterile (e.g. bilateral oophorectomy and/or hysterectomy)
Exclusion criteria
* Significant history or clinical evidence of any metabolic (including type 1 or 2 diabetes). allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, endocrine, GI (including gastric or duodenal ulcers), Zollinger-Ellison syndrome, Barrett's esophagus, urological, neurological, or psychiatric disorder * History of inflammatory arthritis * History of symptomatic hypotension * History of seizure disorders * History of bipolar or major depressive disorder * History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (appendectomy, hernia repair, and/or cholecystectomy will be allowed) * History of alcoholism or drug addiction within 1 year prior to check-in * Use of any tobacco- or nicotine-containing products within 6 months prior to check-in * Participation in any other investigational study drug or biological agent trial in which receipt of investigational study drug occurred within 5 half-lives or 30 days, whichever is longer, prior to check-in * Use of PPIs, H2-receptor antagonists, or antacids within 1 month prior to check-in * History of chronic PPI use (\> 30 days of continuous daily dosing) within 6 months of check-in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Relative effect of rabeprazole on steady-state pharmacokinetics of vismodegib: Area under the concentration-time curve (AUC)/Steady-state concentration (Css) | up to 12 days |
| Relative effect of itraconazole on steady-state pharmacokinetics of vismodegib: Area under the concentration-time curve (AUC)/Steady-state concentration (Css) | up to 12 days |
| Relative effect of fluconazole on the steady-state pharmacokinetics of vismodegib: Area under the concentration-time curve (AUC)/Steady-state concentration (Css) | up to 12 days |
Countries
United States
Outcome results
None listed