A Drug-Drug Interaction Study of the Effect of Rabeprazole, Itraconazole or Fluconazole on the Pharmacokinetics of Vismodegib

Healthy Volunteer Clinical Trial

Official title:

A Clinical Drug-Drug Interaction Study to Evaluate the Effect of a Proton Pump Inhibitor, a Combined P-gp/CYP3A4 Inhibitor, and a CYP2C9 Inhibitor on the Pharmacokinetics of Vismodegib

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01772290
• Other study ID #: GP28465
• Status: Completed
• Phase: Phase 1
• First received: January 17, 2013
• Last updated: November 1, 2016
• Start date: February 2013
• Est. completion date: May 2013

Study information

• Verified date: November 2016
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Drug:
• fluconazole
Multiple oral doses
• itraconazole
Multiple oral doses
• rabeprazole
Multiple oral doses
• vismodegib
Multiple oral doses

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No