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

NCT01772290 | Completed Phase 1

• 1 other identifier: GP28465
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 2

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.

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (4)

A: Vismodegib

ACTIVE COMPARATOR

Drug: vismodegib

B: Rabeprazole + Vismodegib

EXPERIMENTAL

Drug: rabeprazole; Drug: vismodegib

C: Itraconazole + Vismodegib

EXPERIMENTAL

Drug: itraconazole; Drug: vismodegib

D: Fluconazole + Vismodegib

EXPERIMENTAL

Drug: fluconazole; Drug: vismodegib

Interventions

fluconazole DRUG

Multiple oral doses

D: Fluconazole + Vismodegib

itraconazole DRUG

Multiple oral doses

C: Itraconazole + Vismodegib

rabeprazole DRUG

Multiple oral doses

B: Rabeprazole + Vismodegib

vismodegib DRUG

Multiple oral doses

A: Vismodegib; B: Rabeprazole + Vismodegib; C: Itraconazole + Vismodegib; D: Fluconazole + Vismodegib

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (2)

Unknown Facility

Daytona Beach, Florida, 32117, United States

Location

Unknown Facility

Dallas, Texas, 75247, United States

Location

Related Publications (1)

• Malhi V, Colburn D, Williams SJ, Hop CE, Dresser MJ, Chandra P, Graham RA. A clinical drug-drug interaction study to evaluate the effect of a proton-pump inhibitor, a combined P-glycoprotein/cytochrome 450 enzyme (CYP)3A4 inhibitor, and a CYP2C9 inhibitor on the pharmacokinetics of vismodegib. Cancer Chemother Pharmacol. 2016 Jul;78(1):41-9. doi: 10.1007/s00280-016-3020-z. Epub 2016 May 6.

  PMID: 27154174 DERIVED

MeSH Terms

Interventions

Fluconazole; Itraconazole; Rabeprazole; HhAntag691

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2013
• First Posted: January 21, 2013
• Study Start: February 1, 2013
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: November 2, 2016

Record last verified: 2016-11

Locations

US (2)