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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech
ClinicalTrials.gov Identifier:
NCT01772290
First received: January 17, 2013
Last updated: August 4, 2014
Last verified: August 2014
  Purpose

This randomized, open-label, 4-arm, multiple-dose study will evaluate the effec t of coadministration of a protein pump inhibitor, an inhibitor of P-glycoprotei n and CYP3A4, or an inhibitor of CYP2C9 on the pharmacokinetics of vismodegib i n healthy female subjects of non-childbearing potential. Subjects will be random ized to receive multiple oral doses of vismodegib, alone or in combination with multiple oral doses of either rabeprazole, itraconazole or fluconazole. Anticipa ted time on study treatment is up to 11 days.


Condition Intervention Phase
Healthy Volunteer
Drug: vismodegib
Drug: rabeprazole
Drug: itraconazole
Drug: fluconazole
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by Genentech:

Primary Outcome Measures:
  • Relative effect of rabeprazole on steady-state pharmacokinetics of vismodegib: Area under the concentration-time curve (AUC)/Steady-state concentration (Css) [ Time Frame: up to 12 days ] [ Designated as safety issue: No ]
  • Relative effect of itraconazole on steady-state pharmacokinetics of vismodegib: Area under the concentration-time curve (AUC)/Steady-state concentration (Css) [ Time Frame: up to 12 days ] [ Designated as safety issue: No ]
  • Relative effect of fluconazole on the steady-state pharmacokinetics of vismodegib: Area under the concentration-time curve (AUC)/Steady-state concentration (Css) [ Time Frame: up to 12 days ] [ Designated as safety issue: No ]

Enrollment: 92
Study Start Date: February 2013
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A: Vismodegib Drug: vismodegib
Multiple oral doses
Experimental: B: Rabeprazole + Vismodegib Drug: vismodegib
Multiple oral doses
Drug: rabeprazole
Multiple oral doses
Experimental: C: Itraconazole + Vismodegib Drug: vismodegib
Multiple oral doses
Drug: itraconazole
Multiple oral doses
Experimental: D: Fluconazole + Vismodegib Drug: vismodegib
Multiple oral doses
Drug: fluconazole
Multiple oral doses

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01772290

Locations
United States, Florida
Daytona Beach, Florida, United States, 32117
United States, Texas
Dallas, Texas, United States, 75247
Sponsors and Collaborators
Genentech
Investigators
Study Director: Clinical Trials Genentech
  More Information

No publications provided

Responsible Party: Genentech
ClinicalTrials.gov Identifier: NCT01772290     History of Changes
Other Study ID Numbers: GP28465
Study First Received: January 17, 2013
Last Updated: August 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Fluconazole
Itraconazole
Hydroxyitraconazole
Rabeprazole
Proton Pump Inhibitors
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Ulcer Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on August 21, 2014