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A Pharmacokinetics (PK) Study to Investigate the Effect of Rifampin on PK of Vemurafenib (Zelboraf)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01765543
First received: January 9, 2013
Last updated: October 21, 2016
Last verified: October 2016
  Purpose
This open-label, multi-center, three-period, one-sequence study will investigate the effect of rifampin on the PK of vemurafenib in participants with unresectable BRAFV600-mutation positive metastatic melanoma or other malignant tumor type that harbors a V600-activating mutation of BRAF without acceptable standard treatment options. Eligible participants will have the option to continue treatment with vemurafenib as part of an extension study GO28399 (NCT01739764).

Condition Intervention Phase
Malignant Melanoma, Neoplasms
Drug: Rifampin
Drug: Vemurafenib
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label, Multicenter, Three-Period, One-Sequence Study to Investigate the Effect of Rifampin on the Pharmacokinetics of a Single Oral Dose of 960 mg of Vemurafenib

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Area Under the Plasma Concentration Time-curve From Zero to the Last Measurable Concentration Time Point (AUClast) of Vemurafenib [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C) ]
    AUClast is the area under the vemurafenib plasma concentration versus time curve from time zero to the time of last measured concentration of vemurafenib (Tlast). Area under the curve (AUC) is a measure of the plasma concentration of a drug over time. AUClast is presented in micrograms times (*) hour per milliliter (mcg*h/mL).

  • Area Under the Plasma Concentration Time-curve From Zero to Extrapolated Infinite Time (AUC[0-inf]) of Vemurafenib [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C) ]
    AUC(0-inf) is the AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of a drug over time. AUC(0-inf) is presented in mcg*h/mL.

  • Maximum Observed Plasma Concentration (Cmax) of Vemurafenib [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C) ]
    Cmax is the maximum observed plasma vemurafenib concentration, presented in microgram per milliliter (mcg/mL).


Other Outcome Measures:
  • Time to Reach Cmax (Tmax) of Vemurafenib [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C) ]
    Tmax is the time from vemurafenib administration to reach Cmax for vemurafenib.

  • Plasma Elimination Half Life (t1/2) of Vemurafenib [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C) ]
    Plasma elimination half-life is the time measured during drug elimination phase for the plasma drug concentration to decrease by one half.

  • Plasma Apparent Clearance (CL/F) of Vemurafenib [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C) ]
    Clearance of a drug is a measure of the rate at which a drug is removed (metabolized or eliminated by normal biological processes) from the blood. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.

  • Area Under the Plasma Concentration Time-curve From Zero to 168 Hours [AUC(0-168)] of Vemurafenib [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C) ]
    AUC(0-168) is the AUC from time zero (pre-dose) to 168 hours (time point for last blood sample collection). AUC is a measure of the plasma concentration of a drug over time. AUC(0-168) is presented in mcg*h/mL.

  • Percent Extrapolated AUC(0-inf) (AUCpeo) of Vemurafenib [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C) ]
    The AUCpeo, that is, percent area obtained after extrapolation from Tlast to infinity is calculated by using the formula AUCpeo = 100*(AUC[0-inf] minus AUC[0-last])/AUC(0-inf). This parameter provides information about what percentage of the theoretical curve AUC(0-inf) is possible to determine experimentally (AUC0-last).


Enrollment: 27
Study Start Date: July 2013
Study Completion Date: November 2015
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vemurafenib + Rifampin
There will be 3 intervention periods in the study: Period A (Days 1 to 7), Period B (Days 8 to 16), and Period C (Days 17 to 24). Participants, after an overnight fast of at least 10 hours, will receive vemurafenib at a dose of 960 milligrams (mg) as film-coated tablets orally alone on Day 1 (Period A); with rifampin (at a dose of 600 mg as capsules orally) on Day 17 (Period C); and rifampin alone at a dose of 600 mg as capsules orally once daily will be administered from Days 8 through 16 (Period B) and from Days 18 through 23 (Period C).
Drug: Rifampin
Rifampin at a dose of 600 mg as capsules orally once daily will be administered from Days 8 through 23 (Periods B and C).
Drug: Vemurafenib
Participants, after an overnight fast of at least 10 hours, will receive vemurafenib at a dose of 960 mg as film-coated tablets orally on Day 1 (Period A) and on Day 17 (Period C).
Other Name: RO5185426, Zelboraf

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants with either unresectable Stage IIIc or Stage IV metastatic melanoma positive for the BRAF V600 mutation or other malignant tumor type that harbors a V600-activating mutation of BRAF, as determined by results of cobas® 4800 BRAF V600 mutation test or a Deoxyribonucleic acid (DNA) sequencing method, and who have no acceptable standard treatment options
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  • Life expectancy of greater than or equal to (>/=) 12 weeks
  • Full recovery from the effects of any major surgery or significant traumatic injury within 14 days prior to the first dose of study treatment
  • Adequate hematologic and end organ function
  • Female participants of childbearing potential and male participants with partners of childbearing potential must agree to always use 2 effective methods of contraception
  • Negative serum pregnancy test within 7 days prior to commencement of dosing in women of childbearing potential

Exclusion Criteria:

  • Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of first dose of study drug
  • Requirement for immediate or urgent treatment with daily vemurafenib and for whom the intermittent schedule of vemurafenib employed during the 24-day period for this trial is not clinically acceptable
  • Allergy or hypersensitivity to components of the vemurafenib formulation
  • Experimental therapy within 4 weeks prior to first dose of study drug
  • Major surgical procedure or significant traumatic injury within 14 days prior to first dose of study drug, or anticipation of the need for major surgery during study treatment
  • Prior anti-cancer therapy within 28 days before the first dose of study drug
  • History of clinically significant cardiac or pulmonary dysfunction
  • History of symptomatic congestive heart failure of any New York Heart Association class or serious cardiac arrhythmia requiring treatment
  • History of myocardial infarction within 6 months prior to first dose of study drug
  • Current dyspnea at rest, owing to complications of advanced malignancy or any requirement for supplemental oxygen to perform activities of daily living
  • History of congenital long QT syndrome or corrected QT interval (QTc) greater than (>) 450 milliseconds
  • Active central nervous system lesions
  • Uncontrolled or poorly controlled diabetes
  • Current severe, uncontrolled systemic disease
  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: NCT01765543

Locations
United States, Arkansas
Rogers, Arkansas, United States, 72758
United States, California
Pleasant Hill, California, United States, 94523
United States, Ohio
Middletown, Ohio, United States, 45042
United States, Texas
Dallas, Texas, United States, 75246
Brazil
Porto Alegre, RS, Brazil, 90020-090
Porto Alegre, RS, Brazil, 90035-003
Porto Alegre, RS, Brazil, 90840-440
Croatia
Varazdin, Croatia, 42000
Zagreb, Croatia, 10000
Egypt
Alexandria, Egypt, 21131
Cairo, Egypt, 11796
Dakahlia, Egypt, 324
Tanta, Egypt
South Africa
Cape Town, South Africa, 7570
Port Elizabeth, South Africa, 6045
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01765543     History of Changes
Other Study ID Numbers: GO28052  2012-003142-33 
Study First Received: January 9, 2013
Results First Received: October 21, 2016
Last Updated: October 21, 2016

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Rifampin
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers

ClinicalTrials.gov processed this record on February 23, 2017