Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Anti-Infective Agents

All Drugs and Chemicals

Antineoplastic Agents

Rifampin

Vemurafenib

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Enzyme Inhibitors

Protein Kinase Inhibitors

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).

Rifampin at a dose of 600 mg as capsules orally once daily will be administered from Days 8 through 23 (Periods B and C).

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).

Clinical Trials

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).

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

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

Tmax is the time from vemurafenib administration to reach Cmax for vemurafenib.

Plasma elimination half-life is the time measured during drug elimination phase for the plasma drug concentration to decrease by one half.

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.

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.

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).

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).

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.

Cmax is the maximum observed plasma vemurafenib concentration, presented in microgram per milliliter (mcg/mL).

Hoffmann-La Roche

The safety analysis population included all participants who received at least 1 dose of vemurafenib.

Participants, after an overnight fast of at least 10 hours, received vemurafenib alone at a dose of 960 mg as film-coated tablets orally on Day 1.

Vemurafenib (Intervention Period A)

Participants received rifampin alone at a dose of 600 mg as capsules orally once daily from Days 8 through 16.

Rifampin (Intervention Period B)

Participants, after an overnight fast of at least 10 hours, received vemurafenib at a dose of 960 mg as film-coated tablets orally with rifampin at a dose of 600 mg as capsules orally on Day 17 and rifampin alone at a dose of 600 mg as capsules orally once daily was administered from Days 18 through 23.

Vemurafenib + Rifampin (Intervention Period C)

There were 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, received vemurafenib at a dose of 960 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 was administered from Days 8 through 16 (Period B) and from Days 18 through 23 (Period C).

Vemurafenib + Rifampin (All Periods)

Age, Continuous

Sex: Female, Male

The intent-to-treat (ITT) population included all participants who were enrolled in the study.

Medical Communications

Analysis of variance (ANOVA) was applied to the log-transformed PK parameters, and then back transformed to provide geometric mean ratio (Period C/Period A) and confidence intervals.

Participants, after an overnight fast of at least 10 hours, received vemurafenib at a dose of 960 mg as film-coated tablets orally along with rifampin at a dose of 600 mg as capsules orally on Day 17 and rifampin alone at a dose of 600 mg as capsules orally once daily was administered from Days 18 through 23.

The pharmacokinetics (PK) parameter population included all participants who received both scheduled doses of vemurafenib and who provided adequate PK assessments to calculate important PK parameters.

Area Under the Plasma Concentration Time-curve From Zero to the Last Measurable Concentration Time Point (AUClast) of Vemurafenib

ANOVA was applied to the log-transformed PK parameters, and then back transformed to provide geometric mean ratio (Period C/Period A) and confidence intervals.

Area Under the Plasma Concentration Time-curve From Zero to Extrapolated Infinite Time (AUC[0-inf]) of Vemurafenib

Maximum Observed Plasma Concentration (Cmax) of Vemurafenib

Time to Reach Cmax (Tmax) of Vemurafenib

Plasma Elimination Half Life (t1/2) of Vemurafenib

Plasma Apparent Clearance (CL/F) of Vemurafenib

Area Under the Plasma Concentration Time-curve From Zero to 168 Hours [AUC(0-168)] of Vemurafenib

Percent Extrapolated AUC(0-inf) (AUCpeo) of Vemurafenib

There were 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, received vemurafenib (Zelboraf) 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 was administered from Days 8 through 16 (Period B) and from Days 18 through 23 (Period C).

Spots Global Cancer Trial Database for A Pharmacokinetics (PK) Study to Investigate the Effect of Rifampin on PK of Vemurafenib (Zelboraf)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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