Clinical trial NCT01940510: A Study of the Effect of Multiple Doses of Rifampin on the Single Dose Pharmacokinetics of RO5424802
Official title: An Open-Label, Three-Period, Fixed Sequence Study to Investigate the Effect of Multiple Oral Doses of Rifampin, a Potent Cytochrome P450 3A Inducer, on the Single Dose Pharmacokinetics of RO5424802 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-09-12
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

Brief summary: This single center, open-label, 3-period, fixed-sequence study will evaluate the effect of multiple oral doses of rifampin on the pharmacokinetics of a single oral dose of RO5424802 in healthy volunteers. Subjects will receive a single dose of RO5424802 on Days 1 and 17 and rifampin daily from Days 8 to Day 20.


Eligibility criteria: Inclusion Criteria:

* Healthy male and female volunteers, 18 to 55 years of age inclusive. Healthy status will be defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, and a complete physical examination
* Body mass index (BMI) between 18 to 32 kg/m2 inclusive
* Nonsmoking subjects and former smoking subjects (who have not smoked for the past six months before first dosing)
* Female subjects must be surgically sterile or postmenopausal for the past year
* Male subjects and their partners of childbearing potential must be willing to use two effective methods of contraception, one of which must be a barrier method (e.g., condom) during the study and for 90 days after the last drug administration

Exclusion Criteria:

* Women of childbearing potential, pregnant or lactating women, or males with female partners who are pregnant or lactating
* Positive urine test for drugs of abuse, alcohol, or cotinine test at screening or prior to admission to the study unit
* Suspicion of regular consumption of drug(s) of abuse including marijuana
* Current smokers or subjects who have discontinued smoking less than six months prior to first dosing
* History (within three months of Screening) of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol). Alcohol consumption will be prohibited 72 hours prior to entry in the clinical site center and throughout the entire study (including the washout period) until discharge
* Positive for hepatitis B, hepatitis C, or HIV infection
* Participation in an investigational drug or device study within 45 days or 5 half-lives (whichever time period is longer) or 6 months for biologic therapies prior to first dosing
* Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, absorption, distribution, metabolism or excretion of study medication, or that would, in the opinion of the PI, pose an unacceptable risk to the subject in this study
* History of hypersensitivity to any of the additives in the RO5424802 formulation (lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, hydroxypropyl cellulose, sodium lauryl sulphate, magnesium stearate)
* Any history of hypersensitivity to or contraindication to the use of rifampin or other rifamycins or history of severe drug-related allergic reactions or hepatoxicity

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Alectinib
timeFrame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
measure: Maximum Observed Plasma Concentration (Cmax) of Alectinib
timeFrame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Secondary outcomes:
measure: AUC(0-inf) of RO5468924
timeFrame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
measure: Cmax of RO5468924
timeFrame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
measure: Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for AUC(0-inf)
timeFrame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
measure: Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for Cmax
timeFrame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of Alectinib and RO5468924
timeFrame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib and RO5468924
timeFrame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
measure: Plasma Terminal Half-Life (t1/2) of Alectinib and RO5468924
timeFrame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
measure: Apparent Oral Clearance (CL/F) of Alectinib
timeFrame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
measure: Apparent Volume of Distribution (Vz/F) of Alectinib
timeFrame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
measure: Total Molar Concentration of Alectinib and RO5468924 as Derived by AUC(0-inf)
timeFrame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
measure: Total Molar Concentration of Alectinib and RO5468924 as Derived by Cmax
timeFrame: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Other outcomes:
Locations:
city: Austin
country: United States
state: Texas
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: