A Study of the Effect of Multiple Doses of Rifampin on the Single Dose Pharmacokinetics of RO5424802

NCT01940510 | Completed Phase 1 Results

• 1 other identifier: NP29042
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (2)

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

  AUC(0-inf) is the area under the alectinib plasma concentration versus time curve (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 nanogram times (\*) hour per milliliter (ng\*hour/mL).

  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

• Maximum Observed Plasma Concentration (Cmax) of Alectinib

  Cmax is the maximum observed alectinib plasma concentration, presented in nanogram per milliliter (ng/mL).

  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 (11)

• AUC(0-inf) of RO5468924

  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

• Cmax of RO5468924

  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

• Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for AUC(0-inf)

  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

• Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for Cmax

  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

• Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of Alectinib and RO5468924

  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

Study Arms (1)

Healthy subjects

EXPERIMENTAL

Drug: RO5424802; Drug: rifampin

Interventions

RO5424802 DRUG

Single dose without (Day 1) and with (Day 17) co-administration of rifampin

Healthy subjects

rifampin DRUG

Multiple doses Days 8-16 and Days 17-20

Healthy subjects

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (1)

Unknown Facility

Austin, Texas, 78744, United States

Location

MeSH Terms

Interventions

alectinib; Rifampin

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: September 9, 2013
• First Posted: September 12, 2013
• Study Start: October 1, 2013
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: December 21, 2016
• Results First Posted: October 18, 2016

Record last verified: 2016-11

Locations

US (1)