Clinical trial NCT02074553: A Cross-over Study Examining the Bioequivalence of 3 Test Formulations to a Reference Formulation of Alectinib (RO5424802) in Healthy Volunteers
Official title: A Randomized, Open-Label, Single Dose, Cross-Over Study to Investigate the Bioequivalence of Three RO5424802 Test Formulations Versus a Reference Formulation Following Oral Administration in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2014-02-28
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This 2-part, single center, open-label, randomized, single-dose, 4-sequence, 4-period cross-over study will compare the bioequivalence of three test RO5424802 capsule formulations with the reference capsule formulation in healthy adult volunteers. All participants in both fasted (Part 1) and fed (Part 2) conditions of the study will receive each of 4 treatments (Ro542-4802/F03 \[RO5424802 with 50 percentage (%) sodium lauryl sulfate (SLS) (reference)\], Ro542-4802/F07 \[RO5424802 with 25% SLS (test)\], Ro542-4802/F14 \[RO5424802 with 12.5% SLS (test)\] and Ro542-4802/F08 \[RO5424802 with 3% SLS (test)\] in a randomized sequence. Each treatment will be given as a single 600 milligrams (mg) oral administration in an upright position on Day 1 after an overnight fast, followed by a 10-day washout period. Total time on study is expected to last up to 75 days, for each enrolled participant.


Eligibility criteria: Inclusion Criteria:

* Healthy male and surgically sterile or post-menopausal female participants 18-55 years of age
* Body mass index (BMI) between 18 to 32 kilograms per meter-squared (kg/m\^2)
* Non-smoking participants and former smoking participants (who have not smoked for the past six months before first dosing)
* Male participants and their partners of child-bearing potential must be willing to use two effective contraceptive methods as defined by protocol
* Willing to abstain from xanthine-containing beverages and food (coffee, tea, cola, chocolate, and "energy drinks") from 72 hours prior to Day -1 through the study
* Willing to abstain from grapefruit, pomelo, star fruit or Seville orange containing products from day 7 prior study start until study end
* Willing to avoid prolonged sun exposure while taking RO5424802 and through follow-up

Exclusion Criteria:

* Pregnant or lactating women, men with female partners who are pregnant or lactating, or women of child bearing potential
* Clinically significant abnormalities on physical examination, vital signs, or laboratory test results during screening or prior to admission to the study unit
* Positive test for drugs of abuse, alcohol or cotinine test at screening or prior to admission to the study unit or suspicion of regular consumption of drug(s) of abuse
* History of recent alcohol consumption exceeding 2 standard drinks per day on average. Alcohol consuming is prohibited from 72 hours prior to study start until the end of the study
* Participants with any risk factors or family history for QT/QTcF and electrocardiogram (ECG) abnormalities
* A history of any concurrent clinically significant hematologic, renal, hepatic, pulmonary, neurological, psychiatric, allergies, gastrointestinal, metabolic or endocrine disorder, or cardiovascular disease or infections
* Positive screening test for hepatitis B, C, or human immunodeficiency virus (HIV)
* Use of any medications (prescriptions or over-the-counter), within 2 weeks or 5 half-lives (whichever is longer) before the first dose of study medication with exception of acetaminophen up to 2 grams (g) per day up to 48 hours prior to dosing, not to exceed 4 g total during the week prior to dosing
* Routine or chronic use of more than 2 g of acetaminophen daily
* Use of any herbal supplements (for example, St. John's Wort) or any metabolic inducers within 4 weeks or 5 half-lives (whichever is longer) before the first dose of study medication, including but not limited to the following drugs: rifampin, rifabutin, glucocorticoids, carbamazepine, phenytoin, and phenobarbital
* Strenuous activity, sunbathing or contact sports are not allowed from 4 days prior to study start until the end of the study
* 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
* Donation of blood over 450 milliliters (mL) within 45 days prior to screening

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, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of Alectinib
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
measure: Maximum Observed Plasma Concentration (Cmax) of Alectinib
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
Secondary outcomes:
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
measure: Cmax of RO5468924
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
measure: Tmax of RO5468924
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
measure: AUC(0-inf) of RO5468924
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
measure: AUC(0-last) of RO5468924
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
measure: Plasma Terminal Half-Life (t1/2) of Alectinib and RO5468924
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
measure: Elimination Rate Constant (Kel) of Alectinib and RO5468924
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
measure: Total Molar Concentration of Alectinib and RO5468924 as Derived by AUC(0-inf)
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
measure: Total Molar Concentration of Alectinib and RO5468924 as Derived by Cmax
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
measure: Total Molar Concentration of Alectinib and RO5468924 as Derived by AUC(0-last)
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
measure: Apparent Oral Clearance (CL/F) of Alectinib
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
measure: Apparent Volume of Distribution (Vz/F) of Alectinib
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
measure: Percent Extrapolated AUC(0-inf) (AUC%Extrap[0-inf]) for Alectinib and RO5468924
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
measure: Adjusted r^2 Value (Rsq) for Regression Estimation of Kel for Alectinib and RO5468924
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
measure: Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for AUC(0-inf)
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
measure: Molecular Weight Adjusted M/P Ratio for AUC(0-last)
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
measure: Molecular Weight Adjusted M/P Ratio for Cmax
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
measure: Time to Reach Last Quantifiable Plasma Concentration (Tlast) of Alectinib and RO5468924
timeFrame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose
Other outcomes:
Locations:
city: Austin
country: United States
state: Texas
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: