A Cross-over Study Examining the Bioequivalence of 3 Test Formulations to a Reference Formulation of Alectinib (RO5424802) in Healthy Volunteers

Roche

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteer

Treatments: Drug: Ro542-4802/F03 (Reference); Drug: Ro542-4802/F07 (Test); Drug: Ro542-4802/F08 (Test); Drug: Ro542-4802/F14 (Test)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02074553

NP29040

Details and patient eligibility

About

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.

Enrollment: 97 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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97 participants in 4 patient groups

Ro542-4802/F03;Ro542-4802/F07;Ro542-4802/F14;Ro542-4802/F08

Experimental group

Description:

Participants will receive Ro542-4802/F03 (containing 50% SLS) capsules orally on Day 1 of first intervention period; then Ro542-4802/F07 (containing 25% SLS) capsules orally on Day 1 of second intervention period; then Ro542-4802/F14 (containing 12.5% SLS) capsules orally on Day 1 of third intervention period; followed by Ro542-4802/F08 (containing 3% SLS) capsules orally on Day 1 of fourth intervention period during both fasted (Part 1) and fed (Part 2) conditions. A washout period of at least 10 days will be maintained between each period.

Treatment:

Drug: Ro542-4802/F14 (Test)

Drug: Ro542-4802/F08 (Test)

Drug: Ro542-4802/F03 (Reference)

Drug: Ro542-4802/F07 (Test)

Ro542-4802/F07;Ro542-4802/F08;Ro542-4802/F03;Ro542-4802/F14

Experimental group

Description:

Participants will receive Ro542-4802/F07 (containing 25% SLS) capsules orally on Day 1 of first intervention period; then Ro542-4802/F08 (containing 3% SLS capsules orally on Day 1 in second intervention period; then Ro542-4802/F03 (containing 50% SLS) (containing 12.5% SLS) capsules orally on Day 1 of third intervention period; followed by Ro542-4802/F14 (containing 12.5% SLS) capsules orally on Day 1 of the fourth intervention period during both fasted (Part 1) and fed (Part 2) conditions. A washout period of at least 10 days will be maintained between each period.

Treatment:

Drug: Ro542-4802/F14 (Test)

Drug: Ro542-4802/F08 (Test)

Drug: Ro542-4802/F03 (Reference)

Drug: Ro542-4802/F07 (Test)

Ro542-4802/F08;Ro542-4802/F14;Ro542-4802/F07;Ro542-4802/F03

Experimental group

Description:

Participants will receive Ro542-4802/F08 (containing 3% SLS) capsules orally on Day 1 of first intervention period; then Ro542-4802/F14 (containing 12.5% SLS) capsules orally on Day 1 in second intervention period; then Ro542-4802/F07 (containing 25% SLS) capsules orally on Day 1 of third intervention period; followed by Ro542-4802/F03 (containing 50% SLS) capsules orally on Day 1 of the fourth intervention period during both fasted (Part 1) and fed (Part 2) conditions. A washout period of at least 10 days will be maintained between each period.

Treatment:

Drug: Ro542-4802/F14 (Test)

Drug: Ro542-4802/F08 (Test)

Drug: Ro542-4802/F03 (Reference)

Drug: Ro542-4802/F07 (Test)

Ro542-4802/F14;Ro542-4802/F03;Ro542-4802/F08;Ro542-4802/F07

Experimental group

Description:

Participants will receive Ro542-4802/F14 (containing 12.5% SLS) capsules orally on Day 1 of first intervention period; then Ro542-4802/F03 (containing 50% SLS) capsules orally on Day 1 in second intervention period; then Ro542-4802/F08 (containing 3% SLS) capsules orally on Day 1 of third intervention period; followed by Ro542-4802/F07 (containing 25% SLS) capsules orally on Day 1 of the fourth intervention period during both fasted (Part 1) and fed (Part 2) conditions. A washout period of at least 10 days will be maintained between each period.

Treatment:

Drug: Ro542-4802/F14 (Test)

Drug: Ro542-4802/F08 (Test)

Drug: Ro542-4802/F03 (Reference)

Drug: Ro542-4802/F07 (Test)