A Study to Investigate the Effect of Esomeprazole and the Effect of Food on the Pharmacokinetics of Balovaptan in Healthy Volunteers

A Single-Center, Part-Randomized, Open-Label, Single-Dose, Three-Period, Crossover Study to Investigate the Effect of Esomeprazole and The Effect of Food on the Pharmacokinetics of Balovaptan in Healthy Volunteers

This study will investigate the effect of food and the effect of esomeprazole on the pharmacokinetics (PK) of a single dose of balovaptan in healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Drug: Balovaptan; Drug: Esomeprazole

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • PRA International Clinical Pharmacology Center (EDS US Clinic)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• No evidence of any active or chronic disease
• Body mass index (BMI) between 18 and 32 kg/m2 inclusive, at screening
• For women of childbearing potential: if engaging in heterosexual activity, agreement to use at least two adequate forms of contraception during the entire study and for 90 days following the last dose of study drug
• For men: agreement to use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria:

• Pregnancy or lactation (positive serum pregnancy test at screening or at admission)
• Any condition or disease detected during the medical interview/physical examination that would render the subject unsuitable for the study, place the subject at undue risk or interfere with the ability of the subject to complete the study in the opinion of the Investigator
• In the opinion of the Investigator, any major illness within 4 weeks prior to the screening examination or any febrile illness within 1 week prior to screening.
• History of any clinically significant, as determined by the investigator, gastrointestinal, renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardiovascular, endocrinological, hematological, lymphatic, musculoskeletal, genitourinary, immunological, dermatological, or connective tissue or allergic disease, metabolic disorder, or cancer
• Signs and symptoms potentially indicative of peripheral neuropathy
• History or evidence of any medical condition potentially altering the absorption, distribution, metabolism, or elimination of drugs
• A history of clinically significant in the opinion of the Investigator hypersensitivity
• History or presence of clinically significant ECG abnormalities before study drug administration
• Clinically significant abnormalities in laboratory test results
• History of coagulopathies, bleeding disorders, or blood dyscrasias
• Current suicidal risk, in the opinion of the Investigator
• Unexplained syncope during the 6 months prior to screening or with presyncopal and/or syncopal symptoms during orthostatic challenge testing
• Current smoker or user of tobacco or nicotine-containing products or subjects who have smoked or used tobacco or nicotine-containing products within 3 months prior to first study drug administration
• Suspicion of or presence of a clinically relevant history of or current alcohol and/or other substance abuse or addiction.
• Alcohol consumption of >14 units per week for males and females
• Positive urine alcohol test or urine drug screen at screening or Day -1 of any treatment period
• Hormone replacement therapy if postmenopausal status cannot be ascertained from medical history or FSH levels
• Clinically relevant deviation from normal in the physical examination including vital signs, as determined by the investigator
• Positive result for HIV 1, HIV 2, hepatitis C virus antibody, or hepatitis B core (HBc) antibody.
• Participation in an investigational drug or device study within 4 weeks or 5 times the elimination half-life, whichever is longer, prior to first dosing, or within 5 months prior to first administration of study drug in case of a study with a biological, as calculated from the day of Follow-up visit from the previous study
• Donation of blood or plasma or significant blood loss within 3 months prior to screening
• Dietary restrictions that would prohibit the consumption of standardized meals or the highfat, high-calorie meal planned for this study
• Use of any prohibited medications or food before study start or subjects who do not agree to refrain from consuming prohibited medications or food during the study
• Conditions requiring concomitant medication during the study (including for dental conditions).
• Any prescribed systemic or topical medication within 4 weeks (or within 5 times the elimination half-life of the medication, whichever is longer) of the first administration of study drug
• Used any nonprescribed systemic or topical medication or herbal remedies within 7 days before the first study drug administration
• Received any medications known to chronically alter drug absorption or elimination processes within 4 weeks before the first administration of study drug
• Use of any drugs or substances, including herbal treatments such as St John's wort, that are known to be substrates, inducers, or inhibitors of CYP3A4 within 4 weeks before the first administration of study drug
• Use of any drugs or substances, including herbal treatments, such as fluoxetine, fluvoxamine, aspirin, norethisterone, rifampicin, etc that are known to be substrates, inducers, or inhibitors of CYP2C19 within 4 weeks before the first administration of study drug
• Subjects under judicial supervision, guardianship, or curatorship
• Poor venous access for blood sampling
• Participants who are intolerant to sucrose
• Previous exposure to balovaptan

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment sequence ABC; In Period 1 participants will receive 1 tablet of balovaptan after high-fat, high-calorie meal. In Period 2, after 12 to 21 days wash-out, participants will receive 1 tablet of balovaptan after 10-hour fast. In Period 3 participants will receive esomeprazole administered once daily for 6 days and with a single oral dose of balovaptan in the fasted state 1 hour after the fifth esomeprazole dose	Drug: Balovaptan; Balovaptan will be administered after a high-fat, high-calorie meal (Treatment A), after a 10-hour fast (Treatment B), and after a 10-hour fast with esomeprazole 40 mg (Treatment C); Drug: Esomeprazole; Esomeprazole will be administered once daily for 6 days and with a single dose of balovaptan 1 hour after the fifth esomeprazole dose
EXPERIMENTAL: Treatment sequence BAC; In Period 1 participants will receive 1 tablet of balovaptan after 10-hour fast. In Period 2, after 12 to 21 days wash-out, participants will receive 1 tablet of balovaptan after high-fat, high-calorie meal. In Period 3 participants will receive esomeprazole administered once daily for 6 days and with a single oral dose of balovaptan in the fasted state 1 hour after the fifth esomeprazole dose	Drug: Balovaptan; Balovaptan will be administered after a high-fat, high-calorie meal (Treatment A), after a 10-hour fast (Treatment B), and after a 10-hour fast with esomeprazole 40 mg (Treatment C); Drug: Esomeprazole; Esomeprazole will be administered once daily for 6 days and with a single dose of balovaptan 1 hour after the fifth esomeprazole dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) of Balovaptan	Maximum plasma concentration of Balovaptan is estimated using non-compartmental methods. Observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Mean Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of Balovaptan	Area under the plasma concentration-time curve (time 0 to infinity) of Balovaptan is estimated using non-compartmental methods from the concentration-time profiles. Percent extrapolation less than or equal to 20% is required to obtain a reliable AUC0-inf.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of Balovaptan	Area under the plasma concentration-time curve of Balovaptan from time 0 to 24 hours post-dose is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post dose
Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Balovaptan	Area under the concentration-time curve (time 0 to time of last quantifiable concentration) of Balovaptan is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Time to Reach Cmax in Plasma (Tmax) of Balovaptan	Time to maximum plasma concentration of Balovaptan is defined as first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units and estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Last Quantifiable Concentration (Clast) of Balovaptan	Last quantifiable concentration is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Time To the Last Quantifiable Concentration (Tlast) of Balovaptan	Time to last quantifiable concentration is based on last detectable concentration in the time curve.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Time Between Dosing and Time of First Balovaptan Plasma Concentration (Tlag)	Time between dosing and time of first balovaptan plasma concentration is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Apparent Clearance (Cl/F) of Balovaptan	Apparent clearance is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Apparent Volume of Distribution (Vd/F) of Balovaptan	Apparent volume of distribution is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Terminal Elimination Phase Half-Life (T1/2) of Balovaptan	Terminal phase half-life expressed in time units is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Terminal Phase Rate Constant (λz) of Balovaptan	Terminal phase rate constant is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Plasma Concentrations of Balovaptan	Amount of Balovaptan in a given volume of plasma.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) of M2 Metabolite	Maximum plasma concentration of M2 Metabolite is estimated using non-compartmental methods. Observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Maximum Plasma Concentration (Cmax) of M3 Metabolite	Maximum plasma concentration of M3 Metabolite is estimated using non-compartmental methods. Observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Maximum Plasma Concentration (Cmax) of Esomeprazole	Maximum plasma concentration of Esomeprazole is estimated using non-compartmental methods. Observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units	Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose
Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of M2 Metabolite	Area under the plasma concentration-time curve (time 0 to infinity) of M2 Metabolite is estimated using non-compartmental methods from the concentration-time profiles. Percent extrapolation less than or equal to 20% is required to obtain a reliable AUC0-inf.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of M3 Metabolite	Area under the plasma concentration-time curve (time 0 to infinity) of M3 Metabolite is estimated using non-compartmental methods from the concentration-time profiles. Percent extrapolation less than or equal to 20% is required to obtain a reliable AUC0-inf.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Area Under the Concentration-Time Curve From Time Extrapolated to Infinity (AUC (0-inf)) of Esomeprazole	Area under the plasma concentration-time curve (time 0 to infinity) of Esomeprazole is estimated using non-compartmental methods from the concentration-time profiles. Percent extrapolation less than or equal to 20% is required to obtain a reliable AUC0-inf.	Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose
Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of M2 Metabolite	Area under the plasma concentration-time curve of M2 Metabolite from time 0 to 24 hours post-dose is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post dose
Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC(0-24h)) of M3 Metabolite	Area under the plasma concentration-time curve of M3 Metabolite from time 0 to 24 hours post-dose is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post dose
Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of M2 Metabolite	Area under the concentration-time curve (time 0 to time of last quantifiable concentration) of M2 Metabolite is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of M3 Metabolite	Area under the concentration-time curve (time 0 to time of last quantifiable concentration) of M3 Metabolite is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Esomeprazole	Area under the concentration-time curve (time 0 to time of last quantifiable concentration) of Esomeprazole is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose
Time to Reach Cmax in Plasma (Tmax) of M2 Metabolite	Time to maximum plasma concentration of M2 Metabolite is defined as first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units and estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Time to Reach Cmax in Plasma (Tmax) of M3 Metabolite	Time to maximum plasma concentration of M3 Metabolite is defined as first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units and estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Time to Reach Cmax in Plasma (Tmax) of Esomeprazole	Time to maximum plasma concentration of Esomeprazole is defined as first observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in time units and estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose
Last Quantifiable Concentration (Clast) of M2 Metabolite	Last quantifiable concentration is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Last Quantifiable Concentration (Clast) of M3 Metabolite	Last quantifiable concentration is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Last Quantifiable Concentration (Clast) of Esomeprazole	Last quantifiable concentration is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose
Time To the Last Quantifiable Concentration (Tlast) of M2 Metabolite	Time to last quantifiable concentration is based on last detectable concentration in the time curve.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Time To the Last Quantifiable Concentration (Tlast) of M3 Metabolite	Time to last quantifiable concentration is based on last detectable concentration in the time curve.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Time To the Last Quantifiable Concentration (Tlast) of Esomeprazole	Time to last quantifiable concentration is based on last detectable concentration in the time curve.	Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose
Terminal Elimination Phase Half-Life (T1/2) of M2 Metabolite	Terminal phase half-life expressed in time units is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Terminal Elimination Phase Half-Life (T1/2) of M3 Metabolite	Terminal phase half-life expressed in time units is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Terminal Elimination Phase Half-Life (T1/2) of Esomeprazole	Terminal phase half-life expressed in time units is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose
Percentage of Patricipants With Adverse Events (AEs)		Randomization to end of study (up to approximately 7 weeks)
Terminal Phase Rate Constant (λz) of M2 Metabolite	Terminal phase rate constant is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Terminal Phase Rate Constant (λz) of M3 Metabolite	Terminal phase rate constant is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Terminal Phase Rate Constant (λz) of Esomeprazole	Terminal phase half-life expressed in time units is estimated using non-compartmental methods from the concentration-time profiles.	Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose
Plasma Concentrations of M2 Analyte	Amount of M2 Analyte in a given volume of plasma.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Plasma Concentrations of M3 Analyte	Amount of M3 Analyte in a given volume of plasma.	Samples at predose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, and 192 hours post dose
Plasma Concentrations of Esomeprazole	Amount of Esomeprazole in a given volume of plasma.	Samples at predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 19, 2019
• Primary Completion (ACTUAL): December 24, 2019
• Study Completion (ACTUAL): January 6, 2020

Study Registration Dates

• First Submitted: November 6, 2019
• First Submitted That Met QC Criteria: November 6, 2019
• First Posted (ACTUAL): November 7, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 16, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Esomeprazole
• Other Study ID Numbers: WP41047

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No