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Effect of Food, Rabeprazole, Methotrexate and Formulation on the Pharmacokinetics (PK) of GDC-0853 and the Effect of GDC-0853 on the PK of Methotrexate in Healthy Subjects (QCL117578)

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ClinicalTrials.gov Identifier: NCT02699710
Recruitment Status : Completed
First Posted : March 4, 2016
Last Update Posted : March 2, 2020
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Tracking Information
First Submitted Date  ICMJE March 1, 2016
First Posted Date  ICMJE March 4, 2016
Last Update Posted Date March 2, 2020
Actual Study Start Date  ICMJE September 3, 2015
Actual Primary Completion Date May 26, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 28, 2017)
  • Part 1: Relative Bioavailability of GDC-0853 tablet Compared to GDC-0853 Capsule [ Time Frame: Part 1 (Periods 1 to 2 [Period length=5 days]): Predose (</=1 hour before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose on Day 1; 24, 36 hours postdose on Day 2; 48 hours postdose on Day 3; 72 hours postdose on Day 4 ]
  • Part 1: Area Under the Concentration Time-Curve From Time 0 to Infinity (AUC0-inf) of GDC-0853 Capsule [ Time Frame: Part 1 (Periods 1 to 2 [Period length=5 days]): Predose (</=1 hour before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose on Day 1; 24, 36 hours postdose on Day 2; 48 hours postdose on Day 3; 72 hours postdose on Day 4 ]
  • Part 1: Area Under the Concentration Time-Curve From Time 0 to Last Reported Plasma Concentration (AUC0-t) of GDC-0853 Capsule [ Time Frame: Part 1 (Periods 1 to 2 [Period length=5 days]): Predose (</=1 hour before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose on Day 1; 24, 36 hours postdose on Day 2; 48 hours postdose on Day 3; 72 hours postdose on Day 4 ]
  • Part 1: Maximum Plasma Concentration (Cmax) of GDC-0853 Capsule [ Time Frame: Part 1 (Periods 1 to 2 [Period length=5 days]): Predose (</=1 hour before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose on Day 1; 24, 36 hours postdose on Day 2; 48 hours postdose on Day 3; 72 hours postdose on Day 4 ]
  • Part 1: Time to Maximum Plasma Concentration (Tmax) of GDC-0853 Capsule [ Time Frame: Part 1 (Periods 1 to 2 [Period length=5 days]): Predose (</=1 hour before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose on Day 1; 24, 36 hours postdose on Day 2; 48 hours postdose on Day 3; 72 hours postdose on Day 4 ]
  • Part 1: Apparent half-life (t1/2) of GDC-0853 Capsule [ Time Frame: Part 1 (Periods 1 to 2 [Period length=5 days]): Predose (</=1 hour before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose on Day 1; 24, 36 hours postdose on Day 2; 48 hours postdose on Day 3; 72 hours postdose on Day 4 ]
  • Parts 1 and 2: AUC0-inf of GDC-0853 Tablet [ Time Frame: Parts 1 and 2 (Periods 1 to 2 [Period length=5 days]): Predose (</=1 hour before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose on Day 1; 24, 36 hours postdose on Day 2; 48 hours postdose on Day 3; 72 hours postdose on Day 4 ]
  • Parts 1 and 2: AUC0-t of GDC-0853 Tablet [ Time Frame: Parts 1 and 2 (Periods 1 to 2 [Period length=5 days]): Predose (</=1 hour before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose on Day 1; 24, 36 hours postdose on Day 2; 48 hours postdose on Day 3; 72 hours postdose on Day 4 ]
  • Parts 1 and 2: Cmax of GDC-0853 Tablet [ Time Frame: Parts 1 and 2 (Periods 1 to 2 [Period length=5 days]): Predose (</=1 hour before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose on Day 1; 24, 36 hours postdose on Day 2; 48 hours postdose on Day 3; 72 hours postdose on Day 4 ]
  • Parts 1 and 2: Tmax of GDC-0853 Tablet [ Time Frame: Parts 1 and 2 (Periods 1 to 2 [Period length=5 days]): Predose (</=1 hour before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose on Day 1; 24, 36 hours postdose on Day 2; 48 hours postdose on Day 3; 72 hours postdose on Day 4 ]
  • Parts 1 and 2: Apparent t1/2 of GDC-0853 Tablet [ Time Frame: Parts 1 and 2 (Periods 1 to 2 [Period length=5 days]): Predose (</=1 hour before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose on Day 1; 24, 36 hours postdose on Day 2; 48 hours postdose on Day 3; 72 hours postdose on Day 4 ]
  • Parts 1 and 2: AUC0-inf of GDC-0853 Tablet When Administered With Rabeprazole [ Time Frame: Parts 1 and 2 (Period 3 [Period length=8 days]): Predose (</=1 hour before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose on Day 1; 24, 36 hours postdose on Day 2; 48 hours postdose on Day 3; 72 hours postdose on Day 4 ]
  • Parts 1 and 2: AUC0-t of GDC-0853 Tablet When Administered With Rabeprazole [ Time Frame: Parts 1 and 2 (Period 3 [Period length=8 days]): Predose (</=1 hour before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose on Day 1; 24, 36 hours postdose on Day 2; 48 hours postdose on Day 3; 72 hours postdose on Day 4 ]
  • Parts 1 and 2: Cmax of GDC-0853 Tablet When Administered With Rabeprazole [ Time Frame: Parts 1 and 2 (Period 3 [Period length=8 days]): Predose (</=1 hour before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose on Day 1; 24, 36 hours postdose on Day 2; 48 hours postdose on Day 3; 72 hours postdose on Day 4 ]
  • Parts 1 and 2: Tmax of GDC-0853 Tablet When Administered With Rabeprazole [ Time Frame: Parts 1 and 2 (Period 3 [Period length=8 days]): Predose (</=1 hour before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose on Day 1; 24, 36 hours postdose on Day 2; 48 hours postdose on Day 3; 72 hours postdose on Day 4 ]
  • Parts 1 and 2: Apparent t1/2 of GDC-0853 Tablet When Administered With Rabeprazole [ Time Frame: Parts 1 and 2 (Period 3 [Period length=8 days]): Predose (</=1 hour before dosing), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose on Day 1; 24, 36 hours postdose on Day 2; 48 hours postdose on Day 3; 72 hours postdose on Day 4 ]
  • Part 3: Area Under the Concentration Time-Curve From Time 0 to 24 Hours, Steady State (AUC0-24, ss) of GDC0853 Tablet [ Time Frame: Part 3: Predose (</=1 hour before dosing) on Days 17, 18, 19, 20, 21; 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours postdose on Days 20, 21; 16 hours postdose on Day 21; 24 hours postdose on Day 22 ]
  • Part 3: Maximum Plasma Concentration, Steady State (Cmax, ss) of GDC-0853 Tablet [ Time Frame: Part 3: Predose (</=1 hour before dosing) on Days 17, 18, 19, 20, 21; 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours postdose on Days 20, 21; 16 hours postdose on Day 21; 24 hours postdose on Day 22 ]
  • Part 3: Time to Maximum Plasma Concentration, Steady State (Tmax, ss) of GDC-0853 Tablet [ Time Frame: Part 3: Predose (</=1 hour before dosing) on Days 17, 18, 19, 20, 21; 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours postdose on Days 20, 21; 16 hours postdose on Day 21; 24 hours postdose on Day 22 ]
  • Part 3: Area Under the Concentration Time-Curve From Time 0 to 12 Hours (AUC0-12) of GDC-0853 Tablet When Administered With Methotrexate [ Time Frame: Part 3: Predose (</=1 hour before dosing) on Days 17, 18, 19, 20, 21; 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours postdose on Days 20, 21; 16 hours postdose on Day 21; 24 hours postdose on Day 22 ]
  • Part 3: Cmax of GDC-0853 Tablet When Administered with Methotrexate [ Time Frame: Part 3: Predose (</=1 hour before dosing) on Days 17, 18, 19, 20, 21; 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours postdose on Days 20, 21; 16 hours postdose on Day 21; 24 hours postdose on Day 22 ]
  • Part 3: Tmax of GDC-0853 Tablet When Administered with Methotrexate [ Time Frame: Part 3: Predose (</=1 hour before dosing) on Days 17, 18, 19, 20, 21; 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours postdose on Days 20, 21; 16 hours postdose on Day 21; 24 hours postdose on Day 22 ]
  • Part 3: Area Under the Concentration Time-Curve From Time 0 to 24 Hours (AUC0-24) of Methotrexate When Administered With GDC-0853 [ Time Frame: Part 3: Predose (</=1 hour before dosing) on Days 1, 21; 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours postdose on Days 1, 21; 16 hours postdose on Days 1, 21; 24 hours postdose on Days 2, 22 ]
  • Part 3: Cmax of Methotrexate When Administered with GDC-0853 Tablet [ Time Frame: Part 3: Predose (</=1 hour before dosing) on Days 1, 21; 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 hours postdose on Days 1, 21; 24 hours postdose on Days 2, 22 ]
  • Part 3: Tmax of Methotrexate When Administered with GDC-0853 Tablet [ Time Frame: Part 3: Predose (</=1 hour before dosing) on Days 1, 21; 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 hours postdose on Days 1, 21; 24 hours postdose on Days 2, 22 ]
  • Part 3: Apparent t1/2 of Methotrexate When Administered With GDC-0853 [ Time Frame: Part 3: Predose (</=1 hour before dosing) on Days 1, 21; 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 hours postdose on Days 1, 21; 24 hours postdose on Days 2, 22 ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 1, 2016)
  • GDC-0853: Area under the concentration time-curve from time 0 to infinity (AUC0-inf) [ Time Frame: Parts 1 and 2 (Periods 1 to 3): Pre-dose, and up to 24 hours (a maximum of 10 timepoints) post-dose on Day 1, and Pre-dose on Days 2, 3, 4 ]
  • GDC-0853: Area under the concentration time-curve from time 0 to last reported plasma concentration (AUC0-t) [ Time Frame: Parts 1 and 2 (Periods 1 to 3): Pre-dose, and up to 24 hours (a maximum of 10 timepoints) post-dose on Day 1, and Pre-dose on Days 2, 3, 4 ]
  • GDC-0853: Maximum plasma concentration (Cmax) [ Time Frame: Parts 1 and 2 (Periods 1 to 3): Pre-dose, and up to 24 hours (a maximum of 10 timepoints) post-dose on Day 1, and Pre-dose on Days 2, 3, 4 ]
  • GDC-0853: Time to maximum plasma concentration(Tmax) [ Time Frame: Parts 1 and 2 (Periods 1 to 3): Pre-dose, and up to 24 hours (a maximum of 10 timepoints) post-dose on Day 1, and Pre-dose on Days 2, 3, 4 ]
  • GDC-0853: Apparent half-life (t1/2) [ Time Frame: Parts 1 and 2 (Periods 1 to 3): Pre-dose, and up to 24 hours (a maximum of 10 timepoints) post-dose on Day 1, and Pre-dose on Days 2, 3, 4 ]
  • GDC-0853: Area under the concentration time-curve from time 0 to 24 hours, steady state (AUC0-24, ss) [ Time Frame: Part 3: Pre-dose and up to 24 hours (11 timepoints) post-dose on Day 21 ]
  • GDC-0853: Maximum plasma concentration, steady state (Cmax, ss) [ Time Frame: Part 3: Pre-dose and up to 12 hours (9 timepoints) post-dose on Days 20 and 21 ]
  • GDC-0853: Time to maximum plasma concentration, steady state (Tmax, ss) [ Time Frame: Part 3: Pre-dose and up to 12 hours (9 timepoints) post-dose on Days 20 and 21 ]
  • GDC-0853: Area under the concentration time-curve from time 0 to 12 hours (AUC0-12) [ Time Frame: Part 3: Pre-dose and up to 12 hours (9 timepoints) post-dose on Days 20 and 21 ]
  • Methotrexate: Area under the concentration time-curve from time 0 to 24 hours (AUC0-24) [ Time Frame: Part 3: Pre-dose and up to 24 hours (11 timepoints) post-dose on Days 1 and 21 ]
  • Methotrexate: Maximum plasma concentration (Cmax) [ Time Frame: Part 3: Pre-dose and up to 24 hours (11 timepoints) post-dose on Days 1 and 21 ]
  • Methotrexate: Apparent half-life (t1/2) [ Time Frame: Part 3: Pre-dose and up to 24 hours (11 timepoints) post-dose on Days 1 and 21 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 28, 2017)
Percentage of Participants With Adverse Events [ Time Frame: From Baseline up to approximately 9 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 1, 2016)
Number of participants with adverse events [ Time Frame: Up to approximately 7 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Food, Rabeprazole, Methotrexate and Formulation on the Pharmacokinetics (PK) of GDC-0853 and the Effect of GDC-0853 on the PK of Methotrexate in Healthy Subjects
Official Title  ICMJE A Phase I, Single Center, Randomized, Open-Label, Study Investigating the Effect of Food, Rabeprazole, Methotrexate and Formulation on the Pharmacokinetics of GDC-0853 and the Effect of GDC-0853 on the Pharmacokinetics of Methotrexate in Healthy Subjects
Brief Summary This study is a Phase I, single center, randomized (Parts 1 and 2 only), open-label, 3 part study. Parts 1 and 2 are 2-way crossover, with 1-fixed sequence, 3-period designs to investigate the effect of formulation, food and rabeprazole on the PK of GDC-0853 in healthy male and female (of non-childbearing potential) participants. Part 3 is a fixed-sequence study with 3 treatments to characterize the steady-state PK of the GDC-0853 tablet; the effect of simultaneous administration of a single dose of methotrexate on the steady-state kinetics of GDC-0853; and the effect of dosing GDC-0853 to steady-state on the single dose PK of methotrexate in healthy male participants.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Healthy Volunteer
Intervention  ICMJE
  • Drug: Folic Acid
    Folic acid will be administered orally as tablet at a single dose of 5 mg.
  • Drug: GDC-0853
    GDC-0853 will be administered orally as tablet or capsule at a dose of 200 mg.
  • Drug: Methotrexate
    Methotrexate will be administered orally as tablet at a single dose of 7.5 mg.
  • Drug: Rabeprazole
    Rabeprazole will be administered orally as tablet at a dose of 20 mg.
Study Arms  ICMJE
  • Experimental: Part 1: GDC-0853, Rabeprazole (Fasting State)
    Participants will receive single dose of GDC-0853 (200 milligrams [mg]) in a crossover design as either the capsule or tablet formulation in the fasted state with the final fixed treatment consisting of the tablet formulation administered in the fasted state after prior administration of rabeprazole (20 mg twice daily [BID]) for 3 days.
    Interventions:
    • Drug: GDC-0853
    • Drug: Rabeprazole
  • Experimental: Part 2: GDC-0853, Rabeprazole (Fasting or Fed State)
    Participants will receive single dose of GDC-0853 (200 mg) tablet formulation in the fasted or fed state in a crossover design with the final fixed treatment consisting of the tablet formulation administered in the fed state after prior administration of rabeprazole (20 mg BID) for 3 days.
    Interventions:
    • Drug: GDC-0853
    • Drug: Rabeprazole
  • Experimental: Part 3: GDC-0853, Methotrexate
    Participants will receive single dose of methotrexate (7.5 mg) under fasting conditions on Day 1 (5 mg folic acid will be administered the following day [Day 2]) and then GDC-0853 (200 mg) tablet formulation twice daily (BID) under fasting conditions (an overnight fast for the morning dose and a 2 hour fast for the evening dose) from Days 15 to 20 after washout period from Days 2 to 14. On Day 21, participants will receive single dose of methotrexate (7.5 mg) with single dose of GDC-0853 (200 mg) tablet formulation under fasting conditions, and folic acid (5 mg) will be administered on Day 22.
    Interventions:
    • Drug: Folic Acid
    • Drug: GDC-0853
    • Drug: Methotrexate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 27, 2018)
50
Original Estimated Enrollment  ICMJE
 (submitted: March 1, 2016)
49
Actual Study Completion Date  ICMJE May 26, 2016
Actual Primary Completion Date May 26, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Within body mass index range of 18.0 to 31.0 kilograms per square meter (kg/m^2), inclusive
  • For women who are not postmenopausal (greater than or equal to [>/=] 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): these participants will be excluded
  • For men: agreement to use a condom plus an additional contraceptive method with their partner during the treatment period and for at least 93 days after the last dose of study drug and agreement to refrain from donating sperm during this same period

Exclusion Criteria:

  • Significant history or clinical manifestation of any significant metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder (as determined by the investigator)
  • History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator
  • Participants previously enrolled in this study or participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 90 days prior to Period 1 Check-in (Day -1)
  • History of malignancy, except for completely excised basal cell carcinoma or squamous cell carcinoma of the skin or cervical carcinoma in situ
  • Female participant is pregnant, lactating or breastfeeding
  • Current treatment with medications that are well known to prolong the QT interval
  • Failure to satisfy the investigator of fitness to participate for any other reason
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02699710
Other Study ID Numbers  ICMJE GP29832
2015-002471-25 ( EudraCT Number )
QCL117578 ( Other Identifier: Genentech, Inc. )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Genentech, Inc.
Study Sponsor  ICMJE Genentech, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Genentech, Inc.
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP