Back to resultsBioavailability of GDC-0134 and the Effect of Food and Proton Pump Inhibitor on Pharmacokinetics of GDC-0134 in Healthy Female Participants
Primary Purpose
Amyotrophic Lateral Sclerosis
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Reference capsule GDC-0134
Prototype capsule GDC-0134
rabeprazole
Sponsored by
About this trial
This is an interventional treatment trial for Amyotrophic Lateral Sclerosis
Eligibility Criteria
Inclusion Criteria:
- Healthy female participants between 30 and 65 years of age, inclusive;
- Within body mass index range 18.0 to 35.0 kilograms per square meter (kg/m^2), inclusive;
- Female participants will be of non-childbearing potential;
- In good health, determined by no clinically significant findings from medical history, 12-lead echocardiogram (ECG), and vital signs;
- Clinical laboratory evaluations within the reference range for the test laboratory, unless deemed not clinically significant by the investigator;
- Normal ophthalmology assessment.
Exclusion Criteria:
- Males and females of childbearing potential;
- Significant history or clinical manifestation of any significant metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal (GI), 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;
- History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs;
- History of GI bleeding or GI ulcers;
- Any personal or family history of bleeding disorders, and any personal use of drugs known to affect blood clotting within 30 days of dosing;
- Any acute or chronic medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the subject's safe participation in and completion of the study.
Sites / Locations
- Quotient Clinical Ltd, Clinical Research Unit
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Treatment Sequence 1: ABC1D1
Treatment Sequence 2: ABC2D2
Treatment Sequence 3: BAC1D1
Treatment Sequence 4: BAC2D2
Arm Description
Single dose of reference capsule GDC-0134 (Treatment A) during Period 1. Single dose of prototype capsule GDC-0134 (Treatment B) during Period 2. Single dose of GDC-0134 prototype capsule administered as GDC-0134-in-applesauce preparation under fasting conditions (Treatment C1) during Period 3. Single dose of GDC-0134 prototype capsule administered under fasting conditions in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D1) during Period 4. The washout period between doses will be a minimum of 21 days.
Single dose of reference capsule GDC-0134 (Treatment A) during Period 1. Single dose of prototype capsule GDC-0134 (Treatment B) during Period 2. Single dose of GDC-0134 prototype capsule administered after a high-fat meal (Treatment C2) during Period 3. Single dose of GDC-0134 prototype capsule administered after a high-fat meal in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D2) during Period 4. The washout period between doses will be a minimum of 21 days.
Single dose of prototype capsule GDC-0134 (Treatment B) during Period 1. Single dose of reference capsule GDC-0134 (Treatment A) during Period 2. Single dose of GDC-0134 prototype capsule administered as GDC-0134-in-applesauce preparation under fasting conditions (Treatment C1) during Period 3. Single dose of GDC-0134 prototype capsule administered under fasting conditions in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D1) during Period 4. The washout period between doses will be a minimum of 21 days.
Single dose of prototype capsule GDC-0134 (Treatment B) during Period 1. Single dose of reference capsule GDC-0134 (Treatment A) during Period 2. Single dose of GDC-0134 prototype capsule administered after a high-fat meal (Treatment C2) during Period 3. Single dose of GDC-0134 prototype capsule administered after a high-fat meal in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D2) during Period 4. The washout period between doses will be a minimum of 21 days.
Outcomes
Primary Outcome Measures
Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of GDC-0134
The AUC0-inf is calculated in a plot of concentration of drug in blood plasma against time and extrapolated to infinity.
Area Under the Plasma Concentration-Time Curve up to Time Tau (AUC0-t) of GDC-0134
The AUC0-t is calculated in a plot of concentration of drug in blood plasma against time and calculated up to the time of the last measurable GDC-0134 concentration.
Maximum Observed Concentration (Cmax) of GDC-0134
Cmax is the maximum observed concentration of drug in blood plasma.
Time to Maximum Concentration (Tmax) of GDC-0134
Tmax is the time elapsed from the time of drug administration to maximum plasma concentration.
Apparent Half-Life (t1/2) of GDC-0134
Half-life is defined as the time required for the drug plasma concentration to be reduced to half.
Secondary Outcome Measures
Percentage of Participants with Adverse Events
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Full Information
NCT ID
NCT03237741
First Posted
July 31, 2017
Last Updated
April 16, 2018
Sponsor
Genentech, Inc.
Collaborators
Quotient Clinical
1. Study Identification
Unique Protocol Identification Number
NCT03237741
Brief Title
Bioavailability of GDC-0134 and the Effect of Food and Proton Pump Inhibitor on Pharmacokinetics of GDC-0134 in Healthy Female Participants
Official Title
A Phase I Open-Label Study to Determine the Relative Bioavailability of GDC-0134 and to Investigate the Effect of Food and Proton Pump Inhibitor on Pharmacokinetics of GDC-0134 in Healthy Female Subjects of Non-childbearing Potential
Study Type
Interventional
2. Study Status
Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
August 7, 2017 (Actual)
Primary Completion Date
December 14, 2017 (Actual)
Study Completion Date
December 14, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
Collaborators
Quotient Clinical
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This study will evaluate the pharmacokinetics and safety of GDC-0134 in healthy female volunteers of non-childbearing potential. The first part of the study will compare the bioavailability of a prototype capsule of GDC-0134 relative to an existing GDC-0134 reference capsule (Periods 1 and 2). The second part of the study will assess the effect of GDC-0134-in-applesauce preparation under fasting conditions, the effect of low and high fat foods as well as the effect of elevated stomach pH via pre-treatment with rabeprazole, a proton pump inhibitor (PPI), under fasted and high-fat meal conditions (Periods 3 and 4).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment Sequence 1: ABC1D1
Arm Type
Experimental
Arm Description
Single dose of reference capsule GDC-0134 (Treatment A) during Period 1. Single dose of prototype capsule GDC-0134 (Treatment B) during Period 2. Single dose of GDC-0134 prototype capsule administered as GDC-0134-in-applesauce preparation under fasting conditions (Treatment C1) during Period 3. Single dose of GDC-0134 prototype capsule administered under fasting conditions in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D1) during Period 4. The washout period between doses will be a minimum of 21 days.
Arm Title
Treatment Sequence 2: ABC2D2
Arm Type
Experimental
Arm Description
Single dose of reference capsule GDC-0134 (Treatment A) during Period 1. Single dose of prototype capsule GDC-0134 (Treatment B) during Period 2. Single dose of GDC-0134 prototype capsule administered after a high-fat meal (Treatment C2) during Period 3. Single dose of GDC-0134 prototype capsule administered after a high-fat meal in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D2) during Period 4. The washout period between doses will be a minimum of 21 days.
Arm Title
Treatment Sequence 3: BAC1D1
Arm Type
Experimental
Arm Description
Single dose of prototype capsule GDC-0134 (Treatment B) during Period 1. Single dose of reference capsule GDC-0134 (Treatment A) during Period 2. Single dose of GDC-0134 prototype capsule administered as GDC-0134-in-applesauce preparation under fasting conditions (Treatment C1) during Period 3. Single dose of GDC-0134 prototype capsule administered under fasting conditions in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D1) during Period 4. The washout period between doses will be a minimum of 21 days.
Arm Title
Treatment Sequence 4: BAC2D2
Arm Type
Experimental
Arm Description
Single dose of prototype capsule GDC-0134 (Treatment B) during Period 1. Single dose of reference capsule GDC-0134 (Treatment A) during Period 2. Single dose of GDC-0134 prototype capsule administered after a high-fat meal (Treatment C2) during Period 3. Single dose of GDC-0134 prototype capsule administered after a high-fat meal in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D2) during Period 4. The washout period between doses will be a minimum of 21 days.
Intervention Type
Drug
Intervention Name(s)
Reference capsule GDC-0134
Intervention Description
Oral administration of a single dose of 200 milligrams (mg) GDC-0134 reference capsule administered as two 100 mg capsules.
Intervention Type
Drug
Intervention Name(s)
Prototype capsule GDC-0134
Intervention Description
Oral administration of a single dose of 200 mg GDC-0134 prototype capsule administered as one 200 mg capsule.
Intervention Type
Drug
Intervention Name(s)
rabeprazole
Intervention Description
Oral administration of 20 mg rabeprazole once daily on Days -3, -2 and -1 as well as on Day 1 two hours prior to each administration of GDC-0134 during Period 4.
Primary Outcome Measure Information:
Title
Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of GDC-0134
Description
The AUC0-inf is calculated in a plot of concentration of drug in blood plasma against time and extrapolated to infinity.
Time Frame
Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
Title
Area Under the Plasma Concentration-Time Curve up to Time Tau (AUC0-t) of GDC-0134
Description
The AUC0-t is calculated in a plot of concentration of drug in blood plasma against time and calculated up to the time of the last measurable GDC-0134 concentration.
Time Frame
Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
Title
Maximum Observed Concentration (Cmax) of GDC-0134
Description
Cmax is the maximum observed concentration of drug in blood plasma.
Time Frame
Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
Title
Time to Maximum Concentration (Tmax) of GDC-0134
Description
Tmax is the time elapsed from the time of drug administration to maximum plasma concentration.
Time Frame
Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
Title
Apparent Half-Life (t1/2) of GDC-0134
Description
Half-life is defined as the time required for the drug plasma concentration to be reduced to half.
Time Frame
Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
Secondary Outcome Measure Information:
Title
Percentage of Participants with Adverse Events
Description
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame
From baseline until 21 days after the last dose of study drug up to approximately 16 weeks
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy female participants between 30 and 65 years of age, inclusive;
Within body mass index range 18.0 to 35.0 kilograms per square meter (kg/m^2), inclusive;
Female participants will be of non-childbearing potential;
In good health, determined by no clinically significant findings from medical history, 12-lead echocardiogram (ECG), and vital signs;
Clinical laboratory evaluations within the reference range for the test laboratory, unless deemed not clinically significant by the investigator;
Normal ophthalmology assessment.
Exclusion Criteria:
Males and females of childbearing potential;
Significant history or clinical manifestation of any significant metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal (GI), 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;
History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs;
History of GI bleeding or GI ulcers;
Any personal or family history of bleeding disorders, and any personal use of drugs known to affect blood clotting within 30 days of dosing;
Any acute or chronic medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the subject's safe participation in and completion of the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Quotient Clinical Ltd, Clinical Research Unit
City
Nottingham
ZIP/Postal Code
NG11 6JS
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Bioavailability of GDC-0134 and the Effect of Food and Proton Pump Inhibitor on Pharmacokinetics of GDC-0134 in Healthy Female Participants
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