Healthy Volunteers
Conditions
Brief summary
This is a two-part study to determine the relative bioavailability of two different prototype capsules of GDC-0134 to that of an existing reference capsule of GDC-0134 under both fed and fasted conditions. The study is open to healthy female participants of non-childbearing potential.
Interventions
DRUGGDC-0134 F09 Formulation
Participants will receive a single oral dose of GDC-0134 reference capsule F09.
DRUGGDC-0134 F15 Formulation
Participants will receive a single oral dose of GDC-0134 prototype capsule F15.
DRUGGDC-0134 F16 Formulation
Participants will receive a single oral dose of GDC-0134 prototype capsule F16.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Body mass index (BMI) range 18.5 to 35 kilograms per square meter (kg/m2) * In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, and vital signs; * Clinical laboratory evaluations within the reference range for the test laboratory, unless deemed not clinically significant by the principal investigators (PIs) * Females of non-childbearing potential only
Exclusion criteria
* History or clinical manifestation of any significant medical condition as determined by the PI (or designee) * History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the PI (or designee) * History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs * Use of any prescription medications/products within 14 days prior to Check-in (Day -1) for their first treatment period and during the entire study duration, unless deemed acceptable by the PI * Use of oral antibiotics within 4 weeks or intravenous antibiotics within 8 weeks prior to the Screening evaluation and during the entire study duration * Use of any over-the-counter, non-prescription preparations within 14 days prior to Check-in (Day -1) for their first treatment period and during the entire study duration, unless deemed acceptable by the PI * Use of acid reducing medications (proton pump inhibitors \[PPIs\], histamine H2-receptor antagonists \[H2RAs\]) within 14 days prior to Check-in (Day -1) for their first treatment period and during the entire study duration. As an alternative, antacids may be allowed at least 4 hours before or after dose * Use of any vaccines (including seasonal flu and H1N1 vaccines) within 14 days prior to Check-in (Day -1) for their first treatment period * Use of tobacco- or nicotine-containing products within 6 months prior to Check-in (Day -1) for their first treatment period and during the entire study * Any acute or chronic condition or any other reason that, in the opinion of the PI, would limit the subject's ability to complete and/or participate in this clinical study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Observed Concentration (Cmax) of GDC-0134. | The time points at which the outcome measure was assessed were 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 336, 504 hours post-dose. |
| Area Under the Curve Extrapolated to Infinity (AUCinf) of GDC-0134 | The time points at which the outcome measure was assessed were 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 336, 504 hours post-dose. |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Adverse Events (AEs) | From baseline through the end of study (approximately 11 weeks) |
Countries
United States
Participant flow
Recruitment details
Screening period: Day -28 to Day 2
Participants by arm
| Arm | Count |
|---|---|
| Part I: GDC-0134 F09 vs GDC-0134 F16 Capsule Formulation In Part 1 participants received single doses of either GDC-0134 F09 capsules (prototype) or GDC-0134 F16 capsules (reference) after having consumed a standard meal. | 9 |
| Part 1: GDC-0134 F16 vs GDC-0134 F09 Capsule Formulation In Part 1, participants received a single dose of either GDC-0134 F16 capsules or GDC-0134 F09 capsules after after having consumed a standard meal. | 10 |
| Part 2: GDC-0134 F09 vs GDC-0134 F15 Capsule Formulation In Part 2 participants received single doses of either GDC-0134 F09 or GDC-0134 F15 capsules (prototype) in fasting conditions. | 9 |
| Part 2: GDC-0134 F15 vs GDC-0134 F09 Capsule Formulation In Part 2 participants received single doses of either GDC-0134 F15 or GDC-0134 F09 capsules (prototype) in fasting conditions. | 10 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Part 2: GDC-0134 F15 vs GDC-0134 F09 Capsule Formulation | Part I: GDC-0134 F09 vs GDC-0134 F16 Capsule Formulation | Part 2: GDC-0134 F09 vs GDC-0134 F15 Capsule Formulation | Part 1: GDC-0134 F16 vs GDC-0134 F09 Capsule Formulation |
|---|---|---|---|---|---|
| Age, Continuous | 56.1 Years STANDARD_DEVIATION 6.4 | 58.8 Years STANDARD_DEVIATION 3.1 | 56.3 Years STANDARD_DEVIATION 8.9 | 52.6 Years STANDARD_DEVIATION 7.2 | 56.5 Years STANDARD_DEVIATION 4.8 |
| BMI | 27.8 kg/m^2 STANDARD_DEVIATION 4.6 | 27.9 kg/m^2 STANDARD_DEVIATION 5.1 | 28.1 kg/m^2 STANDARD_DEVIATION 4.2 | 159.1 kg/m^2 STANDARD_DEVIATION 4.4 | 26.7 kg/m^2 STANDARD_DEVIATION 5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 4 Participants | 3 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 6 Participants | 6 Participants | 6 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 160.9 cm STANDARD_DEVIATION 6.2 | 160.6 cm STANDARD_DEVIATION 5 | 162.9 cm STANDARD_DEVIATION 7.6 | 159.1 cm STANDARD_DEVIATION 6.6 | 161.2 cm STANDARD_DEVIATION 5.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 2 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 30 Participants | 8 Participants | 8 Participants | 7 Participants | 7 Participants |
| Sex: Female, Male Female | 38 Participants | 10 Participants | 9 Participants | 9 Participants | 10 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Weight | 72.0 kg STANDARD_DEVIATION 12 | 71.5 kg STANDARD_DEVIATION 10 | 74.5 kg STANDARD_DEVIATION 12.5 | 73.4 kg STANDARD_DEVIATION 15.6 | 68.9 kg STANDARD_DEVIATION 10.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 19 |
| other Total, other adverse events | 10 / 19 | 10 / 19 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 |
Outcome results
Primary
Area Under the Curve Extrapolated to Infinity (AUCinf) of GDC-0134
Time frame: The time points at which the outcome measure was assessed were 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 336, 504 hours post-dose.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 GDC-0134 F16 Capsule Fed | Area Under the Curve Extrapolated to Infinity (AUCinf) of GDC-0134 | 190 uM.h | Geometric Coefficient of Variation 78.7 |
| Part 1 GDC-0134 F09 Capsule Fed | Area Under the Curve Extrapolated to Infinity (AUCinf) of GDC-0134 | 154 uM.h | Geometric Coefficient of Variation 94.9 |
| Part 2 GDC-0134 F15 Fasted | Area Under the Curve Extrapolated to Infinity (AUCinf) of GDC-0134 | 84.8 uM.h | Geometric Coefficient of Variation 103.4 |
| Part 2 GDC-0134 F09 Capsule Fasted | Area Under the Curve Extrapolated to Infinity (AUCinf) of GDC-0134 | 85.6 uM.h | Geometric Coefficient of Variation 103.9 |
90% CI: [1.1175, 1.3327]
90% CI: [0.8266, 1.1968]
Primary
Maximum Observed Concentration (Cmax) of GDC-0134.
Time frame: The time points at which the outcome measure was assessed were 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 336, 504 hours post-dose.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 GDC-0134 F16 Capsule Fed | Maximum Observed Concentration (Cmax) of GDC-0134. | 5.56 uM | Geometric Coefficient of Variation 85.2 |
| Part 1 GDC-0134 F09 Capsule Fed | Maximum Observed Concentration (Cmax) of GDC-0134. | 4.45 uM | Geometric Coefficient of Variation 93.7 |
| Part 2 GDC-0134 F15 Fasted | Maximum Observed Concentration (Cmax) of GDC-0134. | 2.66 uM | Geometric Coefficient of Variation 131.5 |
| Part 2 GDC-0134 F09 Capsule Fasted | Maximum Observed Concentration (Cmax) of GDC-0134. | 2.68 uM | Geometric Coefficient of Variation 140.1 |
90% CI: [1.1149, 1.3951]
90% CI: [0.8531, 1.1405]
Secondary
Percentage of Participants With Adverse Events (AEs)
Time frame: From baseline through the end of study (approximately 11 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 GDC-0134 F16 Capsule Fed | Percentage of Participants With Adverse Events (AEs) | 63.2 Percentage of Participants |
| Part 1 GDC-0134 F09 Capsule Fed | Percentage of Participants With Adverse Events (AEs) | 52.6 Percentage of Participants |