Healthy Volunteers
Conditions
Brief summary
This study will be an open-label, randomized, three-period, six-sequence crossover study of GDC-9545 administered to healthy females of non-childbearing potential to determine the relative bioavailability of the Phase 3 capsule formulation to the Phase 1 tablet formulation in the fasted state and the effect of food on the Phase 3 capsule formulation.
Interventions
DRUGGDC-9545 Tablet, Fasted: Treatment A
One dose of the GDC-9545 Phase 1 reference tablet formulation (three 10-mg tablets) administered orally with approximately 240 mL room temperature water after at least an 8-hour fast.
DRUGGDC-9545 Capsule, Fasted: Treatment B
One dose of the GDC-9545 Phase 3 capsule formulation (one 30-mg capsule) administered orally with approximately 240 mL room temperature water after at least an 8-hour fast.
DRUGGDC-9545 Capsule, Fed: Treatment C
One dose of the GDC-9545 Phase 3 capsule formulation (one 30-mg capsule) administered orally with approximately 240 mL room temperature water within 30 minutes of eating a high-fat meal.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Females of non-childbearing potential including non-pregnant, non-lactating, and either postmenopausal or surgically sterile for at least 90 days prior to screening, as defined in the protocol * Body mass index (BMI) from 18.5 to 30.0 kilograms per square metre of body surface area (kg/m\^2) at screening * In good health, determined by no clinically significant findings from medical history, 12-lead ECG, or vital signs * Clinical laboratory evaluations within the reference range for the test laboratory, unless deemed not clinically significant by the investigator * Negative test for selected drugs of abuse at Screening (does not include alcohol) and at Check-in (Day -1) for Period 1 (does include alcohol) * Negative hepatitis panel (hepatitis B surface antigen and hepatitis C virus antibody) and negative human immunodeficiency virus (HIV) antibody screens * Subject must receive an explanation of the mandatory Research Biosample Repository (RBR) component of the study and be able to comprehend and willing to sign an Informed Consent Form (ICF)
Exclusion criteria
* Significant history or clinical manifestation of any 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 allergy to GDC-9545 or any of its excipients * History of stomach or intestinal surgery (including cholecystectomy) or resection that would potentially alter absorption and/or excretion of orally administered drugs (except that appendectomy and hernia repair will be allowed) * History or presence of an abnormal ECG that, in the investigator's opinion, is clinically significant including complete left bundle branch block; right bundle branch block; first-, second-, or third-degree heart block; sick sinus syndrome; or evidence of prior myocardial infarction * Having a QTc interval greater than (\>)470 milliseconds (msec), PR interval \>210 msec, or QRS complex \>120 msec * Confirmed (e.g., 2 consecutive measurements) baseline heart rate ≤50 beats per minute (bpm) prior to enrollment * History of alcoholism or drug addiction within 1 year prior to Check-in (Day -1) of Period 1 * The use of tobacco- or nicotine-containing products within 6 months prior to Check-in (Day -1) of Period 1 * History of active or latent tuberculosis (TB), regardless of treatment history * History of previous use of tamoxifen, aromatase inhibitors, or any other endocrine agent for the treatment of breast cancer * The use of hormone replacement therapy or selective ER modulators (SERMs; e.g., raloxifene) within 1 year prior to Check-in (Day -1) of Period 1 * The use of oral antibiotics within 4 weeks or intravenous antibiotics within 8 weeks prior to Check-in (Day -1) of Period 1 * The use or intent to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to Check-in (Day -1) of Period 1 * The participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 5 half-lives or 30 days, whichever is longer, prior to Check-in (Day -1) of Period 1 * The use of drugs of abuse (including opioids) within 4 weeks of Screening * The use of any prescription medications/products within 14 days prior to Check-in (Day -1) of Period 1, unless deemed acceptable by the investigator * The use of any over-the-counter, non-prescription preparations (including vitamins; minerals; and phytotherapeutic-, herbal-, and plant-derived preparations) within 7 days prior to Check-in (Day -1) of Period 1, unless deemed acceptable by the investigator * The use of poppy seed-containing foods or beverages within 7 days prior to Check-in (Day -1) of Period 1, unless deemed acceptable by the investigator * The use of alcohol- or caffeine-containing foods or beverages within 72 hours prior to Check-in (Day -1) of Period 1, unless deemed acceptable by the investigator * Not refraining from strenuous exercise from 7 days prior to Check-in (Day -1) of Period 1 * The need to follow a special diet and unable to consume the high-fat meal * Poor peripheral venous access * History of malignancy, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer (must be cancer-free for at least 5 years) * Donation of blood from 90 days prior to Screening through Follow-up, inclusive, or of plasma from 2 weeks prior to Screening * Receipt of blood products within 2 months prior to Check-in (Day -1) of Period 1 * Any acute or chronic condition that, in the opinion of the investigator, would limit the subject's ability to complete and/or participate in this clinical study * In the opinion of the investigator or Sponsor, are unsuitable for inclusion in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of GDC-9545 | Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days) | The pharmacokinetics parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin. |
| Time to Maximum Observed Plasma Concentration (Tmax) of GDC-9545 | Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days) | The pharmacokinetics (PK) parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin. The parameter tmax was analyzed nonparametrically using the Wilcoxon signed-rank test. The median difference between the test and reference investigational products (GDC-9545 Phase 3 capsule formulation compared to a Phase 1 tablet formulation under fasted conditions \[Treatment B vs. Treatment A\] and the food effect on GDC-9545 PK for a Phase 3 capsule formulation \[Treatment C vs. Treatment B\]) and the corresponding 90% confidence interval were calculated. |
| Time of Last Quantifiable Plasma Concentration (Tlast) of GDC-9545 | Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days) | The pharmacokinetics parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin. |
| Time to First Quantifiable Plasma Concentration (Tlag) of GDC-9545 | Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days) | The pharmacokinetics parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin. |
| Area Under the Plasma Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of GDC-9545 | Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days) | The pharmacokinetics (PK) parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin. The PK parameters Cmax, AUC0-t, and AUC0-∞ for GDC-9545 were analyzed to evaluate the relative bioavailability of GDC-9545 as a Phase 3 capsule formulation compared to a Phase 1 tablet formulation under fasted conditions (Treatment B vs. Treatment A) and to assess the food effect on GDC-9545 PK for a Phase 3 capsule formulation (Treatment C vs. Treatment B). The mixed-effect analysis of variance model for three-period crossover design was used for formulation comparison and fasted state and fed state comparison of capsule. The model included sequence, formulation, and period as fixed effects and a random effect for subject within sequence. An unstructured covariance structure was to be used; however, if it failed to converge, an alternative covariance structure may have been applied. |
| Area Under the Plasma Concentration-Time Curve From Hour 0 Extrapolated to Infinity (AUC0-∞) of GDC-9545 | Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days) | The pharmacokinetics (PK) parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin. The PK parameters Cmax, AUC0-t, and AUC0-∞ for GDC-9545 were analyzed to evaluate the relative bioavailability of GDC-9545 as a Phase 3 capsule formulation compared to a Phase 1 tablet formulation under fasted conditions (Treatment B vs. Treatment A) and to assess the food effect on GDC-9545 PK for a Phase 3 capsule formulation (Treatment C vs. Treatment B). The mixed-effect analysis of variance model for three-period crossover design was used for formulation comparison and fasted state and fed state comparison of capsule. The model included sequence, formulation, and period as fixed effects and a random effect for subject within sequence. An unstructured covariance structure was to be used; however, if it failed to converge, an alternative covariance structure may have been applied. |
| Percentage of Area Under the Plasma Concentration-Time Curve (AUC) That is Due to Extrapolation From Last Measurable Concentration to Infinity (%AUCextrap) of GDC-9545 | Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days) | The pharmacokinetics parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin. |
| Apparent Terminal Elimination Rate Constant (λz) of GDC-9545 | Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days) | The pharmacokinetics parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin. The apparent terminal elimination rate constant (λz) is the magnitude of the slope of the linear regression of the log concentration versus time profile during the terminal phase. |
| Apparent Terminal Elimination Half-Life (t1/2) of GDC-9545 | Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days) | The pharmacokinetics parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin. |
| Apparent Total Clearance (CL/F) of GDC-9545 | Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days) | The pharmacokinetics parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin. |
| Maximum Observed Plasma Concentration (Cmax) of GDC-9545 | Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days) | The pharmacokinetics (PK) parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin. The PK parameters Cmax, AUC0-t, and AUC0-∞ for GDC-9545 were analyzed to evaluate the relative bioavailability of GDC-9545 as a Phase 3 capsule formulation compared to a Phase 1 tablet formulation under fasted conditions (Treatment B vs. Treatment A) and to assess the food effect on GDC-9545 PK for a Phase 3 capsule formulation (Treatment C vs. Treatment B). The mixed-effect analysis of variance model for three-period crossover design was used for formulation comparison and fasted state and fed state comparison of capsule. The model included sequence, formulation, and period as fixed effects and a random effect for subject within sequence. An unstructured covariance structure was to be used; however, if it failed to converge, an alternative covariance structure may have been applied. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Abnormalities in Clinical Chemistry, Hematology, and Urinalysis Laboratory Tests | Baseline, Days 2 and 8 of Period 1-3, and 12-14 days after last dose (up to 34 days) | Participants provided blood and urine samples at the specified timepoints for laboratory analysis of clinical chemistry, hematology, and urinalysis parameters (please refer to Appendix A of the protocol for a complete list of parameters). Any of the laboratory test results that were outside of the reference range were considered abnormalities. Not every laboratory abnormality qualified as an adverse event (AE). A laboratory test result was reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. All AEs were assigned a severity grade (from 1 to 5) using the NCI-CTCAE v5.0; for AEs not specifically listed in the NCI-CTCAE: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening; and Grade 5 is death related to an AE. |
| Change From Baseline in Systolic Blood Pressure Over Time | Baseline and post-dose on Days 1 to 8 of Periods 1-3 (up to 27 days) | Vital signs (including oral temperature, respiratory rate, and supine blood pressure and pulse rate) were obtained at the specified timepoints. Supine blood pressure was obtained after the participant had been supine for at least 5 minutes. When vital signs were scheduled at the same time as blood draws, the blood draws were obtained at the scheduled timepoint, and the vital signs were obtained as close to the scheduled blood draw as possible, but prior to the blood draw. The baseline value was defined as the last value recorded prior to the first dose in each treatment period. The normal reference range for supine systolic blood pressure was 90-140 millimetres of mercury (mmHg). |
| Change From Baseline in Diastolic Blood Pressure Over Time | Baseline and Days 1 to 8 of Periods 1-3 (up to 27 days) | Vital signs (including oral temperature, respiratory rate, and supine blood pressure and pulse rate) were obtained at the specified timepoints. Supine blood pressure was obtained after the participant had been supine for at least 5 minutes. When vital signs were scheduled at the same time as blood draws, the blood draws were obtained at the scheduled timepoint, and the vital signs were obtained as close to the scheduled blood draw as possible, but prior to the blood draw. The baseline value was defined as the last value recorded prior to the first dose in each treatment period. The normal reference range for supine diastolic blood pressure was 50-90 mmHg. |
| Change From Baseline in Pulse Rate Over Time | Baseline and Days 1 to 8 of Periods 1-3 (up to 27 days) | Vital signs (including oral temperature, respiratory rate, and supine blood pressure and pulse rate) were obtained at the specified timepoints. Supine pulse rate was obtained after the participant had been supine for at least 5 minutes. When vital signs were scheduled at the same time as blood draws, the blood draws were obtained at the scheduled timepoint, and the vital signs were obtained as close to the scheduled blood draw as possible, but prior to the blood draw. The baseline value was defined as the last value recorded prior to the first dose in each treatment period. The normal reference range for supine pulse rate was 40-100 beats per minute. |
| Change From Baseline in Respiratory Rate Over Time | Baseline and Days 1 to 8 of Periods 1-3 (up to 27 days) | Vital signs (including oral temperature, respiratory rate, and supine blood pressure and pulse rate) were obtained at the specified timepoints. When vital signs were scheduled at the same time as blood draws, the blood draws were obtained at the scheduled timepoint, and the vital signs were obtained as close to the scheduled blood draw as possible, but prior to the blood draw. The baseline value was defined as the last value recorded prior to the first dose in each treatment period. The normal reference range for respiratory rate was 10-24 breaths per minute. |
| Change From Baseline in Oral Body Temperature Over Time | Baseline and Days 1 to 8 of Periods 1-3 (up to 27 days) | Vital signs (including oral temperature, respiratory rate, and supine blood pressure and pulse rate) were obtained at the specified timepoints. When vital signs were scheduled at the same time as blood draws, the blood draws were obtained at the scheduled timepoint, and the vital signs were obtained as close to the scheduled blood draw as possible, but prior to the blood draw. The baseline value was defined as the last value recorded prior to the first dose in each treatment period. The normal reference range for oral body temperature was 35.5-37.8 degrees Celsius (C). |
| Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | Baseline, and pre-dose and 4 hours post-dose on Day 1, and post-dose on Days 2, and 8 of Periods 1-3 (up to 27 days) | A single 12-lead electrocardiogram (ECG) was obtained at the specified timepoints. To minimize variability in autonomic tone and heart rate, participants rested quietly and in a supine position for at least 5 minutes prior to recording the ECG. Blood draws, other procedures, activity, and environmental distractions (e.g., television, radio, conversation) were to be avoided during the pre-ECG resting period and between ECG recordings to minimize variability due to the effects of activity and stress on cardiac electrophysiology. Whenever possible, ECG tracings for each participant were to be obtained from the same type of machine throughout the study. The baseline value was defined as the last value recorded prior to the first dose in each treatment period. The following are the normal reference ranges for ECG interval durations in milliseconds (msec): PR \[120-210 msec\]; QRS \[upper limit: \<120 msec\]; QT, QTcB, and QTcF \[upper limit: \<470 msec\]. |
| Change From Baseline in Heart Rate Over Time, as Measured by Electrocardiogram | Baseline, and post-dose on Days 1, 2, and 8 of Periods 1-3 (up to 27 days) | A single 12-lead electrocardiogram (ECG) was obtained at the specified timepoints. To minimize variability in autonomic tone and heart rate, participants rested quietly and in a supine position for at least 5 minutes prior to recording the ECG. Blood draws, other procedures, activity, and environmental distractions (e.g., television, radio, conversation) were to be avoided during the pre-ECG resting period and between ECG recordings to minimize variability due to the effects of activity and stress on cardiac electrophysiology. Whenever possible, ECG tracings for each participant were to be obtained from the same type of machine throughout the study. The baseline value was defined as the last value recorded prior to the first dose in each treatment period. The normal reference range for heart rate was 50-100 beats per minute. |
| Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | From first dose of study drug until 14 days after the last dose of study drug (up to 41 days) | The investigator sought information on adverse events (AEs) at each contact with a participant. All AEs, whether reported by the participant or noted by study personnel, were recorded. All AEs were assigned a severity grade (from 1 to 5) using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0). Severity refers to the intensity of an AE. The following is the severity grading scale used for AEs that are not specifically listed in the NCI-CTCAE: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening; and Grade 5 is death related to an AE. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GDC-9545 Treatment Sequence A, B, and C Participants randomized to this arm received one dose of GDC-9545 at the start (Day 1) of each of three treatment periods according to the treatment cross-over sequence A, B, and C (please refer to the intervention descriptions). The washout period between doses was a minimum of 10 days. | 3 |
| GDC-9545 Treatment Sequence B, C, and A Participants randomized to this arm received one dose of GDC-9545 at the start (Day 1) of each of three treatment periods according to the treatment cross-over sequence B, C, and A (please refer to the intervention descriptions). The washout period between doses was a minimum of 10 days. | 3 |
| GDC-9545 Treatment Sequence C, A, and B Participants randomized to this arm received one dose of GDC-9545 at the start (Day 1) of each of three treatment periods according to the treatment cross-over sequence C, A, and B (please refer to the intervention descriptions). The washout period between doses was a minimum of 10 days. | 3 |
| GDC-9545 Treatment Sequence A, C, and B Participants randomized to this arm received one dose of GDC-9545 at the start (Day 1) of each of three treatment periods according to the treatment cross-over sequence A, C, and B (please refer to the intervention descriptions). The washout period between doses was a minimum of 10 days. | 3 |
| GDC-9545 Treatment Sequence B, A, and C Participants randomized to this arm received one dose of GDC-9545 at the start (Day 1) of each of three treatment periods according to the treatment cross-over sequence B, A, and C (please refer to the intervention descriptions). The washout period between doses was a minimum of 10 days. | 3 |
| GDC-9545 Treatment Sequence C, B, and A Participants randomized to this arm received one dose of GDC-9545 at the start (Day 1) of each of three treatment periods according to the treatment cross-over sequence C, B, and A (please refer to the intervention descriptions). The washout period between doses will be a minimum of 10 days. | 3 |
| Total | 18 |
Baseline characteristics
| Characteristic | GDC-9545 Treatment Sequence A, B, and C | GDC-9545 Treatment Sequence B, C, and A | GDC-9545 Treatment Sequence C, A, and B | GDC-9545 Treatment Sequence A, C, and B | GDC-9545 Treatment Sequence B, A, and C | GDC-9545 Treatment Sequence C, B, and A | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 51.0 Years STANDARD_DEVIATION 4.4 | 55.0 Years STANDARD_DEVIATION 5.2 | 48.3 Years STANDARD_DEVIATION 8.1 | 54.0 Years STANDARD_DEVIATION 9.5 | 56.3 Years STANDARD_DEVIATION 5.9 | 53.7 Years STANDARD_DEVIATION 4.9 | 53.1 Years STANDARD_DEVIATION 6.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 3 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 18 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 18 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 2 / 18 | 2 / 18 | 3 / 18 | 5 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 |
Outcome results
Primary
Apparent Terminal Elimination Half-Life (t1/2) of GDC-9545
The pharmacokinetics parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin.
Time frame: Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days)
Population: Pharmacokinetics (PK) Population: all participants who received at least one dose of study drug and had at least one evaluable postdose PK sample, with participants grouped according to the treatment received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GDC-9545 Tablet, Fasted: Treatment A | Apparent Terminal Elimination Half-Life (t1/2) of GDC-9545 | 35.4 Hours | Geometric Coefficient of Variation 15.7 |
| GDC-9545 Capsule, Fasted: Treatment B | Apparent Terminal Elimination Half-Life (t1/2) of GDC-9545 | 37.4 Hours | Geometric Coefficient of Variation 15.5 |
| GDC-9545 Capsule, Fed: Treatment C | Apparent Terminal Elimination Half-Life (t1/2) of GDC-9545 | 36.9 Hours | Geometric Coefficient of Variation 14.4 |
Primary
Apparent Terminal Elimination Rate Constant (λz) of GDC-9545
The pharmacokinetics parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin. The apparent terminal elimination rate constant (λz) is the magnitude of the slope of the linear regression of the log concentration versus time profile during the terminal phase.
Time frame: Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days)
Population: Pharmacokinetics (PK) Population: all participants who received at least one dose of study drug and had at least one evaluable postdose PK sample, with participants grouped according to the treatment received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GDC-9545 Tablet, Fasted: Treatment A | Apparent Terminal Elimination Rate Constant (λz) of GDC-9545 | 0.0196 Elimination rate per hour (/h) | Geometric Coefficient of Variation 15.7 |
| GDC-9545 Capsule, Fasted: Treatment B | Apparent Terminal Elimination Rate Constant (λz) of GDC-9545 | 0.0185 Elimination rate per hour (/h) | Geometric Coefficient of Variation 15.5 |
| GDC-9545 Capsule, Fed: Treatment C | Apparent Terminal Elimination Rate Constant (λz) of GDC-9545 | 0.0188 Elimination rate per hour (/h) | Geometric Coefficient of Variation 14.4 |
Primary
Apparent Total Clearance (CL/F) of GDC-9545
The pharmacokinetics parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin.
Time frame: Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days)
Population: Pharmacokinetics (PK) Population: all participants who received at least one dose of study drug and had at least one evaluable postdose PK sample, with participants grouped according to the treatment received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GDC-9545 Tablet, Fasted: Treatment A | Apparent Total Clearance (CL/F) of GDC-9545 | 7.76 Litres per hour (L/h) | Geometric Coefficient of Variation 32.6 |
| GDC-9545 Capsule, Fasted: Treatment B | Apparent Total Clearance (CL/F) of GDC-9545 | 7.97 Litres per hour (L/h) | Geometric Coefficient of Variation 30.8 |
| GDC-9545 Capsule, Fed: Treatment C | Apparent Total Clearance (CL/F) of GDC-9545 | 8.68 Litres per hour (L/h) | Geometric Coefficient of Variation 28.1 |
Primary
Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of GDC-9545
The pharmacokinetics parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin.
Time frame: Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days)
Population: Pharmacokinetics (PK) Population: all participants who received at least one dose of study drug and had at least one evaluable postdose PK sample, with participants grouped according to the treatment received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GDC-9545 Tablet, Fasted: Treatment A | Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of GDC-9545 | 397 Litres (L) | Geometric Coefficient of Variation 29.8 |
| GDC-9545 Capsule, Fasted: Treatment B | Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of GDC-9545 | 430 Litres (L) | Geometric Coefficient of Variation 26.5 |
| GDC-9545 Capsule, Fed: Treatment C | Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of GDC-9545 | 462 Litres (L) | Geometric Coefficient of Variation 29.8 |
Primary
Area Under the Plasma Concentration-Time Curve From Hour 0 Extrapolated to Infinity (AUC0-∞) of GDC-9545
The pharmacokinetics (PK) parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin. The PK parameters Cmax, AUC0-t, and AUC0-∞ for GDC-9545 were analyzed to evaluate the relative bioavailability of GDC-9545 as a Phase 3 capsule formulation compared to a Phase 1 tablet formulation under fasted conditions (Treatment B vs. Treatment A) and to assess the food effect on GDC-9545 PK for a Phase 3 capsule formulation (Treatment C vs. Treatment B). The mixed-effect analysis of variance model for three-period crossover design was used for formulation comparison and fasted state and fed state comparison of capsule. The model included sequence, formulation, and period as fixed effects and a random effect for subject within sequence. An unstructured covariance structure was to be used; however, if it failed to converge, an alternative covariance structure may have been applied.
Time frame: Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days)
Population: Pharmacokinetics (PK) Population: all participants who received at least one dose of study drug and had at least one evaluable postdose PK sample, with participants grouped according to the treatment received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GDC-9545 Tablet, Fasted: Treatment A | Area Under the Plasma Concentration-Time Curve From Hour 0 Extrapolated to Infinity (AUC0-∞) of GDC-9545 | 3860 Hours*ng/mL | Geometric Coefficient of Variation 32.6 |
| GDC-9545 Capsule, Fasted: Treatment B | Area Under the Plasma Concentration-Time Curve From Hour 0 Extrapolated to Infinity (AUC0-∞) of GDC-9545 | 3770 Hours*ng/mL | Geometric Coefficient of Variation 30.8 |
| GDC-9545 Capsule, Fed: Treatment C | Area Under the Plasma Concentration-Time Curve From Hour 0 Extrapolated to Infinity (AUC0-∞) of GDC-9545 | 3460 Hours*ng/mL | Geometric Coefficient of Variation 28.1 |
Comparison: The sample size chosen for this study was based upon precedent set by other PK studies of similar nature and was not based on power calculations.90% CI: [0.908, 1.05]
Comparison: The sample size chosen for this study was based upon precedent set by other PK studies of similar nature and was not based on power calculations.90% CI: [0.856, 0.985]
Primary
Area Under the Plasma Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of GDC-9545
The pharmacokinetics (PK) parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin. The PK parameters Cmax, AUC0-t, and AUC0-∞ for GDC-9545 were analyzed to evaluate the relative bioavailability of GDC-9545 as a Phase 3 capsule formulation compared to a Phase 1 tablet formulation under fasted conditions (Treatment B vs. Treatment A) and to assess the food effect on GDC-9545 PK for a Phase 3 capsule formulation (Treatment C vs. Treatment B). The mixed-effect analysis of variance model for three-period crossover design was used for formulation comparison and fasted state and fed state comparison of capsule. The model included sequence, formulation, and period as fixed effects and a random effect for subject within sequence. An unstructured covariance structure was to be used; however, if it failed to converge, an alternative covariance structure may have been applied.
Time frame: Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days)
Population: Pharmacokinetics (PK) Population: all participants who received at least one dose of study drug and had at least one evaluable postdose PK sample, with participants grouped according to the treatment received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GDC-9545 Tablet, Fasted: Treatment A | Area Under the Plasma Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of GDC-9545 | 3710 Hours*ng/mL | Geometric Coefficient of Variation 31.8 |
| GDC-9545 Capsule, Fasted: Treatment B | Area Under the Plasma Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of GDC-9545 | 3600 Hours*ng/mL | Geometric Coefficient of Variation 29.8 |
| GDC-9545 Capsule, Fed: Treatment C | Area Under the Plasma Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of GDC-9545 | 3310 Hours*ng/mL | Geometric Coefficient of Variation 27.6 |
Comparison: The sample size chosen for this study was based upon precedent set by other PK studies of similar nature and was not based on power calculations.90% CI: [0.903, 1.04]
Comparison: The sample size chosen for this study was based upon precedent set by other PK studies of similar nature and was not based on power calculations.90% CI: [0.855, 0.988]
Primary
Maximum Observed Plasma Concentration (Cmax) of GDC-9545
The pharmacokinetics (PK) parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin. The PK parameters Cmax, AUC0-t, and AUC0-∞ for GDC-9545 were analyzed to evaluate the relative bioavailability of GDC-9545 as a Phase 3 capsule formulation compared to a Phase 1 tablet formulation under fasted conditions (Treatment B vs. Treatment A) and to assess the food effect on GDC-9545 PK for a Phase 3 capsule formulation (Treatment C vs. Treatment B). The mixed-effect analysis of variance model for three-period crossover design was used for formulation comparison and fasted state and fed state comparison of capsule. The model included sequence, formulation, and period as fixed effects and a random effect for subject within sequence. An unstructured covariance structure was to be used; however, if it failed to converge, an alternative covariance structure may have been applied.
Time frame: Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days)
Population: Pharmacokinetics (PK) Population: all participants who received at least one dose of study drug and had at least one evaluable postdose PK sample, with participants grouped according to the treatment received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GDC-9545 Tablet, Fasted: Treatment A | Maximum Observed Plasma Concentration (Cmax) of GDC-9545 | 126 nanograms per millilitre (ng/mL) | Geometric Coefficient of Variation 29.6 |
| GDC-9545 Capsule, Fasted: Treatment B | Maximum Observed Plasma Concentration (Cmax) of GDC-9545 | 129 nanograms per millilitre (ng/mL) | Geometric Coefficient of Variation 27.7 |
| GDC-9545 Capsule, Fed: Treatment C | Maximum Observed Plasma Concentration (Cmax) of GDC-9545 | 102 nanograms per millilitre (ng/mL) | Geometric Coefficient of Variation 27.3 |
Comparison: The sample size chosen for this study was based upon precedent set by other PK studies of similar nature and was not based on power calculations.90% CI: [0.945, 1.12]
Comparison: The sample size chosen for this study was based upon precedent set by other PK studies of similar nature and was not based on power calculations.90% CI: [0.726, 0.859]
Primary
Percentage of Area Under the Plasma Concentration-Time Curve (AUC) That is Due to Extrapolation From Last Measurable Concentration to Infinity (%AUCextrap) of GDC-9545
The pharmacokinetics parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin.
Time frame: Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days)
Population: Pharmacokinetics (PK) Population: all participants who received at least one dose of study drug and had at least one evaluable postdose PK sample, with participants grouped according to the treatment received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GDC-9545 Tablet, Fasted: Treatment A | Percentage of Area Under the Plasma Concentration-Time Curve (AUC) That is Due to Extrapolation From Last Measurable Concentration to Infinity (%AUCextrap) of GDC-9545 | 3.40 Percentage of AUC | Geometric Coefficient of Variation 58.5 |
| GDC-9545 Capsule, Fasted: Treatment B | Percentage of Area Under the Plasma Concentration-Time Curve (AUC) That is Due to Extrapolation From Last Measurable Concentration to Infinity (%AUCextrap) of GDC-9545 | 3.87 Percentage of AUC | Geometric Coefficient of Variation 49.8 |
| GDC-9545 Capsule, Fed: Treatment C | Percentage of Area Under the Plasma Concentration-Time Curve (AUC) That is Due to Extrapolation From Last Measurable Concentration to Infinity (%AUCextrap) of GDC-9545 | 3.78 Percentage of AUC | Geometric Coefficient of Variation 48.9 |
Primary
Time of Last Quantifiable Plasma Concentration (Tlast) of GDC-9545
The pharmacokinetics parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin.
Time frame: Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days)
Population: Pharmacokinetics (PK) Population: all participants who received at least one dose of study drug and had at least one evaluable postdose PK sample, with participants grouped according to the treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GDC-9545 Tablet, Fasted: Treatment A | Time of Last Quantifiable Plasma Concentration (Tlast) of GDC-9545 | 168 Hours |
| GDC-9545 Capsule, Fasted: Treatment B | Time of Last Quantifiable Plasma Concentration (Tlast) of GDC-9545 | 168 Hours |
| GDC-9545 Capsule, Fed: Treatment C | Time of Last Quantifiable Plasma Concentration (Tlast) of GDC-9545 | 168 Hours |
Primary
Time to First Quantifiable Plasma Concentration (Tlag) of GDC-9545
The pharmacokinetics parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin.
Time frame: Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days)
Population: Pharmacokinetics (PK) Population: all participants who received at least one dose of study drug and had at least one evaluable postdose PK sample, with participants grouped according to the treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GDC-9545 Tablet, Fasted: Treatment A | Time to First Quantifiable Plasma Concentration (Tlag) of GDC-9545 | 0 Hours |
| GDC-9545 Capsule, Fasted: Treatment B | Time to First Quantifiable Plasma Concentration (Tlag) of GDC-9545 | 0 Hours |
| GDC-9545 Capsule, Fed: Treatment C | Time to First Quantifiable Plasma Concentration (Tlag) of GDC-9545 | 0 Hours |
Primary
Time to Maximum Observed Plasma Concentration (Tmax) of GDC-9545
The pharmacokinetics (PK) parameters were determined where possible from the plasma concentrations of GDC-9545 using non-compartmental methods performed using Phoenix WinNonlin. The parameter tmax was analyzed nonparametrically using the Wilcoxon signed-rank test. The median difference between the test and reference investigational products (GDC-9545 Phase 3 capsule formulation compared to a Phase 1 tablet formulation under fasted conditions \[Treatment B vs. Treatment A\] and the food effect on GDC-9545 PK for a Phase 3 capsule formulation \[Treatment C vs. Treatment B\]) and the corresponding 90% confidence interval were calculated.
Time frame: Pre-dose (0 hour) and post-dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours on Day 1 and post-dose once a day on Days 2 to 8 of Periods 1-3 (up to 27 days)
Population: Pharmacokinetics (PK) Population: all participants who received at least one dose of study drug and had at least one evaluable postdose PK sample, with participants grouped according to the treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GDC-9545 Tablet, Fasted: Treatment A | Time to Maximum Observed Plasma Concentration (Tmax) of GDC-9545 | 2.25 Hours |
| GDC-9545 Capsule, Fasted: Treatment B | Time to Maximum Observed Plasma Concentration (Tmax) of GDC-9545 | 2.28 Hours |
| GDC-9545 Capsule, Fed: Treatment C | Time to Maximum Observed Plasma Concentration (Tmax) of GDC-9545 | 5.00 Hours |
Comparison: The sample size chosen for this study was based upon precedent set by other PK studies of similar nature and was not based on power calculations.90% CI: [-0.225, 1.5]
Comparison: The sample size chosen for this study was based upon precedent set by other PK studies of similar nature and was not based on power calculations.90% CI: [1.26, 2.45]
Secondary
Change From Baseline in Diastolic Blood Pressure Over Time
Vital signs (including oral temperature, respiratory rate, and supine blood pressure and pulse rate) were obtained at the specified timepoints. Supine blood pressure was obtained after the participant had been supine for at least 5 minutes. When vital signs were scheduled at the same time as blood draws, the blood draws were obtained at the scheduled timepoint, and the vital signs were obtained as close to the scheduled blood draw as possible, but prior to the blood draw. The baseline value was defined as the last value recorded prior to the first dose in each treatment period. The normal reference range for supine diastolic blood pressure was 50-90 mmHg.
Time frame: Baseline and Days 1 to 8 of Periods 1-3 (up to 27 days)
Population: Safety Population: all participants who received at least one dose of study drug, with participants grouped according to the treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 3 | -4.2 millimetres of mercury (mmHg) | Standard Deviation 6.96 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 8 | -3.1 millimetres of mercury (mmHg) | Standard Deviation 6.66 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 5 | -2.8 millimetres of mercury (mmHg) | Standard Deviation 7.36 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 4 | -2.3 millimetres of mercury (mmHg) | Standard Deviation 4.67 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Diastolic Blood Pressure Over Time | Baseline (BL) - Value at Visit | 64.2 millimetres of mercury (mmHg) | Standard Deviation 7.86 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 7 | -3.1 millimetres of mercury (mmHg) | Standard Deviation 7.07 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 2 | -3.2 millimetres of mercury (mmHg) | Standard Deviation 6.13 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 1 | -2.8 millimetres of mercury (mmHg) | Standard Deviation 5.31 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 6 | -4.3 millimetres of mercury (mmHg) | Standard Deviation 6.13 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 4 | -2.3 millimetres of mercury (mmHg) | Standard Deviation 7.5 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Diastolic Blood Pressure Over Time | Baseline (BL) - Value at Visit | 62.5 millimetres of mercury (mmHg) | Standard Deviation 8.4 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 1 | -3.1 millimetres of mercury (mmHg) | Standard Deviation 6.73 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 2 | -2.7 millimetres of mercury (mmHg) | Standard Deviation 8.73 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 3 | 0.2 millimetres of mercury (mmHg) | Standard Deviation 7.52 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 5 | -0.9 millimetres of mercury (mmHg) | Standard Deviation 5.31 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 6 | -1.8 millimetres of mercury (mmHg) | Standard Deviation 6.37 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 7 | -0.9 millimetres of mercury (mmHg) | Standard Deviation 6.1 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 8 | 0.1 millimetres of mercury (mmHg) | Standard Deviation 7.45 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 2 | -1.6 millimetres of mercury (mmHg) | Standard Deviation 6.64 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Diastolic Blood Pressure Over Time | Baseline (BL) - Value at Visit | 62.8 millimetres of mercury (mmHg) | Standard Deviation 7.67 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 6 | -0.4 millimetres of mercury (mmHg) | Standard Deviation 7.22 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 1 | -3.3 millimetres of mercury (mmHg) | Standard Deviation 6.23 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 8 | -3.3 millimetres of mercury (mmHg) | Standard Deviation 7.39 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 4 | -2.3 millimetres of mercury (mmHg) | Standard Deviation 6.44 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 3 | -1.0 millimetres of mercury (mmHg) | Standard Deviation 6.87 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 7 | -1.8 millimetres of mercury (mmHg) | Standard Deviation 6.83 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Diastolic Blood Pressure Over Time | Change from BL at Day 5 | -2.3 millimetres of mercury (mmHg) | Standard Deviation 6.82 |
Secondary
Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram
A single 12-lead electrocardiogram (ECG) was obtained at the specified timepoints. To minimize variability in autonomic tone and heart rate, participants rested quietly and in a supine position for at least 5 minutes prior to recording the ECG. Blood draws, other procedures, activity, and environmental distractions (e.g., television, radio, conversation) were to be avoided during the pre-ECG resting period and between ECG recordings to minimize variability due to the effects of activity and stress on cardiac electrophysiology. Whenever possible, ECG tracings for each participant were to be obtained from the same type of machine throughout the study. The baseline value was defined as the last value recorded prior to the first dose in each treatment period. The following are the normal reference ranges for ECG interval durations in milliseconds (msec): PR \[120-210 msec\]; QRS \[upper limit: \<120 msec\]; QT, QTcB, and QTcF \[upper limit: \<470 msec\].
Time frame: Baseline, and pre-dose and 4 hours post-dose on Day 1, and post-dose on Days 2, and 8 of Periods 1-3 (up to 27 days)
Population: Safety Population: all participants who received at least one dose of study drug, with participants grouped according to the treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | RR: Change from BL at Day 2 | 19.6 milliseconds (msec) | Standard Deviation 88.42 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | PR: Change from BL at Day 1 | -3.6 milliseconds (msec) | Standard Deviation 5.8 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | PR: Change from BL at Day 2 | -3.9 milliseconds (msec) | Standard Deviation 10.65 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | PR: Change from BL at Day 8 | -2.1 milliseconds (msec) | Standard Deviation 9.32 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | RR: Baseline (BL) - Value at Visit | 966.7 milliseconds (msec) | Standard Deviation 115.12 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | RR: Change from BL at Day 1 | 43.9 milliseconds (msec) | Standard Deviation 64.1 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | PR: Baseline (BL) - Value at Visit | 170.2 milliseconds (msec) | Standard Deviation 15.38 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | RR: Change from BL at Day 8 | -1.3 milliseconds (msec) | Standard Deviation 74.84 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QRS: Baseline (BL) - Value at Visit | 87.4 milliseconds (msec) | Standard Deviation 8.79 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QRS: Change from BL at Day 1 | -0.1 milliseconds (msec) | Standard Deviation 5.01 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QRS: Change from BL at Day 2 | 0.7 milliseconds (msec) | Standard Deviation 5.01 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QRS: Change from BL at Day 8 | -0.6 milliseconds (msec) | Standard Deviation 5.18 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QT: Baseline (BL) - Value at Visit | 414.7 milliseconds (msec) | Standard Deviation 21.01 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QT: Change from BL at Day 1 | 5.9 milliseconds (msec) | Standard Deviation 11.93 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QT: Change from BL at Day 2 | 0.5 milliseconds (msec) | Standard Deviation 16.45 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QT: Change from BL at Day 8 | -2.6 milliseconds (msec) | Standard Deviation 11.78 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcB: Baseline (BL) - Value at Visit | 422.3 milliseconds (msec) | Standard Deviation 12.45 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcB: Change from BL at Day 1 | -3.3 milliseconds (msec) | Standard Deviation 12.28 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcB: Change from BL at Day 2 | -3.4 milliseconds (msec) | Standard Deviation 11.72 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcB: Change from BL at Day 8 | -2.4 milliseconds (msec) | Standard Deviation 12.46 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcF: Baseline (BL) - Value at Visit | 419.5 milliseconds (msec) | Standard Deviation 11.1 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcF: Change from BL at Day 1 | -0.2 milliseconds (msec) | Standard Deviation 10.38 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcF: Change from BL at Day 2 | -2.1 milliseconds (msec) | Standard Deviation 10.4 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcF: Change from BL at Day 8 | -2.7 milliseconds (msec) | Standard Deviation 9.54 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcF: Change from BL at Day 1 | 2.8 milliseconds (msec) | Standard Deviation 8.5 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | PR: Baseline (BL) - Value at Visit | 171.5 milliseconds (msec) | Standard Deviation 13.87 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QT: Baseline (BL) - Value at Visit | 416.5 milliseconds (msec) | Standard Deviation 18.51 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcB: Baseline (BL) - Value at Visit | 419.9 milliseconds (msec) | Standard Deviation 15.4 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | PR: Change from BL at Day 1 | -6.1 milliseconds (msec) | Standard Deviation 7.37 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QRS: Change from BL at Day 2 | -0.7 milliseconds (msec) | Standard Deviation 5.28 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcF: Baseline (BL) - Value at Visit | 418.3 milliseconds (msec) | Standard Deviation 12.85 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | PR: Change from BL at Day 2 | -4.8 milliseconds (msec) | Standard Deviation 11.93 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QT: Change from BL at Day 1 | 11.4 milliseconds (msec) | Standard Deviation 15.44 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcF: Change from BL at Day 2 | -1.6 milliseconds (msec) | Standard Deviation 8.82 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | PR: Change from BL at Day 8 | -4.4 milliseconds (msec) | Standard Deviation 9.43 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QRS: Change from BL at Day 1 | 0.6 milliseconds (msec) | Standard Deviation 3.66 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcB: Change from BL at Day 1 | -1.7 milliseconds (msec) | Standard Deviation 12.72 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | RR: Baseline (BL) - Value at Visit | 986.8 milliseconds (msec) | Standard Deviation 106.4 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QT: Change from BL at Day 2 | 5.7 milliseconds (msec) | Standard Deviation 16.12 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QRS: Change from BL at Day 8 | -1.5 milliseconds (msec) | Standard Deviation 4.93 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | RR: Change from BL at Day 1 | 64.6 milliseconds (msec) | Standard Deviation 113.36 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QRS: Baseline (BL) - Value at Visit | 88.9 milliseconds (msec) | Standard Deviation 7.59 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcF: Change from BL at Day 8 | -1.0 milliseconds (msec) | Standard Deviation 9.11 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | RR: Change from BL at Day 2 | 55.0 milliseconds (msec) | Standard Deviation 97.58 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QT: Change from BL at Day 8 | -2.8 milliseconds (msec) | Standard Deviation 10.71 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcB: Change from BL at Day 2 | -5.4 milliseconds (msec) | Standard Deviation 10.99 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | RR: Change from BL at Day 8 | -12.6 milliseconds (msec) | Standard Deviation 71.04 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcB: Change from BL at Day 8 | -0.2 milliseconds (msec) | Standard Deviation 11.9 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | RR: Change from BL at Day 8 | 9.9 milliseconds (msec) | Standard Deviation 89.01 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QRS: Baseline (BL) - Value at Visit | 89.4 milliseconds (msec) | Standard Deviation 8.93 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QRS: Change from BL at Day 1 | -4.4 milliseconds (msec) | Standard Deviation 8.65 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QRS: Change from BL at Day 2 | -2.1 milliseconds (msec) | Standard Deviation 5.78 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcB: Change from BL at Day 8 | -0.6 milliseconds (msec) | Standard Deviation 10.54 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QRS: Change from BL at Day 8 | -1.7 milliseconds (msec) | Standard Deviation 4.36 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcF: Change from BL at Day 2 | 2.8 milliseconds (msec) | Standard Deviation 9.58 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QT: Baseline (BL) - Value at Visit | 411.9 milliseconds (msec) | Standard Deviation 25.22 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QT: Change from BL at Day 1 | -9.7 milliseconds (msec) | Standard Deviation 18.23 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcF: Baseline (BL) - Value at Visit | 415.9 milliseconds (msec) | Standard Deviation 11.91 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QT: Change from BL at Day 2 | 11.9 milliseconds (msec) | Standard Deviation 13.27 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcF: Change from BL at Day 8 | 0.1 milliseconds (msec) | Standard Deviation 8.51 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QT: Change from BL at Day 8 | 1.6 milliseconds (msec) | Standard Deviation 15.15 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | PR: Baseline (BL) - Value at Visit | 165.8 milliseconds (msec) | Standard Deviation 17.39 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | PR: Change from BL at Day 1 | -2.7 milliseconds (msec) | Standard Deviation 13.46 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcB: Baseline (BL) - Value at Visit | 418.7 milliseconds (msec) | Standard Deviation 12.68 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | PR: Change from BL at Day 2 | 4.4 milliseconds (msec) | Standard Deviation 8.32 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcF: Change from BL at Day 1 | -8.5 milliseconds (msec) | Standard Deviation 12.22 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | PR: Change from BL at Day 8 | -1.0 milliseconds (msec) | Standard Deviation 10.58 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | RR: Baseline (BL) - Value at Visit | 971.6 milliseconds (msec) | Standard Deviation 131.35 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcB: Change from BL at Day 1 | -7.9 milliseconds (msec) | Standard Deviation 17.39 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | RR: Change from BL at Day 1 | -6.0 milliseconds (msec) | Standard Deviation 134.23 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | RR: Change from BL at Day 2 | 66.7 milliseconds (msec) | Standard Deviation 89.61 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram | QTcB: Change from BL at Day 2 | -2.1 milliseconds (msec) | Standard Deviation 12.89 |
Secondary
Change From Baseline in Heart Rate Over Time, as Measured by Electrocardiogram
A single 12-lead electrocardiogram (ECG) was obtained at the specified timepoints. To minimize variability in autonomic tone and heart rate, participants rested quietly and in a supine position for at least 5 minutes prior to recording the ECG. Blood draws, other procedures, activity, and environmental distractions (e.g., television, radio, conversation) were to be avoided during the pre-ECG resting period and between ECG recordings to minimize variability due to the effects of activity and stress on cardiac electrophysiology. Whenever possible, ECG tracings for each participant were to be obtained from the same type of machine throughout the study. The baseline value was defined as the last value recorded prior to the first dose in each treatment period. The normal reference range for heart rate was 50-100 beats per minute.
Time frame: Baseline, and post-dose on Days 1, 2, and 8 of Periods 1-3 (up to 27 days)
Population: Safety Population: all participants who received at least one dose of study drug, grouped according to the treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Heart Rate Over Time, as Measured by Electrocardiogram | Baseline (BL) - Value at Visit | 62.3 Beats per minute | Standard Deviation 6.96 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Heart Rate Over Time, as Measured by Electrocardiogram | Change from BL at Day 1 | -2.9 Beats per minute | Standard Deviation 3.89 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Heart Rate Over Time, as Measured by Electrocardiogram | Change from BL at Day 2 | -1.0 Beats per minute | Standard Deviation 5.92 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Heart Rate Over Time, as Measured by Electrocardiogram | Change from BL at Day 8 | -0.2 Beats per minute | Standard Deviation 5.31 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Heart Rate Over Time, as Measured by Electrocardiogram | Change from BL at Day 8 | 0.8 Beats per minute | Standard Deviation 4.71 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Heart Rate Over Time, as Measured by Electrocardiogram | Baseline (BL) - Value at Visit | 61.2 Beats per minute | Standard Deviation 6.71 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Heart Rate Over Time, as Measured by Electrocardiogram | Change from BL at Day 2 | -3.4 Beats per minute | Standard Deviation 6.03 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Heart Rate Over Time, as Measured by Electrocardiogram | Change from BL at Day 1 | -4.1 Beats per minute | Standard Deviation 6.53 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Heart Rate Over Time, as Measured by Electrocardiogram | Change from BL at Day 8 | -0.9 Beats per minute | Standard Deviation 6.35 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Heart Rate Over Time, as Measured by Electrocardiogram | Change from BL at Day 1 | 0.5 Beats per minute | Standard Deviation 8.36 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Heart Rate Over Time, as Measured by Electrocardiogram | Change from BL at Day 2 | -4.6 Beats per minute | Standard Deviation 6.48 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Heart Rate Over Time, as Measured by Electrocardiogram | Baseline (BL) - Value at Visit | 62.4 Beats per minute | Standard Deviation 9.62 |
Secondary
Change From Baseline in Oral Body Temperature Over Time
Vital signs (including oral temperature, respiratory rate, and supine blood pressure and pulse rate) were obtained at the specified timepoints. When vital signs were scheduled at the same time as blood draws, the blood draws were obtained at the scheduled timepoint, and the vital signs were obtained as close to the scheduled blood draw as possible, but prior to the blood draw. The baseline value was defined as the last value recorded prior to the first dose in each treatment period. The normal reference range for oral body temperature was 35.5-37.8 degrees Celsius (C).
Time frame: Baseline and Days 1 to 8 of Periods 1-3 (up to 27 days)
Population: Safety Population: all participants who received at least one dose of study drug, with participants grouped according to the treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 3 | 0.12 degrees Celsius (C) | Standard Deviation 0.14 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 8 | 0.12 degrees Celsius (C) | Standard Deviation 0.202 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 5 | 0.12 degrees Celsius (C) | Standard Deviation 0.163 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 4 | 0.08 degrees Celsius (C) | Standard Deviation 0.182 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Oral Body Temperature Over Time | Baseline (BL) - Value at Visit | 36.65 degrees Celsius (C) | Standard Deviation 0.142 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 7 | 0.08 degrees Celsius (C) | Standard Deviation 0.158 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 2 | 0.12 degrees Celsius (C) | Standard Deviation 0.183 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 1 | 0.06 degrees Celsius (C) | Standard Deviation 0.129 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 6 | 0.08 degrees Celsius (C) | Standard Deviation 0.15 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 4 | 0.09 degrees Celsius (C) | Standard Deviation 0.189 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Oral Body Temperature Over Time | Baseline (BL) - Value at Visit | 36.64 degrees Celsius (C) | Standard Deviation 0.115 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 1 | 0.00 degrees Celsius (C) | Standard Deviation 0.124 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 2 | 0.07 degrees Celsius (C) | Standard Deviation 0.149 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 3 | 0.11 degrees Celsius (C) | Standard Deviation 0.229 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 5 | 0.11 degrees Celsius (C) | Standard Deviation 0.184 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 6 | 0.11 degrees Celsius (C) | Standard Deviation 0.195 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 7 | 0.10 degrees Celsius (C) | Standard Deviation 0.128 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 8 | 0.13 degrees Celsius (C) | Standard Deviation 0.124 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 2 | 0.00 degrees Celsius (C) | Standard Deviation 0.15 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Oral Body Temperature Over Time | Baseline (BL) - Value at Visit | 36.72 degrees Celsius (C) | Standard Deviation 0.129 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 6 | 0.03 degrees Celsius (C) | Standard Deviation 0.137 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 1 | 0.04 degrees Celsius (C) | Standard Deviation 0.195 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 8 | 0.01 degrees Celsius (C) | Standard Deviation 0.135 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 4 | 0.03 degrees Celsius (C) | Standard Deviation 0.146 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 3 | 0.03 degrees Celsius (C) | Standard Deviation 0.119 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 7 | 0.06 degrees Celsius (C) | Standard Deviation 0.138 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Oral Body Temperature Over Time | Change from BL at Day 5 | 0.03 degrees Celsius (C) | Standard Deviation 0.161 |
Secondary
Change From Baseline in Pulse Rate Over Time
Vital signs (including oral temperature, respiratory rate, and supine blood pressure and pulse rate) were obtained at the specified timepoints. Supine pulse rate was obtained after the participant had been supine for at least 5 minutes. When vital signs were scheduled at the same time as blood draws, the blood draws were obtained at the scheduled timepoint, and the vital signs were obtained as close to the scheduled blood draw as possible, but prior to the blood draw. The baseline value was defined as the last value recorded prior to the first dose in each treatment period. The normal reference range for supine pulse rate was 40-100 beats per minute.
Time frame: Baseline and Days 1 to 8 of Periods 1-3 (up to 27 days)
Population: Safety Population: all participants who received at least one dose of study drug, with participants grouped according to the treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 3 | -0.6 Beats per minute | Standard Deviation 5.61 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 8 | 1.1 Beats per minute | Standard Deviation 9 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 5 | -1.1 Beats per minute | Standard Deviation 6.76 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 4 | -1.1 Beats per minute | Standard Deviation 8.08 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Pulse Rate Over Time | Baseline (BL) - Value at Visit | 62.2 Beats per minute | Standard Deviation 7.61 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 7 | -0.7 Beats per minute | Standard Deviation 7.1 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 2 | 1.4 Beats per minute | Standard Deviation 10.34 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 1 | -2.1 Beats per minute | Standard Deviation 6.27 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 6 | -0.2 Beats per minute | Standard Deviation 7.58 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 4 | -2.2 Beats per minute | Standard Deviation 9.52 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Pulse Rate Over Time | Baseline (BL) - Value at Visit | 62.4 Beats per minute | Standard Deviation 8.88 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 1 | -4.1 Beats per minute | Standard Deviation 7.62 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 2 | -3.2 Beats per minute | Standard Deviation 7.65 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 3 | -4.1 Beats per minute | Standard Deviation 6.29 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 5 | -2.8 Beats per minute | Standard Deviation 6.67 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 6 | -0.4 Beats per minute | Standard Deviation 8.6 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 7 | -1.4 Beats per minute | Standard Deviation 5.99 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 8 | -0.1 Beats per minute | Standard Deviation 7.19 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 2 | -5.4 Beats per minute | Standard Deviation 7.01 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Pulse Rate Over Time | Baseline (BL) - Value at Visit | 65.3 Beats per minute | Standard Deviation 11 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 6 | -4.4 Beats per minute | Standard Deviation 8.56 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 1 | -1.3 Beats per minute | Standard Deviation 9.39 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 8 | -2.6 Beats per minute | Standard Deviation 6.3 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 4 | -5.6 Beats per minute | Standard Deviation 7.85 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 3 | -4.8 Beats per minute | Standard Deviation 7.73 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 7 | -5.4 Beats per minute | Standard Deviation 8.2 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Pulse Rate Over Time | Change from BL at Day 5 | -4.7 Beats per minute | Standard Deviation 9.33 |
Secondary
Change From Baseline in Respiratory Rate Over Time
Vital signs (including oral temperature, respiratory rate, and supine blood pressure and pulse rate) were obtained at the specified timepoints. When vital signs were scheduled at the same time as blood draws, the blood draws were obtained at the scheduled timepoint, and the vital signs were obtained as close to the scheduled blood draw as possible, but prior to the blood draw. The baseline value was defined as the last value recorded prior to the first dose in each treatment period. The normal reference range for respiratory rate was 10-24 breaths per minute.
Time frame: Baseline and Days 1 to 8 of Periods 1-3 (up to 27 days)
Population: Safety Population: all participants who received at least one dose of study drug, with participants grouped according to the treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 3 | -0.4 Breaths per minute | Standard Deviation 2.71 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 8 | -0.9 Breaths per minute | Standard Deviation 1.97 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 5 | 0.8 Breaths per minute | Standard Deviation 3.6 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 4 | 0.1 Breaths per minute | Standard Deviation 2 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Respiratory Rate Over Time | Baseline (BL) - Value at Visit | 15.6 Breaths per minute | Standard Deviation 1.76 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 7 | -0.4 Breaths per minute | Standard Deviation 3.26 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 2 | -0.6 Breaths per minute | Standard Deviation 2.9 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 1 | 1.6 Breaths per minute | Standard Deviation 2.53 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 6 | 0.0 Breaths per minute | Standard Deviation 2.74 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 4 | 0.2 Breaths per minute | Standard Deviation 2.54 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Respiratory Rate Over Time | Baseline (BL) - Value at Visit | 15.6 Breaths per minute | Standard Deviation 1.89 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 1 | 1.2 Breaths per minute | Standard Deviation 1.96 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 2 | -0.7 Breaths per minute | Standard Deviation 3.07 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 3 | -0.6 Breaths per minute | Standard Deviation 3.55 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 5 | 0.1 Breaths per minute | Standard Deviation 2.7 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 6 | 0.2 Breaths per minute | Standard Deviation 2.37 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 7 | -1.0 Breaths per minute | Standard Deviation 3.31 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 8 | -1.1 Breaths per minute | Standard Deviation 2.3 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 2 | -0.8 Breaths per minute | Standard Deviation 2.29 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Respiratory Rate Over Time | Baseline (BL) - Value at Visit | 15.6 Breaths per minute | Standard Deviation 2.01 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 6 | -0.6 Breaths per minute | Standard Deviation 3.2 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 1 | 2.0 Breaths per minute | Standard Deviation 3.14 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 8 | -1.0 Breaths per minute | Standard Deviation 2.4 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 4 | -0.3 Breaths per minute | Standard Deviation 2.68 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 3 | -0.6 Breaths per minute | Standard Deviation 3.35 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 7 | -0.8 Breaths per minute | Standard Deviation 3.15 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Respiratory Rate Over Time | Change from BL at Day 5 | 1.0 Breaths per minute | Standard Deviation 2.93 |
Secondary
Change From Baseline in Systolic Blood Pressure Over Time
Vital signs (including oral temperature, respiratory rate, and supine blood pressure and pulse rate) were obtained at the specified timepoints. Supine blood pressure was obtained after the participant had been supine for at least 5 minutes. When vital signs were scheduled at the same time as blood draws, the blood draws were obtained at the scheduled timepoint, and the vital signs were obtained as close to the scheduled blood draw as possible, but prior to the blood draw. The baseline value was defined as the last value recorded prior to the first dose in each treatment period. The normal reference range for supine systolic blood pressure was 90-140 millimetres of mercury (mmHg).
Time frame: Baseline and post-dose on Days 1 to 8 of Periods 1-3 (up to 27 days)
Population: Safety Population: all participants who received at least one dose of study drug, with participants grouped according to the treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Systolic Blood Pressure Over Time | Baseline (BL) - Value at Visit | 104.5 millimetres of mercury (mmHg) | Standard Deviation 12.03 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 8 | -3.4 millimetres of mercury (mmHg) | Standard Deviation 9.23 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 3 | -3.7 millimetres of mercury (mmHg) | Standard Deviation 7.46 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 7 | -5.2 millimetres of mercury (mmHg) | Standard Deviation 8.19 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 6 | -5.3 millimetres of mercury (mmHg) | Standard Deviation 8.94 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 4 | -2.8 millimetres of mercury (mmHg) | Standard Deviation 7.56 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 2 | -5.9 millimetres of mercury (mmHg) | Standard Deviation 6.93 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 1 | -1.7 millimetres of mercury (mmHg) | Standard Deviation 7.17 |
| GDC-9545 Tablet, Fasted: Treatment A | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 5 | -4.9 millimetres of mercury (mmHg) | Standard Deviation 7.03 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 2 | -4.0 millimetres of mercury (mmHg) | Standard Deviation 9.39 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 6 | -1.8 millimetres of mercury (mmHg) | Standard Deviation 6.39 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 1 | 0.7 millimetres of mercury (mmHg) | Standard Deviation 10.5 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 7 | -3.3 millimetres of mercury (mmHg) | Standard Deviation 7.31 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 8 | -0.4 millimetres of mercury (mmHg) | Standard Deviation 6.68 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 5 | -2.6 millimetres of mercury (mmHg) | Standard Deviation 6.46 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Systolic Blood Pressure Over Time | Baseline (BL) - Value at Visit | 103.1 millimetres of mercury (mmHg) | Standard Deviation 8.73 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 3 | -1.8 millimetres of mercury (mmHg) | Standard Deviation 8.71 |
| GDC-9545 Capsule, Fasted: Treatment B | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 4 | -3.2 millimetres of mercury (mmHg) | Standard Deviation 7.61 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 8 | -2.3 millimetres of mercury (mmHg) | Standard Deviation 6.28 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Systolic Blood Pressure Over Time | Baseline (BL) - Value at Visit | 102.6 millimetres of mercury (mmHg) | Standard Deviation 9.28 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 1 | -3.8 millimetres of mercury (mmHg) | Standard Deviation 7.33 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 2 | -1.2 millimetres of mercury (mmHg) | Standard Deviation 7.77 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 3 | -1.1 millimetres of mercury (mmHg) | Standard Deviation 8.39 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 4 | -2.6 millimetres of mercury (mmHg) | Standard Deviation 9.65 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 6 | -0.6 millimetres of mercury (mmHg) | Standard Deviation 8.95 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 7 | -2.9 millimetres of mercury (mmHg) | Standard Deviation 8.12 |
| GDC-9545 Capsule, Fed: Treatment C | Change From Baseline in Systolic Blood Pressure Over Time | Change from BL at Day 5 | -3.8 millimetres of mercury (mmHg) | Standard Deviation 6.71 |
Secondary
Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0)
The investigator sought information on adverse events (AEs) at each contact with a participant. All AEs, whether reported by the participant or noted by study personnel, were recorded. All AEs were assigned a severity grade (from 1 to 5) using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0). Severity refers to the intensity of an AE. The following is the severity grading scale used for AEs that are not specifically listed in the NCI-CTCAE: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening; and Grade 5 is death related to an AE.
Time frame: From first dose of study drug until 14 days after the last dose of study drug (up to 41 days)
Population: Safety Population: all participants who received at least one dose of study drug, with participants grouped according to the treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GDC-9545 Tablet, Fasted: Treatment A | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | Any Adverse Event (AE), Any Grade | 2 Participants |
| GDC-9545 Tablet, Fasted: Treatment A | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Initial Severity, Grade 3 | 0 Participants |
| GDC-9545 Tablet, Fasted: Treatment A | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Most Extreme Severity, Grade 2 | 0 Participants |
| GDC-9545 Tablet, Fasted: Treatment A | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Initial Severity, Grade 1 | 2 Participants |
| GDC-9545 Tablet, Fasted: Treatment A | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Most Extreme Severity, Grade 1 | 2 Participants |
| GDC-9545 Tablet, Fasted: Treatment A | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Initial Severity, Grade 4 | 0 Participants |
| GDC-9545 Tablet, Fasted: Treatment A | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Initial Severity, Grade 2 | 0 Participants |
| GDC-9545 Tablet, Fasted: Treatment A | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Most Extreme Severity, Grade 5 | 0 Participants |
| GDC-9545 Tablet, Fasted: Treatment A | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Most Extreme Severity, Grade 4 | 0 Participants |
| GDC-9545 Tablet, Fasted: Treatment A | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Initial Severity, Grade 5 | 0 Participants |
| GDC-9545 Tablet, Fasted: Treatment A | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Most Extreme Severity, Grade 3 | 0 Participants |
| GDC-9545 Capsule, Fasted: Treatment B | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Initial Severity, Grade 5 | 0 Participants |
| GDC-9545 Capsule, Fasted: Treatment B | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Most Extreme Severity, Grade 3 | 0 Participants |
| GDC-9545 Capsule, Fasted: Treatment B | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Most Extreme Severity, Grade 1 | 2 Participants |
| GDC-9545 Capsule, Fasted: Treatment B | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Most Extreme Severity, Grade 2 | 0 Participants |
| GDC-9545 Capsule, Fasted: Treatment B | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Initial Severity, Grade 2 | 0 Participants |
| GDC-9545 Capsule, Fasted: Treatment B | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Most Extreme Severity, Grade 5 | 0 Participants |
| GDC-9545 Capsule, Fasted: Treatment B | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Initial Severity, Grade 3 | 0 Participants |
| GDC-9545 Capsule, Fasted: Treatment B | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Most Extreme Severity, Grade 4 | 0 Participants |
| GDC-9545 Capsule, Fasted: Treatment B | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Initial Severity, Grade 4 | 0 Participants |
| GDC-9545 Capsule, Fasted: Treatment B | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Initial Severity, Grade 1 | 2 Participants |
| GDC-9545 Capsule, Fasted: Treatment B | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | Any Adverse Event (AE), Any Grade | 2 Participants |
| GDC-9545 Capsule, Fed: Treatment C | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Most Extreme Severity, Grade 4 | 0 Participants |
| GDC-9545 Capsule, Fed: Treatment C | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | Any Adverse Event (AE), Any Grade | 3 Participants |
| GDC-9545 Capsule, Fed: Treatment C | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Initial Severity, Grade 1 | 2 Participants |
| GDC-9545 Capsule, Fed: Treatment C | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Initial Severity, Grade 2 | 1 Participants |
| GDC-9545 Capsule, Fed: Treatment C | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Initial Severity, Grade 3 | 0 Participants |
| GDC-9545 Capsule, Fed: Treatment C | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Initial Severity, Grade 4 | 0 Participants |
| GDC-9545 Capsule, Fed: Treatment C | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Initial Severity, Grade 5 | 0 Participants |
| GDC-9545 Capsule, Fed: Treatment C | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Most Extreme Severity, Grade 1 | 2 Participants |
| GDC-9545 Capsule, Fed: Treatment C | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Most Extreme Severity, Grade 2 | 1 Participants |
| GDC-9545 Capsule, Fed: Treatment C | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Most Extreme Severity, Grade 3 | 0 Participants |
| GDC-9545 Capsule, Fed: Treatment C | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Most Extreme Severity, Grade 5 | 0 Participants |
| Overall: Any GDC-9545 Treatment (A, B, or C) | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Initial Severity, Grade 5 | 0 Participants |
| Overall: Any GDC-9545 Treatment (A, B, or C) | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Most Extreme Severity, Grade 5 | 0 Participants |
| Overall: Any GDC-9545 Treatment (A, B, or C) | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Most Extreme Severity, Grade 3 | 0 Participants |
| Overall: Any GDC-9545 Treatment (A, B, or C) | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Initial Severity, Grade 4 | 0 Participants |
| Overall: Any GDC-9545 Treatment (A, B, or C) | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Initial Severity, Grade 3 | 0 Participants |
| Overall: Any GDC-9545 Treatment (A, B, or C) | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Initial Severity, Grade 2 | 1 Participants |
| Overall: Any GDC-9545 Treatment (A, B, or C) | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Most Extreme Severity, Grade 4 | 0 Participants |
| Overall: Any GDC-9545 Treatment (A, B, or C) | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Initial Severity, Grade 1 | 4 Participants |
| Overall: Any GDC-9545 Treatment (A, B, or C) | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | Any Adverse Event (AE), Any Grade | 5 Participants |
| Overall: Any GDC-9545 Treatment (A, B, or C) | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Most Extreme Severity, Grade 2 | 1 Participants |
| Overall: Any GDC-9545 Treatment (A, B, or C) | Number of Participants Who Experienced at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) | AE by Most Extreme Severity, Grade 1 | 4 Participants |
Secondary
Number of Participants With Clinically Significant Abnormalities in Clinical Chemistry, Hematology, and Urinalysis Laboratory Tests
Participants provided blood and urine samples at the specified timepoints for laboratory analysis of clinical chemistry, hematology, and urinalysis parameters (please refer to Appendix A of the protocol for a complete list of parameters). Any of the laboratory test results that were outside of the reference range were considered abnormalities. Not every laboratory abnormality qualified as an adverse event (AE). A laboratory test result was reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. All AEs were assigned a severity grade (from 1 to 5) using the NCI-CTCAE v5.0; for AEs not specifically listed in the NCI-CTCAE: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening; and Grade 5 is death related to an AE.
Time frame: Baseline, Days 2 and 8 of Period 1-3, and 12-14 days after last dose (up to 34 days)
Population: Safety Population: all participants who received at least one dose of study drug, with participants grouped according to the treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GDC-9545 Tablet, Fasted: Treatment A | Number of Participants With Clinically Significant Abnormalities in Clinical Chemistry, Hematology, and Urinalysis Laboratory Tests | 0 Participants |
| GDC-9545 Capsule, Fasted: Treatment B | Number of Participants With Clinically Significant Abnormalities in Clinical Chemistry, Hematology, and Urinalysis Laboratory Tests | 0 Participants |
| GDC-9545 Capsule, Fed: Treatment C | Number of Participants With Clinically Significant Abnormalities in Clinical Chemistry, Hematology, and Urinalysis Laboratory Tests | 1 Participants |