Evaluation of the Relative Bioavailability and Food Effect of GDC-9545 in Healthy Females of Non-Childbearing Potential
Sponsor
Genentech, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT04274075
Collaborator
(none)
18
1
6
1.3
13.4
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
18 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
A Phase 1, Open-Label, Single-Dose, Randomized, Three-Period Crossover Study to Evaluate the Relative Bioavailability and Food Effect of GDC-9545 in Healthy Female Subjects of Non-Childbearing Potential
Actual Study Start Date
:
Mar 6, 2020
Actual Primary Completion Date
:
Apr 16, 2020
Actual Study Completion Date
:
Apr 16, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: GDC-9545 Treatment Sequence A, B, and C Participants randomized to this arm will receive one dose of GDC-9545 at the start of each of three periods according to the treatment sequence A, B, and C (refer to the intervention descriptions). The washout period between doses will be a minimum of 10 days. |
Drug: GDC-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.
Other Names:
Drug: GDC-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.
Other Names:
Drug: GDC-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.
Other Names:
|
| Experimental: GDC-9545 Treatment Sequence B, C, and A Participants randomized to this arm will receive one dose of GDC-9545 at the start of each of three periods according to the treatment sequence B, C, and A (refer to the intervention descriptions). The washout period between doses will be a minimum of 10 days. |
Drug: GDC-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.
Other Names:
Drug: GDC-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.
Other Names:
Drug: GDC-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.
Other Names:
|
| Experimental: GDC-9545 Treatment Sequence C, A, and B Participants randomized to this arm will receive one dose of GDC-9545 at the start of each of three periods according to the treatment sequence C, A, and B (refer to the intervention descriptions). The washout period between doses will be a minimum of 10 days. |
Drug: GDC-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.
Other Names:
Drug: GDC-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.
Other Names:
Drug: GDC-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.
Other Names:
|
| Experimental: GDC-9545 Treatment Sequence A, C, and B Participants randomized to this arm will receive one dose of GDC-9545 at the start of each of three periods according to the treatment sequence A, C, and B (refer to the intervention descriptions). The washout period between doses will be a minimum of 10 days. |
Drug: GDC-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.
Other Names:
Drug: GDC-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.
Other Names:
Drug: GDC-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.
Other Names:
|
| Experimental: GDC-9545 Treatment Sequence B, A, and C Participants randomized to this arm will receive one dose of GDC-9545 at the start of each of three periods according to the treatment sequence B, A, and C (refer to the intervention descriptions). The washout period between doses will be a minimum of 10 days. |
Drug: GDC-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.
Other Names:
Drug: GDC-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.
Other Names:
Drug: GDC-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.
Other Names:
|
| Experimental: GDC-9545 Treatment Sequence C, B, and A Participants randomized to this arm will receive one dose of GDC-9545 at the start of each of three periods according to the treatment sequence C, B, and A (refer to the intervention descriptions). The washout period between doses will be a minimum of 10 days. |
Drug: GDC-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.
Other Names:
Drug: GDC-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.
Other Names:
Drug: GDC-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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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.
- 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.
Secondary Outcome Measures
- 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.
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
Female
Accepts 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Covance Research Unit - Daytona | Daytona Beach | Florida | United States | 32117 |
Sponsors and Collaborators
- Genentech, Inc.
Investigators
- Study Director: Clinical Trials, Genentech, Inc.
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT04274075
Other Study ID Numbers:
- GP42006
First Posted:
Feb 18, 2020
Last Update Posted:
Apr 28, 2021
Last Verified:
Mar 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. |
| Period Title: Overall Study | ||||||
| STARTED | 3 | 3 | 3 | 3 | 3 | 3 |
| Completed Treatment Period 1 (9 Days) | 3 | 3 | 3 | 3 | 3 | 3 |
| Completed Treatment Period 2 (9 Days) | 3 | 3 | 3 | 3 | 3 | 3 |
| Completed Treatment Period 3 (9 Days) | 3 | 3 | 3 | 3 | 3 | 3 |
| Completed Follow-up Visit | 3 | 3 | 3 | 3 | 3 | 3 |
| COMPLETED | 3 | 3 | 3 | 3 | 3 | 3 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. | Total of all reporting groups |
| Overall Participants | 3 | 3 | 3 | 3 | 3 | 3 | 18 |
| Age (Years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [Years] |
51.0
(4.4)
|
55.0
(5.2)
|
48.3
(8.1)
|
54.0
(9.5)
|
56.3
(5.9)
|
53.7
(4.9)
|
53.1
(6.2)
|
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
3
100%
|
3
100%
|
3
100%
|
3
100%
|
3
100%
|
3
100%
|
18
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||
| Hispanic or Latino |
2
66.7%
|
1
33.3%
|
2
66.7%
|
1
33.3%
|
2
66.7%
|
3
100%
|
11
61.1%
|
| Not Hispanic or Latino |
1
33.3%
|
2
66.7%
|
1
33.3%
|
2
66.7%
|
1
33.3%
|
0
0%
|
7
38.9%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||||
| White |
3
100%
|
3
100%
|
3
100%
|
3
100%
|
3
100%
|
3
100%
|
18
100%
|
Outcome Measures
| Title | Maximum Observed Plasma Concentration (Cmax) of GDC-9545 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|---|
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. |
| Measure Participants | 18 | 18 | 18 |
| Geometric Mean (Geometric Coefficient of Variation) [nanograms per millilitre (ng/mL)] |
126
(29.6)
|
129
(27.7)
|
102
(27.3)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | GDC-9545 Tablet, Fasted: Treatment A, GDC-9545 Capsule, Fasted: Treatment B |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.03 | |
| Confidence Interval |
(2-Sided) 90% 0.945 to 1.12 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The geometric mean ratio was calculated as Treatment B versus Treatment A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | GDC-9545 Capsule, Fasted: Treatment B, GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.790 | |
| Confidence Interval |
(2-Sided) 90% 0.726 to 0.859 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The geometric mean ratio was calculated as Treatment C versus Treatment B. | |
| Title | Time to Maximum Observed Plasma Concentration (Tmax) of GDC-9545 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|---|
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. |
| Measure Participants | 18 | 18 | 18 |
| Median (Full Range) [Hours] |
2.25
|
2.28
|
5.00
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | GDC-9545 Tablet, Fasted: Treatment A, GDC-9545 Capsule, Fasted: Treatment B |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Median Difference (Net) |
| Estimated Value | 0.525 | |
| Confidence Interval |
(2-Sided) 90% -0.225 to 1.50 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The Hodges-Lehmann estimate of median difference was calculated as Treatment B versus Treatment A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | GDC-9545 Capsule, Fasted: Treatment B, GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Median Difference (Net) |
| Estimated Value | 1.98 | |
| Confidence Interval |
(2-Sided) 90% 1.26 to 2.45 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The Hodges-Lehmann estimate of median difference was calculated as Treatment C versus Treatment B. | |
| Title | Time of Last Quantifiable Plasma Concentration (Tlast) of GDC-9545 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|---|
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. |
| Measure Participants | 18 | 18 | 18 |
| Median (Full Range) [Hours] |
168
|
168
|
168
|
| Title | Time to First Quantifiable Plasma Concentration (Tlag) of GDC-9545 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|---|
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. |
| Measure Participants | 18 | 18 | 18 |
| Median (Full Range) [Hours] |
0
|
0
|
0
|
| Title | Area Under the Plasma Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of GDC-9545 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|---|
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. |
| Measure Participants | 18 | 18 | 18 |
| Geometric Mean (Geometric Coefficient of Variation) [Hours*ng/mL] |
3710
(31.8)
|
3600
(29.8)
|
3310
(27.6)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | GDC-9545 Tablet, Fasted: Treatment A, GDC-9545 Capsule, Fasted: Treatment B |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.971 | |
| Confidence Interval |
(2-Sided) 90% 0.903 to 1.04 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The geometric mean ratio was calculated as Treatment B versus Treatment A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | GDC-9545 Capsule, Fasted: Treatment B, GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.919 | |
| Confidence Interval |
(2-Sided) 90% 0.855 to 0.988 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The geometric mean ratio was calculated as Treatment C versus Treatment B. | |
| Title | Area Under the Plasma Concentration-Time Curve From Hour 0 Extrapolated to Infinity (AUC0-∞) of GDC-9545 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|---|
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. |
| Measure Participants | 18 | 18 | 18 |
| Geometric Mean (Geometric Coefficient of Variation) [Hours*ng/mL] |
3860
(32.6)
|
3770
(30.8)
|
3460
(28.1)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | GDC-9545 Tablet, Fasted: Treatment A, GDC-9545 Capsule, Fasted: Treatment B |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.975 | |
| Confidence Interval |
(2-Sided) 90% 0.908 to 1.05 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The geometric mean ratio was calculated as Treatment B versus Treatment A. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | GDC-9545 Capsule, Fasted: Treatment B, GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.918 | |
| Confidence Interval |
(2-Sided) 90% 0.856 to 0.985 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The geometric mean ratio was calculated as Treatment C versus Treatment B. | |
| Title | 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 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|---|
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. |
| Measure Participants | 18 | 18 | 18 |
| Geometric Mean (Geometric Coefficient of Variation) [Percentage of AUC] |
3.40
(58.5)
|
3.87
(49.8)
|
3.78
(48.9)
|
| Title | Apparent Terminal Elimination Rate Constant (λz) of GDC-9545 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|---|
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. |
| Measure Participants | 18 | 18 | 18 |
| Geometric Mean (Geometric Coefficient of Variation) [Elimination rate per hour (/h)] |
0.0196
(15.7)
|
0.0185
(15.5)
|
0.0188
(14.4)
|
| Title | Apparent Terminal Elimination Half-Life (t1/2) of GDC-9545 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|---|
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. |
| Measure Participants | 18 | 18 | 18 |
| Geometric Mean (Geometric Coefficient of Variation) [Hours] |
35.4
(15.7)
|
37.4
(15.5)
|
36.9
(14.4)
|
| Title | Apparent Total Clearance (CL/F) of GDC-9545 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|---|
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. |
| Measure Participants | 18 | 18 | 18 |
| Geometric Mean (Geometric Coefficient of Variation) [Litres per hour (L/h)] |
7.76
(32.6)
|
7.97
(30.8)
|
8.68
(28.1)
|
| Title | Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of GDC-9545 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|---|
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. |
| Measure Participants | 18 | 18 | 18 |
| Geometric Mean (Geometric Coefficient of Variation) [Litres (L)] |
397
(29.8)
|
430
(26.5)
|
462
(29.8)
|
| Title | 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) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study drug, with participants grouped according to the treatment received. |
| Arm/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C | Overall: Any GDC-9545 Treatment (A, B, or C) |
|---|---|---|---|---|
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received at least one dose of any study drug (GDC-9545 Treatments A, B, or C). |
| Measure Participants | 18 | 18 | 18 | 18 |
| Any Adverse Event (AE), Any Grade |
2
66.7%
|
2
66.7%
|
3
100%
|
5
166.7%
|
| AE by Initial Severity, Grade 1 |
2
66.7%
|
2
66.7%
|
2
66.7%
|
4
133.3%
|
| AE by Initial Severity, Grade 2 |
0
0%
|
0
0%
|
1
33.3%
|
1
33.3%
|
| AE by Initial Severity, Grade 3 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| AE by Initial Severity, Grade 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| AE by Initial Severity, Grade 5 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| AE by Most Extreme Severity, Grade 1 |
2
66.7%
|
2
66.7%
|
2
66.7%
|
4
133.3%
|
| AE by Most Extreme Severity, Grade 2 |
0
0%
|
0
0%
|
1
33.3%
|
1
33.3%
|
| AE by Most Extreme Severity, Grade 3 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| AE by Most Extreme Severity, Grade 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| AE by Most Extreme Severity, Grade 5 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Clinically Significant Abnormalities in Clinical Chemistry, Hematology, and Urinalysis Laboratory Tests |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study drug, with participants grouped according to the treatment received. |
| Arm/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|---|
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. |
| Measure Participants | 18 | 18 | 18 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
1
33.3%
|
| Title | Change From Baseline in Systolic Blood Pressure Over Time |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study drug, with participants grouped according to the treatment received. |
| Arm/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|---|
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. |
| Measure Participants | 18 | 18 | 18 |
| Baseline (BL) - Value at Visit |
104.5
(12.03)
|
103.1
(8.73)
|
102.6
(9.28)
|
| Change from BL at Day 1 |
-1.7
(7.17)
|
0.7
(10.50)
|
-3.8
(7.33)
|
| Change from BL at Day 2 |
-5.9
(6.93)
|
-4.0
(9.39)
|
-1.2
(7.77)
|
| Change from BL at Day 3 |
-3.7
(7.46)
|
-1.8
(8.71)
|
-1.1
(8.39)
|
| Change from BL at Day 4 |
-2.8
(7.56)
|
-3.2
(7.61)
|
-2.6
(9.65)
|
| Change from BL at Day 5 |
-4.9
(7.03)
|
-2.6
(6.46)
|
-3.8
(6.71)
|
| Change from BL at Day 6 |
-5.3
(8.94)
|
-1.8
(6.39)
|
-0.6
(8.95)
|
| Change from BL at Day 7 |
-5.2
(8.19)
|
-3.3
(7.31)
|
-2.9
(8.12)
|
| Change from BL at Day 8 |
-3.4
(9.23)
|
-0.4
(6.68)
|
-2.3
(6.28)
|
| Title | Change From Baseline in Diastolic Blood Pressure Over Time |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study drug, with participants grouped according to the treatment received. |
| Arm/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|---|
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. |
| Measure Participants | 18 | 18 | 18 |
| Baseline (BL) - Value at Visit |
64.2
(7.86)
|
62.5
(8.40)
|
62.8
(7.67)
|
| Change from BL at Day 1 |
-2.8
(5.31)
|
-3.1
(6.73)
|
-3.3
(6.23)
|
| Change from BL at Day 2 |
-3.2
(6.13)
|
-2.7
(8.73)
|
-1.6
(6.64)
|
| Change from BL at Day 3 |
-4.2
(6.96)
|
0.2
(7.52)
|
-1.0
(6.87)
|
| Change from BL at Day 4 |
-2.3
(4.67)
|
-2.3
(7.50)
|
-2.3
(6.44)
|
| Change from BL at Day 5 |
-2.8
(7.36)
|
-0.9
(5.31)
|
-2.3
(6.82)
|
| Change from BL at Day 6 |
-4.3
(6.13)
|
-1.8
(6.37)
|
-0.4
(7.22)
|
| Change from BL at Day 7 |
-3.1
(7.07)
|
-0.9
(6.10)
|
-1.8
(6.83)
|
| Change from BL at Day 8 |
-3.1
(6.66)
|
0.1
(7.45)
|
-3.3
(7.39)
|
| Title | Change From Baseline in Pulse Rate Over Time |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study drug, with participants grouped according to the treatment received. |
| Arm/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|---|
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. |
| Measure Participants | 18 | 18 | 18 |
| Baseline (BL) - Value at Visit |
62.2
(7.61)
|
62.4
(8.88)
|
65.3
(11.00)
|
| Change from BL at Day 1 |
-2.1
(6.27)
|
-4.1
(7.62)
|
-1.3
(9.39)
|
| Change from BL at Day 2 |
1.4
(10.34)
|
-3.2
(7.65)
|
-5.4
(7.01)
|
| Change from BL at Day 3 |
-0.6
(5.61)
|
-4.1
(6.29)
|
-4.8
(7.73)
|
| Change from BL at Day 4 |
-1.1
(8.08)
|
-2.2
(9.52)
|
-5.6
(7.85)
|
| Change from BL at Day 5 |
-1.1
(6.76)
|
-2.8
(6.67)
|
-4.7
(9.33)
|
| Change from BL at Day 6 |
-0.2
(7.58)
|
-0.4
(8.60)
|
-4.4
(8.56)
|
| Change from BL at Day 7 |
-0.7
(7.10)
|
-1.4
(5.99)
|
-5.4
(8.20)
|
| Change from BL at Day 8 |
1.1
(9.00)
|
-0.1
(7.19)
|
-2.6
(6.30)
|
| Title | Change From Baseline in Respiratory Rate Over Time |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study drug, with participants grouped according to the treatment received. |
| Arm/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|---|
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. |
| Measure Participants | 18 | 18 | 18 |
| Baseline (BL) - Value at Visit |
15.6
(1.76)
|
15.6
(1.89)
|
15.6
(2.01)
|
| Change from BL at Day 1 |
1.6
(2.53)
|
1.2
(1.96)
|
2.0
(3.14)
|
| Change from BL at Day 2 |
-0.6
(2.90)
|
-0.7
(3.07)
|
-0.8
(2.29)
|
| Change from BL at Day 3 |
-0.4
(2.71)
|
-0.6
(3.55)
|
-0.6
(3.35)
|
| Change from BL at Day 4 |
0.1
(2.00)
|
0.2
(2.54)
|
-0.3
(2.68)
|
| Change from BL at Day 5 |
0.8
(3.60)
|
0.1
(2.70)
|
1.0
(2.93)
|
| Change from BL at Day 6 |
0.0
(2.74)
|
0.2
(2.37)
|
-0.6
(3.20)
|
| Change from BL at Day 7 |
-0.4
(3.26)
|
-1.0
(3.31)
|
-0.8
(3.15)
|
| Change from BL at Day 8 |
-0.9
(1.97)
|
-1.1
(2.30)
|
-1.0
(2.40)
|
| Title | Change From Baseline in Oral Body Temperature Over Time |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study drug, with participants grouped according to the treatment received. |
| Arm/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|---|
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. |
| Measure Participants | 18 | 18 | 18 |
| Baseline (BL) - Value at Visit |
36.65
(0.142)
|
36.64
(0.115)
|
36.72
(0.129)
|
| Change from BL at Day 1 |
0.06
(0.129)
|
0.00
(0.124)
|
0.04
(0.195)
|
| Change from BL at Day 2 |
0.12
(0.183)
|
0.07
(0.149)
|
0.00
(0.150)
|
| Change from BL at Day 3 |
0.12
(0.140)
|
0.11
(0.229)
|
0.03
(0.119)
|
| Change from BL at Day 4 |
0.08
(0.182)
|
0.09
(0.189)
|
0.03
(0.146)
|
| Change from BL at Day 5 |
0.12
(0.163)
|
0.11
(0.184)
|
0.03
(0.161)
|
| Change from BL at Day 6 |
0.08
(0.150)
|
0.11
(0.195)
|
0.03
(0.137)
|
| Change from BL at Day 7 |
0.08
(0.158)
|
0.10
(0.128)
|
0.06
(0.138)
|
| Change from BL at Day 8 |
0.12
(0.202)
|
0.13
(0.124)
|
0.01
(0.135)
|
| Title | Change From Baseline in Duration of PR, RR, QRS, QT, QTcB, and QTcF Intervals Over Time, as Measured by Electrocardiogram |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study drug, with participants grouped according to the treatment received. |
| Arm/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|---|
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. |
| Measure Participants | 18 | 18 | 18 |
| PR: Baseline (BL) - Value at Visit |
170.2
(15.38)
|
171.5
(13.87)
|
165.8
(17.39)
|
| PR: Change from BL at Day 1 |
-3.6
(5.80)
|
-6.1
(7.37)
|
-2.7
(13.46)
|
| PR: Change from BL at Day 2 |
-3.9
(10.65)
|
-4.8
(11.93)
|
4.4
(8.32)
|
| PR: Change from BL at Day 8 |
-2.1
(9.32)
|
-4.4
(9.43)
|
-1.0
(10.58)
|
| RR: Baseline (BL) - Value at Visit |
966.7
(115.12)
|
986.8
(106.40)
|
971.6
(131.35)
|
| RR: Change from BL at Day 1 |
43.9
(64.10)
|
64.6
(113.36)
|
-6.0
(134.23)
|
| RR: Change from BL at Day 2 |
19.6
(88.42)
|
55.0
(97.58)
|
66.7
(89.61)
|
| RR: Change from BL at Day 8 |
-1.3
(74.84)
|
-12.6
(71.04)
|
9.9
(89.01)
|
| QRS: Baseline (BL) - Value at Visit |
87.4
(8.79)
|
88.9
(7.59)
|
89.4
(8.93)
|
| QRS: Change from BL at Day 1 |
-0.1
(5.01)
|
0.6
(3.66)
|
-4.4
(8.65)
|
| QRS: Change from BL at Day 2 |
0.7
(5.01)
|
-0.7
(5.28)
|
-2.1
(5.78)
|
| QRS: Change from BL at Day 8 |
-0.6
(5.18)
|
-1.5
(4.93)
|
-1.7
(4.36)
|
| QT: Baseline (BL) - Value at Visit |
414.7
(21.01)
|
416.5
(18.51)
|
411.9
(25.22)
|
| QT: Change from BL at Day 1 |
5.9
(11.93)
|
11.4
(15.44)
|
-9.7
(18.23)
|
| QT: Change from BL at Day 2 |
0.5
(16.45)
|
5.7
(16.12)
|
11.9
(13.27)
|
| QT: Change from BL at Day 8 |
-2.6
(11.78)
|
-2.8
(10.71)
|
1.6
(15.15)
|
| QTcB: Baseline (BL) - Value at Visit |
422.3
(12.45)
|
419.9
(15.40)
|
418.7
(12.68)
|
| QTcB: Change from BL at Day 1 |
-3.3
(12.28)
|
-1.7
(12.72)
|
-7.9
(17.39)
|
| QTcB: Change from BL at Day 2 |
-3.4
(11.72)
|
-5.4
(10.99)
|
-2.1
(12.89)
|
| QTcB: Change from BL at Day 8 |
-2.4
(12.46)
|
-0.2
(11.90)
|
-0.6
(10.54)
|
| QTcF: Baseline (BL) - Value at Visit |
419.5
(11.10)
|
418.3
(12.85)
|
415.9
(11.91)
|
| QTcF: Change from BL at Day 1 |
-0.2
(10.38)
|
2.8
(8.50)
|
-8.5
(12.22)
|
| QTcF: Change from BL at Day 2 |
-2.1
(10.40)
|
-1.6
(8.82)
|
2.8
(9.58)
|
| QTcF: Change from BL at Day 8 |
-2.7
(9.54)
|
-1.0
(9.11)
|
0.1
(8.51)
|
| Title | Change From Baseline in Heart Rate Over Time, as Measured by Electrocardiogram |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study drug, grouped according to the treatment received. |
| Arm/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C |
|---|---|---|---|
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. |
| Measure Participants | 18 | 18 | 18 |
| Baseline (BL) - Value at Visit |
62.3
(6.96)
|
61.2
(6.71)
|
62.4
(9.62)
|
| Change from BL at Day 1 |
-2.9
(3.89)
|
-4.1
(6.53)
|
0.5
(8.36)
|
| Change from BL at Day 2 |
-1.0
(5.92)
|
-3.4
(6.03)
|
-4.6
(6.48)
|
| Change from BL at Day 8 |
-0.2
(5.31)
|
0.8
(4.71)
|
-0.9
(6.35)
|
Adverse Events
| Time Frame | From first dose of study drug until 14 days after the last dose of study drug (up to 41 days) | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C | Overall: Any GDC-9545 Treatment (A, B, or C) | ||||
| Arm/Group Description | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment A. Treatment A consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment B. Treatment B consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received one dose of GDC-9545 Treatment C. Treatment C consisted of 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. | This analysis population consisted of all participants who were enrolled in the study, regardless of the treatment sequence arm to which they were randomized, and received at least one dose of any study drug (GDC-9545 Treatments A, B, or C). | ||||
All Cause Mortality |
||||||||
| GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C | Overall: Any GDC-9545 Treatment (A, B, or C) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/18 (0%) | 0/18 (0%) | 0/18 (0%) | 0/18 (0%) | ||||
Serious Adverse Events |
||||||||
| GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C | Overall: Any GDC-9545 Treatment (A, B, or C) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/18 (0%) | 0/18 (0%) | 0/18 (0%) | 0/18 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| GDC-9545 Tablet, Fasted: Treatment A | GDC-9545 Capsule, Fasted: Treatment B | GDC-9545 Capsule, Fed: Treatment C | Overall: Any GDC-9545 Treatment (A, B, or C) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/18 (11.1%) | 2/18 (11.1%) | 3/18 (16.7%) | 5/18 (27.8%) | ||||
| Eye disorders | ||||||||
| Dry eye | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 |
| Gastrointestinal disorders | ||||||||
| Constipation | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 |
| Injury, poisoning and procedural complications | ||||||||
| Skin abrasion | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/18 (5.6%) | 1 |
| Investigations | ||||||||
| Blood creatine phosphokinase increased | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/18 (5.6%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Costochondritis | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 |
| Nervous system disorders | ||||||||
| Headache | 0/18 (0%) | 0 | 2/18 (11.1%) | 2 | 0/18 (0%) | 0 | 2/18 (11.1%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Upper-airway cough syndrome | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/18 (5.6%) | 1 |
| Vascular disorders | ||||||||
| Flushing | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 |
Limitations/Caveats
Caution should be used when interpreting results from the statistical analyses conducted in this study because the sample size is not based on power calculations.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but only after the first publication or presentation that involves the overall study. The Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
| Name/Title | Medical Communications |
|---|---|
| Organization | Genentech, Inc. |
| Phone | 800-821-8590 |
| genentech@druginfo.com |
Responsible Party:
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT04274075
Other Study ID Numbers:
- GP42006
First Posted:
Feb 18, 2020
Last Update Posted:
Apr 28, 2021
Last Verified:
Mar 1, 2021