Healthy Volunteers
Conditions
Brief summary
This is an open-label, single-center, two part study in healthy female subjects of non-childbearing potential to investigate the absorption, metabolism, and excretion of \[14C\]-GDC-9545 (Part 1), the absolute bioavailability of formulations F12 and F18 (i.e., GDC-9545/F12 capsule, 30 mg and GDC-9545/F18 capsule, 30 mg) and relative bioavailability of GDC-9545 oral capsule F18 to the F12 formulation (Part 2). It is planned that Part 1 will begin prior to Part 2 of the study, and that the two parts of the study will partially overlap.
Interventions
DRUG[14C]-GDC-9545
Participants will receive a single oral dose of \[14C\]-GDC-9545 capsule, 30 milligrams (mg) (not more than \[NMT\] 4.6 megabecquerel \[MBq\]; 124 microcurie \[μCi\]) with approximately 240 millilitres (mL) water in the fasted state.
DRUGGDC-9545 Solution for Infusion
Treatment B: 30 mg GDC-9545 as a solution for infusion, 3 mg/mL administered intravenously (IV) in 10 mL as an infusion over 30 minutes.
DRUGGDC-9545/F12 Capsule
Treatment C: GDC-9545/F12 capsule, 30 mg, administered orally with approximately 240 mL water.
DRUGGDC-9545/F18 Capsule
Treatment D: GDC-9545/F18 capsule, 30 mg, administered orally with approximately 240 mL water.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
30 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy female subjects of non-childbearing potential that are non-pregnant, non-lactating females, who are either postmenopausal or surgically sterile, aged 30 to 65 years, inclusive, at time of signing the Informed Consent Form (ICF) * A body mass index (BMI) between 18.5 and 32.0 kg/m\^2, inclusive, at screening * Ability to comply with the study protocol * Must have regular bowel movements (i.e., average stool production of ≥1 and ≤3 stools per day) (Part 1 only)
Exclusion criteria
* Women of childbearing potential, women who are pregnant or breastfeeding * Subjects who have received any investigational medicinal product (IMP) in a clinical research study within the 90 days prior to Day 1 (Part 1) or Day 1 of Period 1 (Part 2) * History of serious adverse reaction or serious hypersensitivity to any drug or allergy to the study drug formulation excipients * Subjects who are, or are immediate family members of, a study site or Sponsor employee * Subjects who have previously been administered IMP in this study. Subjects who have taken part in Part 1 are not permitted to take part in Part 2. * Evidence of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; i.e., the virus that causes COVID-19) infection * Positive for hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), or human immunodeficiency virus (HIV) antibody at screening * History of any drug or alcohol abuse in the past 2 years * Regular alcohol consumption \>14 units per week * A confirmed positive alcohol breath test at screening or admission * Current smokers and those who have smoked within the last 12 months * Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months * Confirmed positive drugs of abuse test result at screening or admission * Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 2017, shall participate in the study (Part 1 only) * Subjects who do not have suitable veins for multiple venipunctures/cannulation as assessed by the Investigator or delegate at screening * Clinically significant abnormal clinical chemistry, hematology, coagulation or urinalysis as judged by the Investigator * Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of \<70 mL/min using the Cockcroft-Gault equation * History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal (GI) disease (especially peptic ulceration, GI bleeding, ulcerative colitis, Crohn's Disease or Irritable Bowel Syndrome), neurological or psychiatric disorder, as judged by the Investigator * Presence or history of clinically significant allergy requiring treatment, as judged by the Investigator * Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood * Subjects who are taking, or have taken, any medication (e.g., prescription drugs, over-the-counter drugs, hormone replacement therapy \[HRT\], vaccines, topical medications, herbal or homeopathic remedies, nutritional supplements), other than up to 4 g of paracetamol per day, in the 14 days before IMP administration. Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as determined by the Investigator. * Subjects who are taking, or have taken, oral antibiotics within 4 weeks or IV antibiotics within 8 weeks prior to admission * Subjects who are taking, or have taken, any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to admission * History of GI surgery (with the exception of appendectomy unless it was performed within the previous 12 months) (Part 1 only) * Acute diarrhea or constipation in the 7 days before the predicted Day 1. If screening occurs \>7 days before the Day 1, this criterion will be determined on Day 1. Diarrhea will be defined as the passage of liquid feces and/or a stool frequency of greater than 3 times per day. Constipation will be defined as a failure to open the bowels for 3 days (Part 1 only) * Malabsorption syndrome or other condition that would interfere with enteral absorption * History or presence of an abnormal ECG that is clinically significant in the Investigator's opinion, including complete left bundle branch block, second- or third-degree atrioventricular heart block, or evidence of prior myocardial infarction * QT interval corrected through use of Fridericia's formula (QTcF) \>440 msec demonstrated by at least two ECGs \>30 minutes apart * History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome * Confirmed (e.g., 2 consecutive measurements) baseline heart rate ≤50 bpm prior to enrollment * Current treatment with medications that are well known to prolong the QT interval * Absolute neutrophil count \<1.3 x 10\^9/L (1300/μL) * Failure to satisfy the Investigator of fitness to participate for any other reason
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Relative Bioavailability Based on the Adjusted AUC(0-t) [Frel AUC(0-t)] of GDC-9545/F18 Capsule Calculated Relative to GDC-9545/F12 Capsule, Estimated in Plasma Samples | For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8 | Relative bioavailability of the GDC-9545/F18 capsule was calculated relative to the GDC-9545/F12 capsule based on the adjusted geometric mean AUC(0-t) values. Log-transformed AUC(0-t) was analyzed using mixed effects modelling techniques. The model included terms for treatment, sequence, and period fitted as fixed effects and subject nested within sequence as a random effect. |
| Part 1: Maximum Observed Concentration (Cmax), Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | Pre-dose and 1, 1.5, 2, 2.5, 3, 5, 6, 8, and 12 hours post-dose on Day 1, daily from Day 2 to Day 21, and Days 28, 35, and 42 | Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. Total radioactivity concentrations in plasma and whole blood were determined using liquid scintillation counting. The unit of measure for the total radioactivity concentrations is nanogram equivalent of free drug per millilitre. |
| Part 1: Time to Maximum Observed Concentration (Tmax), Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | Pre-dose and 1, 1.5, 2, 2.5, 3, 5, 6, 8, and 12 hours post-dose on Day 1, daily from Day 2 to Day 21, and Days 28, 35, and 42 | Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. Total radioactivity concentrations in plasma and whole blood were determined using liquid scintillation counting. |
| Part 1: Area Under the Concentration-Time Curve From Time 0 to 72 Hours [AUC(0-72)], Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | Pre-dose and post-dose at 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, and 72 hours | Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. Total radioactivity concentrations in plasma and whole blood were determined using liquid scintillation counting. |
| Part 1: Area Under the Concentration-Time Curve From Time 0 to the Time of Last Measurable Concentration [AUC(0-t)], Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | Pre-dose and 1, 1.5, 2, 2.5, 3, 5, 6, 8, and 12 hours post-dose on Day 1, daily from Day 2 to Day 21, and Days 28, 35, and 42 | Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. Total radioactivity concentrations in plasma and whole blood were determined using liquid scintillation counting. |
| Part 1: Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)], Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma | Pre-dose and 1, 1.5, 2, 2.5, 3, 5, 6, 8, and 12 hours post-dose on Day 1, daily from Day 2 to Day 21, and Days 28, 35, and 42 | Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. Total radioactivity (TR) concentrations in plasma and whole blood were determined using liquid scintillation counting. |
| Part 1: Terminal Elimination Half-Life (t1/2), Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | Pre-dose and 1, 1.5, 2, 2.5, 3, 5, 6, 8, and 12 hours post-dose on Day 1, daily from Day 2 to Day 21, and Days 28, 35, and 42 | Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. Total radioactivity (TR) concentrations in plasma and whole blood were determined using liquid scintillation counting. |
| Part 1: First Order Rate Constant Associated With Terminal Portion of the Curve (λz), Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | Pre-dose and 1, 1.5, 2, 2.5, 3, 5, 6, 8, and 12 hours post-dose on Day 1, daily from Day 2 to Day 21, and Days 28, 35, and 42 | Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. Total radioactivity concentrations in plasma and whole blood were determined using liquid scintillation counting. |
| Part 1: Total Body Clearance Calculated After a Single Extravascular Administration Where Fraction of Dose Bioavailable is Unknown (CL/F), Estimated for GDC-9545 in Plasma | Pre-dose and 1, 1.5, 2, 2.5, 3, 5, 6, 8, and 12 hours post-dose on Day 1, daily from Day 2 to Day 21, and Days 28, 35, and 42 | Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. Total radioactivity concentrations in plasma and whole blood were determined using liquid scintillation counting. |
| Part 1: Apparent Volume of Distribution Where Fraction of Dose Bioavailable is Unknown (Vz/F), Estimated for GDC-9545 in Plasma | Pre-dose and 1, 1.5, 2, 2.5, 3, 5, 6, 8, and 12 hours post-dose on Day 1, daily from Day 2 to Day 21, and Days 28, 35, and 42 | Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. Total radioactivity concentrations in plasma and whole blood were determined using liquid scintillation counting. |
| Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | Postdose at 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours | Total radioactivity concentrations in plasma and whole blood were determined using liquid scintillation counting. For calculation of the geometric mean, values reported as not detectable have been set to 0.5× the limit of detection (LOD); the LOD was 11.0 nanogram equivalent of free drug per millilitre (mL). |
| Part 1: Whole Blood to Plasma Total Radioactivity Concentration Ratios of [14C]-GDC-9545 at Specified Timepoints | Postdose at 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours | Total radioactivity concentrations in plasma and whole blood were determined using liquid scintillation counting. The limit of detection was 11.0 nanogram equivalent of free drug per millilitre (mL). |
| Part 2: Absolute Bioavailability (F) of GDC-9545/F12 and /F18 Capsules Calculated Relative to GDC-9545 Solution for Infusion Based on the Adjusted AUC(0-∞), Estimated in Plasma Samples | For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8 | Absolute bioavailability of the GDC-9545/F12 and /F18 capsules were calculated relative to GDC-9545 solution for infusion based on the adjusted geometric mean AUC(0-∞) values obtained after oral and intravenous (IV) administration of GDC-9545. Log-transformed AUC(0-∞) was analyzed using mixed effects modelling techniques. The model included terms for treatment and sequence fitted as fixed effects and subject within sequence fitted as a random effect. |
| Part 2: Relative Bioavailability Based on the Adjusted Cmax (Frel Cmax) of the GDC-9545/F18 Capsule Calculated Relative to the GDC-9545/F12 Capsule, Estimated in Plasma Samples | For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8 | Relative bioavailability of the GDC-9545/F18 capsule was calculated relative to the GDC-9545/F12 capsule based on the adjusted geometric mean Cmax values. Log-transformed Cmax was analyzed using mixed effects modelling techniques. The model included terms for treatment, sequence, and period fitted as fixed effects and subject nested within sequence as a random effect. |
| Part 2: Relative Bioavailability Based on the Adjusted AUC(0-∞) [Frel AUC(0-∞)] of the GDC-9545/F18 Capsule Calculated Relative to the GDC-9545/F12 Capsule, Estimated in Plasma Samples | For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8 | Relative bioavailability of the GDC-9545/F18 capsule was calculated relative to the GDC-9545/F12 capsule based on the adjusted geometric mean AUC(0-∞) values. Log-transformed AUC(0-∞) was analyzed using mixed effects modelling techniques. The model included terms for treatment, sequence, and period fitted as fixed effects and subject nested within sequence as a random effect. |
| Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) Over the Entire Collection Period | From Day 1 to Day 42 (0-1008 hours) | Following a single oral dose of 30 milligrams of \[14C\]-GDC-9545, urine and fecal samples were collected over time from each participant. The amounts of total radioactivity excreted in the samples were determined using liquid scintillation counting. The lower limits of detection in urine and fecal samples were 0.423 and 8.36 nanogram equivalent of free drug per gram of sample, respectively. Following Day 21 (480 hours), where urine/fecal collections were no longer continuous and spot sampling days commenced, interpolation of Ae was calculated to estimate the amount excreted on non-collection days (collection intervals with interpolated values included 480-648 hours, 672-816 hours, and 840-984 hours). |
| Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) Over the Entire Collection Period | From Day 1 to Day 42 (0-1008 hours) | Following a single oral dose of 30 milligrams of \[14C\]-GDC-9545, urine and fecal samples were collected over time from each participant. The amounts of total radioactivity excreted in the samples were determined using liquid scintillation counting. The lower limits of detection in urine and fecal samples were 0.423 and 8.36 nanogram equivalent of free drug per gram of sample, respectively. Following Day 21 (480 hours), where urine/fecal collections were no longer continuous and spot sampling days commenced, interpolation of Ae was calculated to estimate the amount excreted on non-collection days (collection intervals with interpolated values included 480-648 hours, 672-816 hours, and 840-984 hours). |
| Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 0-12, 12-24, 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216, 216-240, 240-264, 264-288, 288-312, 312-336, 336-360, 360-384, 384-408, 408-432, 432-456, 456-480, 480-648, 648-672, 672-816, 816-840, 840-984, & 984-1008 hours | Following a single oral dose of 30 milligrams of \[14C\]-GDC-9545, urine and fecal samples were collected over time from each participant. The amounts of total radioactivity excreted in the samples were determined using liquid scintillation counting. The lower limits of detection in urine and fecal samples were 0.423 and 8.36 nanogram equivalent of free drug per gram of sample, respectively. Following Day 21 (480 hours), where urine/fecal collections were no longer continuous and spot sampling days commenced, interpolation of Ae was calculated to estimate the amount excreted on non-collection days (collection intervals with interpolated values included 480-648 hours, 672-816 hours, and 840-984 hours). |
| Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-24, 0-48, 0-72, 0-96, 0-120, 0-144, 0-168, 0-192, 0-216, 0-240, 0-264, 0-288, 0-312, 0-336, 0-360, 0-384, 0-408, 0-432, 0-456, 0-480, 0-648, 0-672, 0-816, 0-840, 0-984, and 0-1008 hours | Following a single oral dose of 30 milligrams of \[14C\]-GDC-9545, urine and fecal samples were collected over time from each participant. The amounts of total radioactivity excreted in the samples were determined using liquid scintillation counting. The lower limits of detection in urine and fecal samples were 0.423 and 8.36 nanogram equivalent of free drug per gram of sample, respectively. Following Day 21 (480 hours), where urine/fecal collections were no longer continuous and spot sampling days commenced, interpolation of Ae was calculated to estimate the amount excreted on non-collection days (collection intervals with interpolated values included 480-648 hours, 672-816 hours, and 840-984 hours). |
| Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 0-12, 12-24, 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216, 216-240, 240-264, 264-288, 288-312, 312-336, 336-360, 360-384, 384-408, 408-432, 432-456, 456-480, 480-648, 648-672, 672-816, 816-840, 840-984, & 984-1008 hours | Following a single oral dose of 30 milligrams of \[14C\]-GDC-9545, urine and fecal samples were collected over time from each participant. The amounts of total radioactivity excreted in the samples were determined using liquid scintillation counting. The lower limits of detection in urine and fecal samples were 0.423 and 8.36 nanogram equivalent of free drug per gram of sample, respectively. Following Day 21 (480 hours), where urine/fecal collections were no longer continuous and spot sampling days commenced, interpolation of Ae was calculated to estimate the amount excreted on non-collection days (collection intervals with interpolated values included 480-648 hours, 672-816 hours, and 840-984 hours). |
| Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-24, 0-48, 0-72, 0-96, 0-120, 0-144, 0-168, 0-192, 0-216, 0-240, 0-264, 0-288, 0-312, 0-336, 0-360, 0-384, 0-408, 0-432, 0-456, 0-480, 0-648, 0-672, 0-816, 0-840, 0-984, and 0-1008 hours | Following a single oral dose of 30 milligrams of \[14C\]-GDC-9545, urine and fecal samples were collected over time from each participant. The amounts of total radioactivity excreted in the samples were determined using liquid scintillation counting. The lower limits of detection in urine and fecal samples were 0.423 and 8.36 nanogram equivalent of free drug per gram of sample, respectively. Following Day 21 (480 hours), where urine/fecal collections were no longer continuous and spot sampling days commenced, interpolation of Ae was calculated to estimate the amount excreted on non-collection days (collection intervals with interpolated values included 480-648 hours, 672-816 hours, and 840-984 hours). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Tmax for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8 | Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. |
| Part 2: AUC(0-t) for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8 | Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. |
| Part 2: AUC(0-∞) for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8 | Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. |
| Part 2: t1/2 for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8 | Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. |
| Part 2: First Order Rate Constant Associated With Terminal Portion of the Curve (λz) for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8 | Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. |
| Part 2: Total Body Clearance (CL) After a Single IV Administration for GDC-9545 Solution for Infusion, Estimated in Plasma Samples | For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8 | Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. |
| Part 2: Total Body Clearance Calculated After a Single Extravascular Administration Where Fraction of Dose Bioavailable is Unknown (CL/F) for GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8 | Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. |
| Part 2: Volume of Distribution Based on the Terminal Phase Calculated Using AUC(0-∞) After a Single IV Administration (Vz) for GDC-9545 Solution for Infusion, Estimated in Plasma Samples | For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8 | Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. |
| Part 2: Apparent Volume of Distribution Based on the Terminal Phase Calculated With AUC(0-∞) After a Single Extravascular Administration Where Fraction of Dose Bioavailable is Unknown (Vz/F) for GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8 | Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. |
| Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | From Baseline until end of study (up to 42 days and 35 days for Parts 1 and 2, respectively) | All adverse events (AEs) were recorded and the investigator independently assessed the seriousness and severity of each AE. AE severity was graded on a scale from 1 to 5 using the NCI-CTCAE v5.0; any events not specifically listed in the scale were defined as: 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. AEs of special interest were: Cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law; Cases of potential drug-induced kidney injury; Grade ≥3 nausea/vomiting/diarrhea; Grade ≥2 thromboembolic events; Grade ≥3 renal failure; Grade ≥3 hepatitis or elevation in ALT or AST; Grade ≥2 vaginal or uterine hemorrhage; Grade ≥2 bradycardia; Any grade of endometrial cancer; and, Suspected transmission of an infectious agent by the study drug. |
| Parts 1 and 2: Number of Participants With at Least One Abnormality in Laboratory Safety Tests, Reported as Adverse Events | Part 1: Baseline and Discharge Day (up to 21 days); Part 2: Baseline, Day -1 of each of the 3 treatment periods, and Discharge Day (up to 29 days) | Participants provided blood samples at the specified timepoints for laboratory analysis of clinical chemistry, hematology, and coagulation panels (please refer to Appendices 1 and 2 of the protocol for a complete list). Any of the laboratory test results that were outside of a parameter's normal 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. |
| Parts 1 and 2: Number of Participants With at Least One Abnormality in Vital Sign Measurements, Reported as Adverse Events | Part 1: Baseline, predose and 1, 4, and 24 hours postdose, and Discharge Day (up to 21 days); Part 2: Baseline, predose and 0.5, 1, 4, and 24 hours postdose for each of the 3 treatment periods, and Discharge Day (up to 29 days) | Vital sign measurements included pulse rate, systolic and diastolic blood pressure while the participant was in a supine position for 5 minutes, and oral temperature. Any of the vital sign results that were outside of a parameter's normal range were considered abnormalities. Not every vital sign abnormality qualified as an adverse event (AE). A vital sign 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. |
| Parts 1 and 2: Number of Participants With at Least One Abnormality in 12-Lead Electrocardiogram Measurements, Reported as Adverse Events | Part 1: Baseline (Day 1, predose), 1, 4, and 24 hours postdose, and Discharge Day (up to 21 days); Part 2: Baseline (Day 1, predose), 0.5, 1, 4, and 24 hours postdose for each of the 3 treatment periods, and Discharge Day (up to 29 days) | The 12-lead electrocardiograms (ECG) recorded measurements of heart rate, and PR, RR, QRS, uncorrected QT, and QTcF intervals. Any of the ECG parameter results that were outside of the normal range were considered abnormalities. Not every ECG abnormality qualified as an adverse event (AE). An ECG 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. |
| Part 2: Cmax for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8 | Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1: [14C]-GDC-9545 In Part 1, each participant received a single oral dose of Carbon-14 labelled \[14C\]-GDC-9545 capsule, 30 mg (NMT 4.6 MBq \[124 μCi\]). The test formulation was swallowed whole with approximately 240 mL water following an overnight fast of a minimum of 10 hours. | 6 |
| Part 2: GDC-9545 Treatment Sequence BCD In Part 2, participants were randomly allocated to one of two treatment sequences; Treatments B, C, and then D for this arm. In each of the three treatment periods, participants in the fasted state received a single 30-milligram (mg) dose of GDC-9545, administered as one of three possible formulations: Treatment B was 30-mg GDC-9545 as a solution for infusion, 3 mg/mL administered intravenously (IV) in 10 milliliters (mL) as an infusion over 30 minutes; Treatment C was a GDC-9545/F12 capsule, 30 mg, taken orally with approximately 240 mL water; and Treatment D was a GDC-9545/F18 capsule, 30 mg, taken orally with approximately 240 mL water. There was a minimum treatment-free washout period of 10 days between each study drug administration. | 5 |
| Part 2: GDC-9545 Treatment Sequence BDC In Part 2, participants were randomly allocated to one of two treatment sequences; Treatments B, D, and then C for this arm. In each of the three treatment periods, participants in the fasted state received a single 30-milligram (mg) dose of GDC-9545, administered as one of three possible formulations: Treatment B was 30-mg GDC-9545 as a solution for infusion, 3 mg/mL administered intravenously (IV) in 10 milliliters (mL) as an infusion over 30 minutes; Treatment D was a GDC-9545/F18 capsule, 30 mg, taken orally with approximately 240 mL water; and Treatment C was a GDC-9545/F12 capsule, 30 mg, taken orally with approximately 240 mL water. There was a minimum treatment-free washout period of 10 days between each study drug administration. | 5 |
| Total | 16 |
Baseline characteristics
| Characteristic | Part 1: [14C]-GDC-9545 | Total | Part 2: GDC-9545 Treatment Sequence BCD | Part 2: GDC-9545 Treatment Sequence BDC |
|---|---|---|---|---|
| Age, Continuous Part 1 | 56.2 Years STANDARD_DEVIATION 3.5 | 56.2 Years STANDARD_DEVIATION 3.5 | — | — |
| Age, Continuous Part 2 | — | 58.2 Years STANDARD_DEVIATION 4.3 | 58.8 Years STANDARD_DEVIATION 5.6 | 57.6 Years STANDARD_DEVIATION 3 |
| Ethnicity (NIH/OMB) Part 1 Hispanic or Latino | 0 Participants | 0 Participants | — | — |
| Ethnicity (NIH/OMB) Part 1 Not Hispanic or Latino | 6 Participants | 6 Participants | — | — |
| Ethnicity (NIH/OMB) Part 1 Unknown or Not Reported | 0 Participants | 0 Participants | — | — |
| Ethnicity (NIH/OMB) Part 2 Hispanic or Latino | — | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Part 2 Not Hispanic or Latino | — | 10 Participants | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Part 2 Unknown or Not Reported | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part 1 American Indian or Alaska Native | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Part 1 Asian | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Part 1 Black or African American | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Part 1 More than one race | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Part 1 Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Part 1 Unknown or Not Reported | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Part 1 White | 6 Participants | 6 Participants | — | — |
| Race (NIH/OMB) Part 2 American Indian or Alaska Native | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part 2 Asian | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part 2 Black or African American | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part 2 More than one race | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part 2 Native Hawaiian or Other Pacific Islander | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part 2 Unknown or Not Reported | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part 2 White | — | 10 Participants | 5 Participants | 5 Participants |
| Sex: Female, Male Part 1 Female | 6 Participants | 6 Participants | — | — |
| Sex: Female, Male Part 1 Male | 0 Participants | 0 Participants | — | — |
| Sex: Female, Male Part 2 Female | — | 10 Participants | 5 Participants | 5 Participants |
| Sex: Female, Male Part 2 Male | — | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 3 / 6 | 5 / 10 | 3 / 10 | 4 / 10 | 9 / 10 |
| serious Total, serious adverse events | 0 / 6 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Part 1: Apparent Volume of Distribution Where Fraction of Dose Bioavailable is Unknown (Vz/F), Estimated for GDC-9545 in Plasma
Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. Total radioactivity concentrations in plasma and whole blood were determined using liquid scintillation counting.
Time frame: Pre-dose and 1, 1.5, 2, 2.5, 3, 5, 6, 8, and 12 hours post-dose on Day 1, daily from Day 2 to Day 21, and Days 28, 35, and 42
Population: Pharmacokinetics (PK) Population, Part 1: all participants who received at least one dose and who satisfied the following criteria for at least one PK profile: no missing samples or invalid results at critical timepoints; no relevant protocol deviations; and, no relevant adverse events (such as vomiting).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Apparent Volume of Distribution Where Fraction of Dose Bioavailable is Unknown (Vz/F), Estimated for GDC-9545 in Plasma | 705 Litres per hour (L/h) | Geometric Coefficient of Variation 20.6 |
Primary
Part 1: Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)], Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma
Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. Total radioactivity (TR) concentrations in plasma and whole blood were determined using liquid scintillation counting.
Time frame: Pre-dose and 1, 1.5, 2, 2.5, 3, 5, 6, 8, and 12 hours post-dose on Day 1, daily from Day 2 to Day 21, and Days 28, 35, and 42
Population: Pharmacokinetics (PK) Population, Part 1: all participants who received at least one dose and who satisfied the following criteria for at least one PK profile: no missing samples or invalid results at critical timepoints; no relevant protocol deviations; and, no relevant adverse events (such as vomiting). 3 participants in the TR in plasma group were excluded from analysis because their parameter estimates were considered unreliable (i.e., extrapolated portion was \>20% of total).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)], Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma | 2680 nanogram*hours per milliltre (ng*h/mL) | Geometric Coefficient of Variation 43.2 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)], Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma | 6480 nanogram*hours per milliltre (ng*h/mL) | Geometric Coefficient of Variation 39.2 |
Primary
Part 1: Area Under the Concentration-Time Curve From Time 0 to 72 Hours [AUC(0-72)], Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood
Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. Total radioactivity concentrations in plasma and whole blood were determined using liquid scintillation counting.
Time frame: Pre-dose and post-dose at 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, and 72 hours
Population: Pharmacokinetics (PK) Population, Part 1: all participants who received at least one dose and who satisfied the following criteria for at least one PK profile: no missing samples or invalid results at critical timepoints; no relevant protocol deviations; and, no relevant adverse events (such as vomiting).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Area Under the Concentration-Time Curve From Time 0 to 72 Hours [AUC(0-72)], Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | 1930 nanogram*hours per milliltre (ng*h/mL) | Geometric Coefficient of Variation 32.2 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Area Under the Concentration-Time Curve From Time 0 to 72 Hours [AUC(0-72)], Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | 3370 nanogram*hours per milliltre (ng*h/mL) | Geometric Coefficient of Variation 24.4 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Area Under the Concentration-Time Curve From Time 0 to 72 Hours [AUC(0-72)], Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | 2530 nanogram*hours per milliltre (ng*h/mL) | Geometric Coefficient of Variation 22.5 |
Comparison: The geometric mean ratio was calculated for the AUC(0-72) of GDC-9545 in plasma samples compared with the AUC(0-72) of total radioactivity in plasma samples.
Comparison: The geometric mean ratio was calculated for the AUC(0-72) of total radioactivity (TR) in whole blood samples compared with the AUC(0-72) of TR in plasma samples.
Primary
Part 1: Area Under the Concentration-Time Curve From Time 0 to the Time of Last Measurable Concentration [AUC(0-t)], Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood
Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. Total radioactivity concentrations in plasma and whole blood were determined using liquid scintillation counting.
Time frame: Pre-dose and 1, 1.5, 2, 2.5, 3, 5, 6, 8, and 12 hours post-dose on Day 1, daily from Day 2 to Day 21, and Days 28, 35, and 42
Population: Pharmacokinetics (PK) Population, Part 1: all participants who received at least one dose and who satisfied the following criteria for at least one PK profile: no missing samples or invalid results at critical timepoints; no relevant protocol deviations; and, no relevant adverse events (such as vomiting).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Area Under the Concentration-Time Curve From Time 0 to the Time of Last Measurable Concentration [AUC(0-t)], Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | 2600 nanogram*hours per milliltre (ng*h/mL) | Geometric Coefficient of Variation 43.8 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Area Under the Concentration-Time Curve From Time 0 to the Time of Last Measurable Concentration [AUC(0-t)], Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | 4160 nanogram*hours per milliltre (ng*h/mL) | Geometric Coefficient of Variation 40.3 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Area Under the Concentration-Time Curve From Time 0 to the Time of Last Measurable Concentration [AUC(0-t)], Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | 3280 nanogram*hours per milliltre (ng*h/mL) | Geometric Coefficient of Variation 40.9 |
Comparison: The geometric mean ratio was calculated for the AUC(0-t) of GDC-9545 in plasma samples compared with the AUC(0-t) of total radioactivity in plasma samples.
Comparison: The geometric mean ratio was calculated for the AUC(0-t) of total radioactivity (TR) in whole blood samples compared with the AUC(0-t) of TR in plasma samples.
Primary
Part 1: First Order Rate Constant Associated With Terminal Portion of the Curve (λz), Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood
Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. Total radioactivity concentrations in plasma and whole blood were determined using liquid scintillation counting.
Time frame: Pre-dose and 1, 1.5, 2, 2.5, 3, 5, 6, 8, and 12 hours post-dose on Day 1, daily from Day 2 to Day 21, and Days 28, 35, and 42
Population: Pharmacokinetics (PK) Population, Part 1: all participants who received at least one dose and who satisfied the following criteria for at least one PK profile: no missing samples or invalid results at critical timepoints; no relevant protocol deviations; and, no relevant adverse events (such as vomiting). 3 participants in the TR in whole blood group were excluded from analysis because their parameter estimates were considered unreliable (i.e., coefficient of regression for terminal slope \<0.9).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 1: First Order Rate Constant Associated With Terminal Portion of the Curve (λz), Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | 0.0163 1/Hours | Geometric Coefficient of Variation 24.9 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: First Order Rate Constant Associated With Terminal Portion of the Curve (λz), Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | 0.0143 1/Hours | Geometric Coefficient of Variation 29.4 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: First Order Rate Constant Associated With Terminal Portion of the Curve (λz), Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | 0.0136 1/Hours | Geometric Coefficient of Variation 46.4 |
Primary
Part 1: Maximum Observed Concentration (Cmax), Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood
Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. Total radioactivity concentrations in plasma and whole blood were determined using liquid scintillation counting. The unit of measure for the total radioactivity concentrations is nanogram equivalent of free drug per millilitre.
Time frame: Pre-dose and 1, 1.5, 2, 2.5, 3, 5, 6, 8, and 12 hours post-dose on Day 1, daily from Day 2 to Day 21, and Days 28, 35, and 42
Population: Pharmacokinetics (PK) Population, Part 1: all participants who received at least one dose and who satisfied the following criteria for at least one PK profile: no missing samples or invalid results at critical timepoints; no relevant protocol deviations; and, no relevant adverse events (such as vomiting).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Maximum Observed Concentration (Cmax), Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | 74.3 nanogram per millilitre (ng/mL) | Geometric Coefficient of Variation 31.2 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Maximum Observed Concentration (Cmax), Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | 124 nanogram per millilitre (ng/mL) | Geometric Coefficient of Variation 21.4 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Maximum Observed Concentration (Cmax), Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | 88.0 nanogram per millilitre (ng/mL) | Geometric Coefficient of Variation 25.8 |
Primary
Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval
Following a single oral dose of 30 milligrams of \[14C\]-GDC-9545, urine and fecal samples were collected over time from each participant. The amounts of total radioactivity excreted in the samples were determined using liquid scintillation counting. The lower limits of detection in urine and fecal samples were 0.423 and 8.36 nanogram equivalent of free drug per gram of sample, respectively. Following Day 21 (480 hours), where urine/fecal collections were no longer continuous and spot sampling days commenced, interpolation of Ae was calculated to estimate the amount excreted on non-collection days (collection intervals with interpolated values included 480-648 hours, 672-816 hours, and 840-984 hours).
Time frame: 0-12, 12-24, 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216, 216-240, 240-264, 264-288, 288-312, 312-336, 336-360, 360-384, 384-408, 408-432, 432-456, 456-480, 480-648, 648-672, 672-816, 816-840, 840-984, & 984-1008 hours
Population: Mass Balance Population, Part 1: all participants who received a dose of study drug, had evaluable total radioactivity concentration (urinary and fecal) data, and had no protocol deviations that affected the mass balance analysis (e.g., spillage or missing collections, or vomiting). Only urine samples were collected over 2 intervals in the first 24 hours postdose: 0-12 hours and 12-24 hours; fecal samples were collected over a single 0-24 hours interval.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 384-408 hours | 17600 nanogram equivalent of free drug | Standard Deviation 3550 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 264-288 hours | 30000 nanogram equivalent of free drug | Standard Deviation 9410 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 288-312 hours | 27800 nanogram equivalent of free drug | Standard Deviation 9520 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 312-336 hours | 23200 nanogram equivalent of free drug | Standard Deviation 5850 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 336-360 hours | 25200 nanogram equivalent of free drug | Standard Deviation 4160 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 360-384 hours | 20300 nanogram equivalent of free drug | Standard Deviation 5510 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 240-264 hours | 35300 nanogram equivalent of free drug | Standard Deviation 13300 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 408-432 hours | 20800 nanogram equivalent of free drug | Standard Deviation 4430 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 432-456 hours | 17300 nanogram equivalent of free drug | Standard Deviation 2920 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 456-480 hours | 16300 nanogram equivalent of free drug | Standard Deviation 2940 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 480-648 hours | 114000 nanogram equivalent of free drug | Standard Deviation 22100 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 648-672 hours | 16300 nanogram equivalent of free drug | Standard Deviation 3820 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 672-816 hours | 93100 nanogram equivalent of free drug | Standard Deviation 19200 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 816-840 hours | 14700 nanogram equivalent of free drug | Standard Deviation 2830 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 840-984 hours | 83900 nanogram equivalent of free drug | Standard Deviation 15500 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 984-1008 hours | 13300 nanogram equivalent of free drug | Standard Deviation 2430 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 0-12 hours | 668000 nanogram equivalent of free drug | Standard Deviation 78600 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 12-24 hours | 307000 nanogram equivalent of free drug | Standard Deviation 54300 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 24-48 hours | 410000 nanogram equivalent of free drug | Standard Deviation 56400 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 48-72 hours | 242000 nanogram equivalent of free drug | Standard Deviation 50600 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 72-96 hours | 174000 nanogram equivalent of free drug | Standard Deviation 54800 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 96-120 hours | 129000 nanogram equivalent of free drug | Standard Deviation 48000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 120-144 hours | 94100 nanogram equivalent of free drug | Standard Deviation 41100 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 144-168 hours | 56100 nanogram equivalent of free drug | Standard Deviation 22000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 168-192 hours | 54300 nanogram equivalent of free drug | Standard Deviation 20300 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 192-216 hours | 49900 nanogram equivalent of free drug | Standard Deviation 21900 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 216-240 hours | 27700 nanogram equivalent of free drug | Standard Deviation 13600 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 216-240 hours | 732000 nanogram equivalent of free drug | Standard Deviation 1010000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 456-480 hours | 82000 nanogram equivalent of free drug | Standard Deviation 45000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 96-120 hours | 902000 nanogram equivalent of free drug | Standard Deviation 746000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 480-648 hours | 305000 nanogram equivalent of free drug | Standard Deviation 273000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 648-672 hours | 44300 nanogram equivalent of free drug | Standard Deviation 48600 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 192-216 hours | 438000 nanogram equivalent of free drug | Standard Deviation 596000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 672-816 hours | 362000 nanogram equivalent of free drug | Standard Deviation 296000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 120-144 hours | 2330000 nanogram equivalent of free drug | Standard Deviation 2590000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 816-840 hours | 88800 nanogram equivalent of free drug | Standard Deviation 70800 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 840-984 hours | 412000 nanogram equivalent of free drug | Standard Deviation 291000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 984-1008 hours | 48500 nanogram equivalent of free drug | Standard Deviation 30200 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 144-168 hours | 1180000 nanogram equivalent of free drug | Standard Deviation 894000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 0-24 hours | 6980 nanogram equivalent of free drug | Standard Deviation 17100 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 240-264 hours | 424000 nanogram equivalent of free drug | Standard Deviation 349000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 24-48 hours | 1980000 nanogram equivalent of free drug | Standard Deviation 3240000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 264-288 hours | 470000 nanogram equivalent of free drug | Standard Deviation 633000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 288-312 hours | 198000 nanogram equivalent of free drug | Standard Deviation 178000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 168-192 hours | 453000 nanogram equivalent of free drug | Standard Deviation 357000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 312-336 hours | 188000 nanogram equivalent of free drug | Standard Deviation 159000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 48-72 hours | 3880000 nanogram equivalent of free drug | Standard Deviation 4230000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 336-360 hours | 63700 nanogram equivalent of free drug | Standard Deviation 66000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 360-384 hours | 159000 nanogram equivalent of free drug | Standard Deviation 68800 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 384-408 hours | 122000 nanogram equivalent of free drug | Standard Deviation 95300 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 72-96 hours | 5730000 nanogram equivalent of free drug | Standard Deviation 4420000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 408-432 hours | 69100 nanogram equivalent of free drug | Standard Deviation 50400 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 432-456 hours | 73500 nanogram equivalent of free drug | Standard Deviation 54000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 336-360 hours | 88800 nanogram equivalent of free drug | Standard Deviation 67100 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 240-264 hours | 459000 nanogram equivalent of free drug | Standard Deviation 358000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 456-480 hours | 98200 nanogram equivalent of free drug | Standard Deviation 46000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 48-72 hours | 4120000 nanogram equivalent of free drug | Standard Deviation 4200000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 432-456 hours | 90700 nanogram equivalent of free drug | Standard Deviation 55900 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 480-648 hours | 401000 nanogram equivalent of free drug | Standard Deviation 161000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 96-120 hours | 1030000 nanogram equivalent of free drug | Standard Deviation 761000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 264-288 hours | 500000 nanogram equivalent of free drug | Standard Deviation 639000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 648-672 hours | 60600 nanogram equivalent of free drug | Standard Deviation 51700 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 24-48 hours | 2390000 nanogram equivalent of free drug | Standard Deviation 3250000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 360-384 hours | 179000 nanogram equivalent of free drug | Standard Deviation 70700 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 672-816 hours | 493000 nanogram equivalent of free drug | Standard Deviation 267000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 288-312 hours | 226000 nanogram equivalent of free drug | Standard Deviation 187000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 168-192 hours | 507000 nanogram equivalent of free drug | Standard Deviation 352000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 816-840 hours | 104000 nanogram equivalent of free drug | Standard Deviation 72300 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 120-144 hours | 2420000 nanogram equivalent of free drug | Standard Deviation 2620000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 408-432 hours | 89900 nanogram equivalent of free drug | Standard Deviation 51200 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 840-984 hours | 496000 nanogram equivalent of free drug | Standard Deviation 300000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 192-216 hours | 488000 nanogram equivalent of free drug | Standard Deviation 603000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 312-336 hours | 211000 nanogram equivalent of free drug | Standard Deviation 162000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 984-1008 hours | 61800 nanogram equivalent of free drug | Standard Deviation 32000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 384-408 hours | 139000 nanogram equivalent of free drug | Standard Deviation 96700 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 144-168 hours | 1240000 nanogram equivalent of free drug | Standard Deviation 905000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 72-96 hours | 5900000 nanogram equivalent of free drug | Standard Deviation 4380000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 0-24 hours | 982000 nanogram equivalent of free drug | Standard Deviation 140000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity (Ae) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 216-240 hours | 760000 nanogram equivalent of free drug | Standard Deviation 1020000 |
Primary
Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval
Following a single oral dose of 30 milligrams of \[14C\]-GDC-9545, urine and fecal samples were collected over time from each participant. The amounts of total radioactivity excreted in the samples were determined using liquid scintillation counting. The lower limits of detection in urine and fecal samples were 0.423 and 8.36 nanogram equivalent of free drug per gram of sample, respectively. Following Day 21 (480 hours), where urine/fecal collections were no longer continuous and spot sampling days commenced, interpolation of Ae was calculated to estimate the amount excreted on non-collection days (collection intervals with interpolated values included 480-648 hours, 672-816 hours, and 840-984 hours).
Time frame: 0-12, 12-24, 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216, 216-240, 240-264, 264-288, 288-312, 312-336, 336-360, 360-384, 384-408, 408-432, 432-456, 456-480, 480-648, 648-672, 672-816, 816-840, 840-984, & 984-1008 hours
Population: Mass Balance Population, Part 1: all participants who received a dose of study drug, had evaluable total radioactivity concentration (urinary and fecal) data, and had no protocol deviations that affected the mass balance analysis (e.g., spillage or missing collections, or vomiting). Only urine samples were collected over 2 intervals in the first 24 hours postdose: 0-12 hours and 12-24 hours; fecal samples were collected over a single 0-24 hours interval.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 12-24 hours | 0.997 Percentage of radioactive dose | Standard Deviation 0.176 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 216-240 hours | 0.090 Percentage of radioactive dose | Standard Deviation 0.044 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 672-816 hours | 0.303 Percentage of radioactive dose | Standard Deviation 0.062 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 72-96 hours | 0.566 Percentage of radioactive dose | Standard Deviation 0.178 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 240-264 hours | 0.115 Percentage of radioactive dose | Standard Deviation 0.043 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 144-168 hours | 0.182 Percentage of radioactive dose | Standard Deviation 0.072 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 480-648 hours | 0.371 Percentage of radioactive dose | Standard Deviation 0.072 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 264-288 hours | 0.098 Percentage of radioactive dose | Standard Deviation 0.031 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 816-840 hours | 0.048 Percentage of radioactive dose | Standard Deviation 0.009 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 24-48 hours | 1.331 Percentage of radioactive dose | Standard Deviation 0.183 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 288-312 hours | 0.090 Percentage of radioactive dose | Standard Deviation 0.031 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 456-480 hours | 0.053 Percentage of radioactive dose | Standard Deviation 0.01 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 96-120 hours | 0.420 Percentage of radioactive dose | Standard Deviation 0.156 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 312-336 hours | 0.075 Percentage of radioactive dose | Standard Deviation 0.019 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 48-72 hours | 0.787 Percentage of radioactive dose | Standard Deviation 0.164 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 840-984 hours | 0.273 Percentage of radioactive dose | Standard Deviation 0.05 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 336-360 hours | 0.082 Percentage of radioactive dose | Standard Deviation 0.014 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 648-672 hours | 0.053 Percentage of radioactive dose | Standard Deviation 0.012 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 192-216 hours | 0.162 Percentage of radioactive dose | Standard Deviation 0.071 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 360-384 hours | 0.066 Percentage of radioactive dose | Standard Deviation 0.018 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 984-1008 hours | 0.043 Percentage of radioactive dose | Standard Deviation 0.008 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 120-144 hours | 0.306 Percentage of radioactive dose | Standard Deviation 0.134 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 384-408 hours | 0.057 Percentage of radioactive dose | Standard Deviation 0.012 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 432-456 hours | 0.056 Percentage of radioactive dose | Standard Deviation 0.009 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 0-12 hours | 2.172 Percentage of radioactive dose | Standard Deviation 0.255 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 408-432 hours | 0.068 Percentage of radioactive dose | Standard Deviation 0.014 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 168-192 hours | 0.176 Percentage of radioactive dose | Standard Deviation 0.066 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 240-264 hours | 1.377 Percentage of radioactive dose | Standard Deviation 1.134 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 0-24 hours | 0.023 Percentage of radioactive dose | Standard Deviation 0.056 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 432-456 hours | 0.239 Percentage of radioactive dose | Standard Deviation 0.175 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 456-480 hours | 0.266 Percentage of radioactive dose | Standard Deviation 0.146 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 144-168 hours | 3.848 Percentage of radioactive dose | Standard Deviation 2.905 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 480-648 hours | 0.993 Percentage of radioactive dose | Standard Deviation 0.889 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 648-672 hours | 0.144 Percentage of radioactive dose | Standard Deviation 0.158 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 672-816 hours | 1.178 Percentage of radioactive dose | Standard Deviation 0.963 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 168-192 hours | 1.471 Percentage of radioactive dose | Standard Deviation 1.159 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 816-840 hours | 0.289 Percentage of radioactive dose | Standard Deviation 0.23 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 48-72 hours | 12.603 Percentage of radioactive dose | Standard Deviation 13.735 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 840-984 hours | 1.339 Percentage of radioactive dose | Standard Deviation 0.945 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 984-1008 hours | 0.158 Percentage of radioactive dose | Standard Deviation 0.098 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 192-216 hours | 1.424 Percentage of radioactive dose | Standard Deviation 1.937 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 216-240 hours | 2.379 Percentage of radioactive dose | Standard Deviation 3.28 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 408-432 hours | 0.225 Percentage of radioactive dose | Standard Deviation 0.164 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 72-96 hours | 18.625 Percentage of radioactive dose | Standard Deviation 14.351 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 264-288 hours | 1.528 Percentage of radioactive dose | Standard Deviation 2.056 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 288-312 hours | 0.644 Percentage of radioactive dose | Standard Deviation 0.58 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 312-336 hours | 0.612 Percentage of radioactive dose | Standard Deviation 0.518 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 96-120 hours | 2.932 Percentage of radioactive dose | Standard Deviation 2.423 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 336-360 hours | 0.207 Percentage of radioactive dose | Standard Deviation 0.214 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 24-48 hours | 6.428 Percentage of radioactive dose | Standard Deviation 10.516 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 360-384 hours | 0.517 Percentage of radioactive dose | Standard Deviation 0.224 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 384-408 hours | 0.396 Percentage of radioactive dose | Standard Deviation 0.31 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 120-144 hours | 7.565 Percentage of radioactive dose | Standard Deviation 8.42 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 984-1008 hours | 0.201 Percentage of radioactive dose | Standard Deviation 0.104 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 0-24 hours | 3.191 Percentage of radioactive dose | Standard Deviation 0.454 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 24-48 hours | 7.759 Percentage of radioactive dose | Standard Deviation 10.575 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 48-72 hours | 13.390 Percentage of radioactive dose | Standard Deviation 13.639 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 72-96 hours | 19.191 Percentage of radioactive dose | Standard Deviation 14.234 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 96-120 hours | 3.352 Percentage of radioactive dose | Standard Deviation 2.472 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 120-144 hours | 7.871 Percentage of radioactive dose | Standard Deviation 8.51 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 144-168 hours | 4.030 Percentage of radioactive dose | Standard Deviation 2.941 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 168-192 hours | 1.647 Percentage of radioactive dose | Standard Deviation 1.145 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 192-216 hours | 1.586 Percentage of radioactive dose | Standard Deviation 1.961 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 216-240 hours | 2.469 Percentage of radioactive dose | Standard Deviation 3.319 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 240-264 hours | 1.492 Percentage of radioactive dose | Standard Deviation 1.164 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 264-288 hours | 1.626 Percentage of radioactive dose | Standard Deviation 2.077 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 288-312 hours | 0.734 Percentage of radioactive dose | Standard Deviation 0.608 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 312-336 hours | 0.687 Percentage of radioactive dose | Standard Deviation 0.527 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 336-360 hours | 0.289 Percentage of radioactive dose | Standard Deviation 0.218 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 360-384 hours | 0.583 Percentage of radioactive dose | Standard Deviation 0.23 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 384-408 hours | 0.453 Percentage of radioactive dose | Standard Deviation 0.314 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 408-432 hours | 0.292 Percentage of radioactive dose | Standard Deviation 0.166 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 432-456 hours | 0.295 Percentage of radioactive dose | Standard Deviation 0.182 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 456-480 hours | 0.319 Percentage of radioactive dose | Standard Deviation 0.15 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 480-648 hours | 1.808 Percentage of radioactive dose | Standard Deviation 0.518 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 648-672 hours | 0.197 Percentage of radioactive dose | Standard Deviation 0.168 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 672-816 hours | 1.601 Percentage of radioactive dose | Standard Deviation 0.868 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 816-840 hours | 0.337 Percentage of radioactive dose | Standard Deviation 0.235 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (Fe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Collection Interval | 840-984 hours | 1.612 Percentage of radioactive dose | Standard Deviation 0.974 |
Primary
Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval
Following a single oral dose of 30 milligrams of \[14C\]-GDC-9545, urine and fecal samples were collected over time from each participant. The amounts of total radioactivity excreted in the samples were determined using liquid scintillation counting. The lower limits of detection in urine and fecal samples were 0.423 and 8.36 nanogram equivalent of free drug per gram of sample, respectively. Following Day 21 (480 hours), where urine/fecal collections were no longer continuous and spot sampling days commenced, interpolation of Ae was calculated to estimate the amount excreted on non-collection days (collection intervals with interpolated values included 480-648 hours, 672-816 hours, and 840-984 hours).
Time frame: 0-24, 0-48, 0-72, 0-96, 0-120, 0-144, 0-168, 0-192, 0-216, 0-240, 0-264, 0-288, 0-312, 0-336, 0-360, 0-384, 0-408, 0-432, 0-456, 0-480, 0-648, 0-672, 0-816, 0-840, 0-984, and 0-1008 hours
Population: Mass Balance Population, Part 1: all participants who received a dose of study drug, had evaluable total radioactivity concentration (urinary and fecal) data, and had no protocol deviations that affected the mass balance analysis (e.g., spillage or missing collections, or vomiting).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-168 hours | 2080000 nanogram equivalent of free drug | Standard Deviation 352000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-48 hours | 1380000 nanogram equivalent of free drug | Standard Deviation 175000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-72 hours | 1630000 nanogram equivalent of free drug | Standard Deviation 215000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-96 hours | 1800000 nanogram equivalent of free drug | Standard Deviation 262000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-120 hours | 1930000 nanogram equivalent of free drug | Standard Deviation 299000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-144 hours | 2020000 nanogram equivalent of free drug | Standard Deviation 334000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-24 hours | 975000 nanogram equivalent of free drug | Standard Deviation 128000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-192 hours | 2130000 nanogram equivalent of free drug | Standard Deviation 370000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-216 hours | 2180000 nanogram equivalent of free drug | Standard Deviation 389000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-240 hours | 2210000 nanogram equivalent of free drug | Standard Deviation 401000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-264 hours | 2250000 nanogram equivalent of free drug | Standard Deviation 413000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-288 hours | 2280000 nanogram equivalent of free drug | Standard Deviation 421000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-312 hours | 2300000 nanogram equivalent of free drug | Standard Deviation 430000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-336 hours | 2330000 nanogram equivalent of free drug | Standard Deviation 436000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-360 hours | 2350000 nanogram equivalent of free drug | Standard Deviation 439000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-384 hours | 2370000 nanogram equivalent of free drug | Standard Deviation 445000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-408 hours | 2390000 nanogram equivalent of free drug | Standard Deviation 448000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-432 hours | 2410000 nanogram equivalent of free drug | Standard Deviation 451000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-456 hours | 2430000 nanogram equivalent of free drug | Standard Deviation 454000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-480 hours | 2450000 nanogram equivalent of free drug | Standard Deviation 456000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-648 hours | 2560000 nanogram equivalent of free drug | Standard Deviation 473000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-672 hours | 2580000 nanogram equivalent of free drug | Standard Deviation 475000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-816 hours | 2670000 nanogram equivalent of free drug | Standard Deviation 488000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-840 hours | 2680000 nanogram equivalent of free drug | Standard Deviation 490000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-984 hours | 2770000 nanogram equivalent of free drug | Standard Deviation 501000 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-1008 hours | 2780000 nanogram equivalent of free drug | Standard Deviation 503000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-120 hours | 12500000 nanogram equivalent of free drug | Standard Deviation 5520000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-648 hours | 19800000 nanogram equivalent of free drug | Standard Deviation 1010000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-240 hours | 17600000 nanogram equivalent of free drug | Standard Deviation 1820000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-264 hours | 18100000 nanogram equivalent of free drug | Standard Deviation 1620000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-984 hours | 20700000 nanogram equivalent of free drug | Standard Deviation 719000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-288 hours | 18500000 nanogram equivalent of free drug | Standard Deviation 1280000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-672 hours | 19800000 nanogram equivalent of free drug | Standard Deviation 969000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-312 hours | 18700000 nanogram equivalent of free drug | Standard Deviation 1160000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-336 hours | 18900000 nanogram equivalent of free drug | Standard Deviation 1110000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-360 hours | 19000000 nanogram equivalent of free drug | Standard Deviation 1120000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-816 hours | 20200000 nanogram equivalent of free drug | Standard Deviation 742000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-384 hours | 19100000 nanogram equivalent of free drug | Standard Deviation 1110000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-408 hours | 19300000 nanogram equivalent of free drug | Standard Deviation 1060000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-432 hours | 19300000 nanogram equivalent of free drug | Standard Deviation 1070000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-24 hours | 6980 nanogram equivalent of free drug | Standard Deviation 17100 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-48 hours | 1980000 nanogram equivalent of free drug | Standard Deviation 3230000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-840 hours | 20300000 nanogram equivalent of free drug | Standard Deviation 733000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-72 hours | 5860000 nanogram equivalent of free drug | Standard Deviation 4840000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-456 hours | 19400000 nanogram equivalent of free drug | Standard Deviation 1030000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-96 hours | 11600000 nanogram equivalent of free drug | Standard Deviation 5790000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-144 hours | 14800000 nanogram equivalent of free drug | Standard Deviation 3120000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-480 hours | 19500000 nanogram equivalent of free drug | Standard Deviation 1050000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-168 hours | 16000000 nanogram equivalent of free drug | Standard Deviation 2740000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-192 hours | 16500000 nanogram equivalent of free drug | Standard Deviation 2840000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-1008 hours | 20700000 nanogram equivalent of free drug | Standard Deviation 712000 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-216 hours | 16900000 nanogram equivalent of free drug | Standard Deviation 2650000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-216 hours | 19100000 nanogram equivalent of free drug | Standard Deviation 2380000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-120 hours | 14400000 nanogram equivalent of free drug | Standard Deviation 5330000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-24 hours | 982000 nanogram equivalent of free drug | Standard Deviation 140000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-240 hours | 19800000 nanogram equivalent of free drug | Standard Deviation 1540000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-648 hours | 22300000 nanogram equivalent of free drug | Standard Deviation 966000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-432 hours | 21700000 nanogram equivalent of free drug | Standard Deviation 893000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-264 hours | 20300000 nanogram equivalent of free drug | Standard Deviation 1340000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-840 hours | 23000000 nanogram equivalent of free drug | Standard Deviation 847000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-48 hours | 3370000 nanogram equivalent of free drug | Standard Deviation 3230000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-288 hours | 20800000 nanogram equivalent of free drug | Standard Deviation 1030000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-192 hours | 18600000 nanogram equivalent of free drug | Standard Deviation 2590000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-144 hours | 16800000 nanogram equivalent of free drug | Standard Deviation 2880000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-312 hours | 21000000 nanogram equivalent of free drug | Standard Deviation 940000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-672 hours | 22400000 nanogram equivalent of free drug | Standard Deviation 922000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-72 hours | 7490000 nanogram equivalent of free drug | Standard Deviation 4750000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-336 hours | 21200000 nanogram equivalent of free drug | Standard Deviation 920000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-984 hours | 23500000 nanogram equivalent of free drug | Standard Deviation 949000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-168 hours | 18100000 nanogram equivalent of free drug | Standard Deviation 2510000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-360 hours | 21300000 nanogram equivalent of free drug | Standard Deviation 932000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-480 hours | 21900000 nanogram equivalent of free drug | Standard Deviation 878000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-96 hours | 13400000 nanogram equivalent of free drug | Standard Deviation 5640000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-384 hours | 21500000 nanogram equivalent of free drug | Standard Deviation 934000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-816 hours | 22900000 nanogram equivalent of free drug | Standard Deviation 825000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-456 hours | 21800000 nanogram equivalent of free drug | Standard Deviation 854000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-408 hours | 21600000 nanogram equivalent of free drug | Standard Deviation 894000 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-1008 hours | 23500000 nanogram equivalent of free drug | Standard Deviation 952000 |
Primary
Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) Over the Entire Collection Period
Following a single oral dose of 30 milligrams of \[14C\]-GDC-9545, urine and fecal samples were collected over time from each participant. The amounts of total radioactivity excreted in the samples were determined using liquid scintillation counting. The lower limits of detection in urine and fecal samples were 0.423 and 8.36 nanogram equivalent of free drug per gram of sample, respectively. Following Day 21 (480 hours), where urine/fecal collections were no longer continuous and spot sampling days commenced, interpolation of Ae was calculated to estimate the amount excreted on non-collection days (collection intervals with interpolated values included 480-648 hours, 672-816 hours, and 840-984 hours).
Time frame: From Day 1 to Day 42 (0-1008 hours)
Population: Mass Balance Population, Part 1: all participants who received a dose of study drug, had evaluable total radioactivity concentration (urinary and fecal) data, and had no protocol deviations that affected the mass balance analysis (e.g., spillage or missing collections, or vomiting).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) Over the Entire Collection Period | 2.78 milligram equivalent of free drug | Standard Deviation 0.503 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) Over the Entire Collection Period | 20.70 milligram equivalent of free drug | Standard Deviation 0.712 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity (CumAe) of [14C]-GDC-9545 Excreted in Urine, Feces, and Total (Urine and Feces Combined) Over the Entire Collection Period | 23.50 milligram equivalent of free drug | Standard Deviation 0.952 |
Primary
Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval
Following a single oral dose of 30 milligrams of \[14C\]-GDC-9545, urine and fecal samples were collected over time from each participant. The amounts of total radioactivity excreted in the samples were determined using liquid scintillation counting. The lower limits of detection in urine and fecal samples were 0.423 and 8.36 nanogram equivalent of free drug per gram of sample, respectively. Following Day 21 (480 hours), where urine/fecal collections were no longer continuous and spot sampling days commenced, interpolation of Ae was calculated to estimate the amount excreted on non-collection days (collection intervals with interpolated values included 480-648 hours, 672-816 hours, and 840-984 hours).
Time frame: 0-24, 0-48, 0-72, 0-96, 0-120, 0-144, 0-168, 0-192, 0-216, 0-240, 0-264, 0-288, 0-312, 0-336, 0-360, 0-384, 0-408, 0-432, 0-456, 0-480, 0-648, 0-672, 0-816, 0-840, 0-984, and 0-1008 hours
Population: Mass Balance Population, Part 1: all participants who received a dose of study drug, had evaluable total radioactivity concentration (urinary and fecal) data, and had no protocol deviations that affected the mass balance analysis (e.g., spillage or missing collections, or vomiting).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-168 hours | 6.761 Percentage of radioactive dose | Standard Deviation 1.144 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-48 hours | 4.500 Percentage of radioactive dose | Standard Deviation 0.57 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-72 hours | 5.286 Percentage of radioactive dose | Standard Deviation 0.7 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-96 hours | 5.853 Percentage of radioactive dose | Standard Deviation 0.85 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-120 hours | 6.272 Percentage of radioactive dose | Standard Deviation 0.973 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-144 hours | 6.578 Percentage of radioactive dose | Standard Deviation 1.086 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-24 hours | 3.169 Percentage of radioactive dose | Standard Deviation 0.415 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-192 hours | 6.937 Percentage of radioactive dose | Standard Deviation 1.203 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-216 hours | 7.099 Percentage of radioactive dose | Standard Deviation 1.264 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-240 hours | 7.189 Percentage of radioactive dose | Standard Deviation 1.303 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-264 hours | 7.304 Percentage of radioactive dose | Standard Deviation 1.343 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-288 hours | 7.401 Percentage of radioactive dose | Standard Deviation 1.369 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-312 hours | 7.492 Percentage of radioactive dose | Standard Deviation 1.399 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-336 hours | 7.567 Percentage of radioactive dose | Standard Deviation 1.416 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-360 hours | 7.649 Percentage of radioactive dose | Standard Deviation 1.428 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-384 hours | 7.715 Percentage of radioactive dose | Standard Deviation 1.445 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-408 hours | 7.772 Percentage of radioactive dose | Standard Deviation 1.455 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-432 hours | 7.839 Percentage of radioactive dose | Standard Deviation 1.467 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-456 hours | 7.895 Percentage of radioactive dose | Standard Deviation 1.475 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-480 hours | 7.948 Percentage of radioactive dose | Standard Deviation 1.483 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-648 hours | 8.319 Percentage of radioactive dose | Standard Deviation 1.536 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-672 hours | 8.372 Percentage of radioactive dose | Standard Deviation 1.543 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-816 hours | 8.675 Percentage of radioactive dose | Standard Deviation 1.585 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-840 hours | 8.723 Percentage of radioactive dose | Standard Deviation 1.592 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-984 hours | 8.995 Percentage of radioactive dose | Standard Deviation 1.629 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-1008 hours | 9.039 Percentage of radioactive dose | Standard Deviation 1.634 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-216 hours | 54.919 Percentage of radioactive dose | Standard Deviation 8.629 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-648 hours | 64.302 Percentage of radioactive dose | Standard Deviation 3.285 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-240 hours | 57.298 Percentage of radioactive dose | Standard Deviation 5.922 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-264 hours | 58.676 Percentage of radioactive dose | Standard Deviation 5.269 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-984 hours | 67.252 Percentage of radioactive dose | Standard Deviation 2.336 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-288 hours | 60.204 Percentage of radioactive dose | Standard Deviation 4.176 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-672 hours | 64.446 Percentage of radioactive dose | Standard Deviation 3.15 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-312 hours | 60.848 Percentage of radioactive dose | Standard Deviation 3.784 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-336 hours | 61.459 Percentage of radioactive dose | Standard Deviation 3.615 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-360 hours | 61.666 Percentage of radioactive dose | Standard Deviation 3.645 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-816 hours | 65.624 Percentage of radioactive dose | Standard Deviation 2.412 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-384 hours | 62.183 Percentage of radioactive dose | Standard Deviation 3.623 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-408 hours | 62.579 Percentage of radioactive dose | Standard Deviation 3.453 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-432 hours | 62.804 Percentage of radioactive dose | Standard Deviation 3.463 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-24 hours | 0.023 Percentage of radioactive dose | Standard Deviation 0.056 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-48 hours | 6.451 Percentage of radioactive dose | Standard Deviation 10.5 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-840 hours | 65.913 Percentage of radioactive dose | Standard Deviation 2.383 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-72 hours | 19.054 Percentage of radioactive dose | Standard Deviation 15.718 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-456 hours | 63.043 Percentage of radioactive dose | Standard Deviation 3.346 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-96 hours | 37.679 Percentage of radioactive dose | Standard Deviation 18.821 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-120 hours | 40.611 Percentage of radioactive dose | Standard Deviation 17.941 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-144 hours | 48.176 Percentage of radioactive dose | Standard Deviation 10.145 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-480 hours | 63.309 Percentage of radioactive dose | Standard Deviation 3.408 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-168 hours | 52.024 Percentage of radioactive dose | Standard Deviation 8.919 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-192 hours | 53.495 Percentage of radioactive dose | Standard Deviation 9.231 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-1008 hours | 67.410 Percentage of radioactive dose | Standard Deviation 2.313 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-168 hours | 58.785 Percentage of radioactive dose | Standard Deviation 8.143 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-120 hours | 46.884 Percentage of radioactive dose | Standard Deviation 17.339 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-24 hours | 3.191 Percentage of radioactive dose | Standard Deviation 0.454 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-240 hours | 64.487 Percentage of radioactive dose | Standard Deviation 4.999 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-648 hours | 73.065 Percentage of radioactive dose | Standard Deviation 2.673 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-432 hours | 70.643 Percentage of radioactive dose | Standard Deviation 2.903 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-264 hours | 65.979 Percentage of radioactive dose | Standard Deviation 4.345 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-840 hours | 75.200 Percentage of radioactive dose | Standard Deviation 2.365 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-48 hours | 10.950 Percentage of radioactive dose | Standard Deviation 10.498 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-288 hours | 67.605 Percentage of radioactive dose | Standard Deviation 3.358 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-480 hours | 71.257 Percentage of radioactive dose | Standard Deviation 2.853 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-144 hours | 54.755 Percentage of radioactive dose | Standard Deviation 9.345 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-312 hours | 68.339 Percentage of radioactive dose | Standard Deviation 3.055 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-672 hours | 73.262 Percentage of radioactive dose | Standard Deviation 2.54 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-72 hours | 24.340 Percentage of radioactive dose | Standard Deviation 15.443 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-336 hours | 69.026 Percentage of radioactive dose | Standard Deviation 2.99 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-984 hours | 76.812 Percentage of radioactive dose | Standard Deviation 2.771 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-216 hours | 62.018 Percentage of radioactive dose | Standard Deviation 7.723 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-360 hours | 69.315 Percentage of radioactive dose | Standard Deviation 3.029 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-192 hours | 60.432 Percentage of radioactive dose | Standard Deviation 8.41 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-96 hours | 43.532 Percentage of radioactive dose | Standard Deviation 18.32 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-384 hours | 69.898 Percentage of radioactive dose | Standard Deviation 3.035 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-816 hours | 74.863 Percentage of radioactive dose | Standard Deviation 2.281 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-456 hours | 70.938 Percentage of radioactive dose | Standard Deviation 2.774 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-408 hours | 70.351 Percentage of radioactive dose | Standard Deviation 2.905 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) by Cumulative Collection Interval | 0-1008 hours | 77.012 Percentage of radioactive dose | Standard Deviation 2.794 |
Primary
Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) Over the Entire Collection Period
Following a single oral dose of 30 milligrams of \[14C\]-GDC-9545, urine and fecal samples were collected over time from each participant. The amounts of total radioactivity excreted in the samples were determined using liquid scintillation counting. The lower limits of detection in urine and fecal samples were 0.423 and 8.36 nanogram equivalent of free drug per gram of sample, respectively. Following Day 21 (480 hours), where urine/fecal collections were no longer continuous and spot sampling days commenced, interpolation of Ae was calculated to estimate the amount excreted on non-collection days (collection intervals with interpolated values included 480-648 hours, 672-816 hours, and 840-984 hours).
Time frame: From Day 1 to Day 42 (0-1008 hours)
Population: Mass Balance Population, Part 1: all participants who received a dose of study drug, had evaluable total radioactivity concentration (urinary and fecal) data, and had no protocol deviations that affected the mass balance analysis (e.g., spillage or missing collections, or vomiting).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) Over the Entire Collection Period | 9.039 Percentage of radioactive dose | Standard Deviation 1.634 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) Over the Entire Collection Period | 67.410 Percentage of radioactive dose | Standard Deviation 2.313 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Mean Cumulative Amount of Total Radioactivity Expressed as a Percentage of the Radioactive Dose Administered (CumFe) of [14C]-GDC-9545 Recovered in Urine, Feces, and Total (Urine and Feces Combined) Over the Entire Collection Period | 77.012 Percentage of radioactive dose | Standard Deviation 2.794 |
Primary
Part 1: Terminal Elimination Half-Life (t1/2), Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood
Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. Total radioactivity (TR) concentrations in plasma and whole blood were determined using liquid scintillation counting.
Time frame: Pre-dose and 1, 1.5, 2, 2.5, 3, 5, 6, 8, and 12 hours post-dose on Day 1, daily from Day 2 to Day 21, and Days 28, 35, and 42
Population: Pharmacokinetics (PK) Population, Part 1: all participants who received at least one dose and who satisfied the following criteria for at least one PK profile: no missing samples or invalid results at critical timepoints; no relevant protocol deviations; and, no relevant adverse events (such as vomiting). 3 participants in the TR in whole blood group were excluded from analysis because their parameter estimates were considered unreliable (i.e., coefficient of regression for terminal slope \<0.9).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Terminal Elimination Half-Life (t1/2), Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | 42.6 Hours | Geometric Coefficient of Variation 24.9 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Terminal Elimination Half-Life (t1/2), Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | 48.4 Hours | Geometric Coefficient of Variation 29.4 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Terminal Elimination Half-Life (t1/2), Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | 50.8 Hours | Geometric Coefficient of Variation 46.4 |
Primary
Part 1: Time to Maximum Observed Concentration (Tmax), Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood
Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. Total radioactivity concentrations in plasma and whole blood were determined using liquid scintillation counting.
Time frame: Pre-dose and 1, 1.5, 2, 2.5, 3, 5, 6, 8, and 12 hours post-dose on Day 1, daily from Day 2 to Day 21, and Days 28, 35, and 42
Population: Pharmacokinetics (PK) Population, Part 1: all participants who received at least one dose and who satisfied the following criteria for at least one PK profile: no missing samples or invalid results at critical timepoints; no relevant protocol deviations; and, no relevant adverse events (such as vomiting).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Time to Maximum Observed Concentration (Tmax), Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | 3.50 Hours |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Time to Maximum Observed Concentration (Tmax), Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | 5.00 Hours |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 1: Time to Maximum Observed Concentration (Tmax), Estimated for GDC-9545 in Plasma and for Total Radioactivity in Plasma and Whole Blood | 5.00 Hours |
Primary
Part 1: Total Body Clearance Calculated After a Single Extravascular Administration Where Fraction of Dose Bioavailable is Unknown (CL/F), Estimated for GDC-9545 in Plasma
Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry. Total radioactivity concentrations in plasma and whole blood were determined using liquid scintillation counting.
Time frame: Pre-dose and 1, 1.5, 2, 2.5, 3, 5, 6, 8, and 12 hours post-dose on Day 1, daily from Day 2 to Day 21, and Days 28, 35, and 42
Population: Pharmacokinetics (PK) Population, Part 1: all participants who received at least one dose and who satisfied the following criteria for at least one PK profile: no missing samples or invalid results at critical timepoints; no relevant protocol deviations; and, no relevant adverse events (such as vomiting).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Total Body Clearance Calculated After a Single Extravascular Administration Where Fraction of Dose Bioavailable is Unknown (CL/F), Estimated for GDC-9545 in Plasma | 11.5 Litres per hour (L/h) | Geometric Coefficient of Variation 43.2 |
Primary
Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints
Total radioactivity concentrations in plasma and whole blood were determined using liquid scintillation counting. For calculation of the geometric mean, values reported as not detectable have been set to 0.5× the limit of detection (LOD); the LOD was 11.0 nanogram equivalent of free drug per millilitre (mL).
Time frame: Postdose at 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours
Population: Pharmacokinetics (PK) Population, Part 1: all participants who received at least one dose and who satisfied the following criteria for at least one PK profile: no missing samples or invalid results at critical timepoints; no relevant protocol deviations; and, no relevant adverse events (such as vomiting).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 1.5 Hours | 88.1 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 29.2 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 12 Hours | 66.6 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 22.5 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 4 Hours | 101 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 22.3 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 24 Hours | 45.6 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 24.4 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 2.5 Hours | 105 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 25.1 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 48 Hours | 34.5 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 29.5 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 5 Hours | 123 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 21.3 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 72 Hours | 22.7 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 31 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 2 Hours | 111 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 25.3 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 96 Hours | 16.1 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 64.5 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 6 Hours | 105 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 18.9 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 120 Hours | 9.88 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 74.7 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 3 Hours | 108 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 25.5 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 144 Hours | 7.91 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 60.3 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 8 Hours | 89.1 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 23.6 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 168 Hours | 6.64 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 46 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 1 Hour | 64.7 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 42.1 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 168 Hours | 7.44 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 49.2 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 1 Hour | 48.4 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 32.9 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 1.5 Hours | 66.7 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 24.8 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 2 Hours | 74.3 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 26.3 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 2.5 Hours | 76.7 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 27.2 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 3 Hours | 76.3 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 24.9 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 4 Hours | 74.4 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 21.9 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 5 Hours | 85.9 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 22.3 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 6 Hours | 70.4 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 19.5 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 8 Hours | 64.8 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 22.2 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 12 Hours | 52.3 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 20.8 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 24 Hours | 36.0 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 26.2 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 48 Hours | 24.6 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 26.3 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 72 Hours | 18.7 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 25 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 96 Hours | 9.97 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 74.9 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 120 Hours | 11.5 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 64.4 |
| Part 1: [14C]-GDC-9545 - Feces | Part 1: Total Radioactivity Concentrations of [14C]-GDC-9545 in Plasma and Whole Blood at Specified Timepoints | 144 Hours | 7.92 nanogram equivalent of free drug/mL | Geometric Coefficient of Variation 61 |
Primary
Part 1: Whole Blood to Plasma Total Radioactivity Concentration Ratios of [14C]-GDC-9545 at Specified Timepoints
Total radioactivity concentrations in plasma and whole blood were determined using liquid scintillation counting. The limit of detection was 11.0 nanogram equivalent of free drug per millilitre (mL).
Time frame: Postdose at 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours
Population: Pharmacokinetics (PK) Population, Part 1: all participants who received at least one dose and who satisfied the following criteria for at least one PK profile: no missing samples or invalid results at critical timepoints; no relevant protocol deviations; and, no relevant adverse events (such as vomiting). Participants were excluded from analysis at a given timepoint if total radioactivity was not detected in either their plasma or whole blood samples at that timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Whole Blood to Plasma Total Radioactivity Concentration Ratios of [14C]-GDC-9545 at Specified Timepoints | 1 Hour | 0.747 Ratio of concentrations (unitless) | Geometric Coefficient of Variation 12.1 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Whole Blood to Plasma Total Radioactivity Concentration Ratios of [14C]-GDC-9545 at Specified Timepoints | 1.5 Hours | 0.758 Ratio of concentrations (unitless) | Geometric Coefficient of Variation 6.7 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Whole Blood to Plasma Total Radioactivity Concentration Ratios of [14C]-GDC-9545 at Specified Timepoints | 2 Hours | 0.673 Ratio of concentrations (unitless) | Geometric Coefficient of Variation 5.4 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Whole Blood to Plasma Total Radioactivity Concentration Ratios of [14C]-GDC-9545 at Specified Timepoints | 2.5 Hours | 0.732 Ratio of concentrations (unitless) | Geometric Coefficient of Variation 2.9 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Whole Blood to Plasma Total Radioactivity Concentration Ratios of [14C]-GDC-9545 at Specified Timepoints | 3 Hours | 0.704 Ratio of concentrations (unitless) | Geometric Coefficient of Variation 4.6 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Whole Blood to Plasma Total Radioactivity Concentration Ratios of [14C]-GDC-9545 at Specified Timepoints | 4 Hours | 0.738 Ratio of concentrations (unitless) | Geometric Coefficient of Variation 0.7 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Whole Blood to Plasma Total Radioactivity Concentration Ratios of [14C]-GDC-9545 at Specified Timepoints | 5 Hours | 0.700 Ratio of concentrations (unitless) | Geometric Coefficient of Variation 10.6 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Whole Blood to Plasma Total Radioactivity Concentration Ratios of [14C]-GDC-9545 at Specified Timepoints | 6 Hours | 0.672 Ratio of concentrations (unitless) | Geometric Coefficient of Variation 2.8 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Whole Blood to Plasma Total Radioactivity Concentration Ratios of [14C]-GDC-9545 at Specified Timepoints | 8 Hours | 0.728 Ratio of concentrations (unitless) | Geometric Coefficient of Variation 4.1 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Whole Blood to Plasma Total Radioactivity Concentration Ratios of [14C]-GDC-9545 at Specified Timepoints | 12 Hours | 0.786 Ratio of concentrations (unitless) | Geometric Coefficient of Variation 10 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Whole Blood to Plasma Total Radioactivity Concentration Ratios of [14C]-GDC-9545 at Specified Timepoints | 24 Hours | 0.789 Ratio of concentrations (unitless) | Geometric Coefficient of Variation 7.4 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Whole Blood to Plasma Total Radioactivity Concentration Ratios of [14C]-GDC-9545 at Specified Timepoints | 48 Hours | 0.713 Ratio of concentrations (unitless) | Geometric Coefficient of Variation 5.6 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Whole Blood to Plasma Total Radioactivity Concentration Ratios of [14C]-GDC-9545 at Specified Timepoints | 72 Hours | 0.825 Ratio of concentrations (unitless) | Geometric Coefficient of Variation 7.6 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Whole Blood to Plasma Total Radioactivity Concentration Ratios of [14C]-GDC-9545 at Specified Timepoints | 96 Hours | 0.757 Ratio of concentrations (unitless) | Geometric Coefficient of Variation 2 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Whole Blood to Plasma Total Radioactivity Concentration Ratios of [14C]-GDC-9545 at Specified Timepoints | 120 Hours | 1.00 Ratio of concentrations (unitless) | Geometric Coefficient of Variation 30.7 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Whole Blood to Plasma Total Radioactivity Concentration Ratios of [14C]-GDC-9545 at Specified Timepoints | 144 Hours | 1.02 Ratio of concentrations (unitless) | Geometric Coefficient of Variation 27.5 |
| Part 1: [14C]-GDC-9545 - Urine | Part 1: Whole Blood to Plasma Total Radioactivity Concentration Ratios of [14C]-GDC-9545 at Specified Timepoints | 168 Hours | 0.843 Ratio of concentrations (unitless) | — |
Primary
Part 2: Absolute Bioavailability (F) of GDC-9545/F12 and /F18 Capsules Calculated Relative to GDC-9545 Solution for Infusion Based on the Adjusted AUC(0-∞), Estimated in Plasma Samples
Absolute bioavailability of the GDC-9545/F12 and /F18 capsules were calculated relative to GDC-9545 solution for infusion based on the adjusted geometric mean AUC(0-∞) values obtained after oral and intravenous (IV) administration of GDC-9545. Log-transformed AUC(0-∞) was analyzed using mixed effects modelling techniques. The model included terms for treatment and sequence fitted as fixed effects and subject within sequence fitted as a random effect.
Time frame: For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8
Population: Part 2 Pharmacokinetics (PK) Population Subset: all participants who received Treatments B and C or B and D and had reliable estimates of PK parameters for the assessment of relative bioavailability. One participant was excluded from analysis for both Treatments C and D because they did not have reliable estimates (i.e., pre-dose concentrations of GDC-9545 that were \>5% of Cmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 2: Absolute Bioavailability (F) of GDC-9545/F12 and /F18 Capsules Calculated Relative to GDC-9545 Solution for Infusion Based on the Adjusted AUC(0-∞), Estimated in Plasma Samples | 58.06 Percentage |
| Part 1: [14C]-GDC-9545 - Feces | Part 2: Absolute Bioavailability (F) of GDC-9545/F12 and /F18 Capsules Calculated Relative to GDC-9545 Solution for Infusion Based on the Adjusted AUC(0-∞), Estimated in Plasma Samples | 58.70 Percentage |
Primary
Part 2: Relative Bioavailability Based on the Adjusted AUC(0-∞) [Frel AUC(0-∞)] of the GDC-9545/F18 Capsule Calculated Relative to the GDC-9545/F12 Capsule, Estimated in Plasma Samples
Relative bioavailability of the GDC-9545/F18 capsule was calculated relative to the GDC-9545/F12 capsule based on the adjusted geometric mean AUC(0-∞) values. Log-transformed AUC(0-∞) was analyzed using mixed effects modelling techniques. The model included terms for treatment, sequence, and period fitted as fixed effects and subject nested within sequence as a random effect.
Time frame: For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8
Population: Part 2 Pharmacokinetics (PK) Population Subset: all participants who received Treatments C and D and had reliable estimates of PK parameters for the assessment of relative bioavailability. One participant was excluded from analysis because they did not have a reliable estimate (i.e., pre-dose concentration of GDC-9545 that was \>5% of Cmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 2: Relative Bioavailability Based on the Adjusted AUC(0-∞) [Frel AUC(0-∞)] of the GDC-9545/F18 Capsule Calculated Relative to the GDC-9545/F12 Capsule, Estimated in Plasma Samples | 102.04 Percentage |
Primary
Part 2: Relative Bioavailability Based on the Adjusted AUC(0-t) [Frel AUC(0-t)] of GDC-9545/F18 Capsule Calculated Relative to GDC-9545/F12 Capsule, Estimated in Plasma Samples
Relative bioavailability of the GDC-9545/F18 capsule was calculated relative to the GDC-9545/F12 capsule based on the adjusted geometric mean AUC(0-t) values. Log-transformed AUC(0-t) was analyzed using mixed effects modelling techniques. The model included terms for treatment, sequence, and period fitted as fixed effects and subject nested within sequence as a random effect.
Time frame: For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8
Population: Part 2 Pharmacokinetics (PK) Population Subset: all participants who received Treatments C and D and had reliable estimates of PK parameters for the assessment of relative bioavailability. One participant was excluded from analysis because they did not have a reliable estimate (i.e., pre-dose concentration of GDC-9545 that was \>5% of Cmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 2: Relative Bioavailability Based on the Adjusted AUC(0-t) [Frel AUC(0-t)] of GDC-9545/F18 Capsule Calculated Relative to GDC-9545/F12 Capsule, Estimated in Plasma Samples | 101.97 Percentage |
Primary
Part 2: Relative Bioavailability Based on the Adjusted Cmax (Frel Cmax) of the GDC-9545/F18 Capsule Calculated Relative to the GDC-9545/F12 Capsule, Estimated in Plasma Samples
Relative bioavailability of the GDC-9545/F18 capsule was calculated relative to the GDC-9545/F12 capsule based on the adjusted geometric mean Cmax values. Log-transformed Cmax was analyzed using mixed effects modelling techniques. The model included terms for treatment, sequence, and period fitted as fixed effects and subject nested within sequence as a random effect.
Time frame: For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8
Population: Part 2 Pharmacokinetics (PK) Population Subset: all participants who received Treatments C and D and had reliable estimates of PK parameters for the assessment of relative bioavailability. One participant was excluded from analysis because they did not have a reliable estimate (i.e., pre-dose concentration of GDC-9545 that was \>5% of Cmax).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 2: Relative Bioavailability Based on the Adjusted Cmax (Frel Cmax) of the GDC-9545/F18 Capsule Calculated Relative to the GDC-9545/F12 Capsule, Estimated in Plasma Samples | 100.79 Percentage |
Secondary
Part 2: Apparent Volume of Distribution Based on the Terminal Phase Calculated With AUC(0-∞) After a Single Extravascular Administration Where Fraction of Dose Bioavailable is Unknown (Vz/F) for GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples
Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry.
Time frame: For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8
Population: Pharmacokinetics (PK) Population, Part 2: all participants who received at least one dose and who satisfied the criteria for at least one PK profile. One participant was excluded from the PK analysis set for both Treatments C and D, owing to their having quantifiable pre-dose concentrations of GDC-9545 that were \>5% of Cmax for both treatments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 2: Apparent Volume of Distribution Based on the Terminal Phase Calculated With AUC(0-∞) After a Single Extravascular Administration Where Fraction of Dose Bioavailable is Unknown (Vz/F) for GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 466 Litres (L) | Geometric Coefficient of Variation 20 |
| Part 1: [14C]-GDC-9545 - Feces | Part 2: Apparent Volume of Distribution Based on the Terminal Phase Calculated With AUC(0-∞) After a Single Extravascular Administration Where Fraction of Dose Bioavailable is Unknown (Vz/F) for GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 476 Litres (L) | Geometric Coefficient of Variation 24.5 |
Secondary
Part 2: AUC(0-∞) for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples
Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry.
Time frame: For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8
Population: Pharmacokinetics (PK) Population, Part 2: all participants who received at least one dose and who satisfied the criteria for at least one PK profile. One participant was excluded from the PK analysis set for both Treatments C and D, owing to their having quantifiable pre-dose concentrations of GDC-9545 that were \>5% of Cmax for both treatments, and 1 participant was excluded from Treatment B analysis for having an unreliable AUC(0-∞) estimate (i.e., extrapolated portion \>20% of total).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 2: AUC(0-∞) for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 5630 ng*h/mL | Geometric Coefficient of Variation 32.5 |
| Part 1: [14C]-GDC-9545 - Feces | Part 2: AUC(0-∞) for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 3270 ng*h/mL | Geometric Coefficient of Variation 38.3 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 2: AUC(0-∞) for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 3300 ng*h/mL | Geometric Coefficient of Variation 42.2 |
Secondary
Part 2: AUC(0-t) for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples
Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry.
Time frame: For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8
Population: Pharmacokinetics (PK) Population, Part 2: all participants who received at least one dose and who satisfied the criteria for at least one PK profile. One participant was excluded from the PK analysis set for both Treatments C and D, owing to their having quantifiable pre-dose concentrations of GDC-9545 that were \>5% of Cmax for both treatments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 2: AUC(0-t) for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 5700 ng*h/mL | Geometric Coefficient of Variation 33.3 |
| Part 1: [14C]-GDC-9545 - Feces | Part 2: AUC(0-t) for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 3120 ng*h/mL | Geometric Coefficient of Variation 35.3 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 2: AUC(0-t) for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 3150 ng*h/mL | Geometric Coefficient of Variation 39.2 |
Secondary
Part 2: Cmax for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples
Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry.
Time frame: For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8
Population: Pharmacokinetics (PK) Population, Part 2: all participants who received at least one dose and who satisfied the criteria for at least one PK profile. One participant was excluded from the PK analysis set for both Treatments C and D, owing to their having quantifiable pre-dose concentrations of GDC-9545 that were \>5% of Cmax for both treatments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 2: Cmax for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 804 ng/mL | Geometric Coefficient of Variation 32.3 |
| Part 1: [14C]-GDC-9545 - Feces | Part 2: Cmax for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 94.1 ng/mL | Geometric Coefficient of Variation 23.1 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 2: Cmax for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 93.8 ng/mL | Geometric Coefficient of Variation 31.1 |
Secondary
Part 2: First Order Rate Constant Associated With Terminal Portion of the Curve (λz) for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples
Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry.
Time frame: For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8
Population: Pharmacokinetics (PK) Population, Part 2: all participants who received at least one dose and who satisfied the criteria for at least one PK profile. One participant was excluded from the PK analysis set for both Treatments C and D, owing to their having quantifiable pre-dose concentrations of GDC-9545 that were \>5% of Cmax for both treatments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 2: First Order Rate Constant Associated With Terminal Portion of the Curve (λz) for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 0.0184 1/Hours | Geometric Coefficient of Variation 33.9 |
| Part 1: [14C]-GDC-9545 - Feces | Part 2: First Order Rate Constant Associated With Terminal Portion of the Curve (λz) for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 0.0197 1/Hours | Geometric Coefficient of Variation 23.9 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 2: First Order Rate Constant Associated With Terminal Portion of the Curve (λz) for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 0.0191 1/Hours | Geometric Coefficient of Variation 21.6 |
Secondary
Part 2: t1/2 for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples
Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry.
Time frame: For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8
Population: Pharmacokinetics (PK) Population, Part 2: all participants who received at least one dose and who satisfied the criteria for at least one PK profile. One participant was excluded from the PK analysis set for both Treatments C and D, owing to their having quantifiable pre-dose concentrations of GDC-9545 that were \>5% of Cmax for both treatments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 2: t1/2 for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 37.8 hours | Geometric Coefficient of Variation 33.9 |
| Part 1: [14C]-GDC-9545 - Feces | Part 2: t1/2 for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 35.2 hours | Geometric Coefficient of Variation 23.9 |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 2: t1/2 for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 36.4 hours | Geometric Coefficient of Variation 21.6 |
Secondary
Part 2: Tmax for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples
Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry.
Time frame: For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8
Population: Pharmacokinetics (PK) Population, Part 2: all participants who received at least one dose and who satisfied the criteria for at least one PK profile. One participant was excluded from the PK analysis set for both Treatments C and D, owing to their having quantifiable pre-dose concentrations of GDC-9545 that were \>5% of Cmax for both treatments.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 2: Tmax for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 0.50 hours |
| Part 1: [14C]-GDC-9545 - Feces | Part 2: Tmax for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 5.00 hours |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Part 2: Tmax for GDC-9545 Solution for Infusion and GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 4.00 hours |
Secondary
Part 2: Total Body Clearance Calculated After a Single Extravascular Administration Where Fraction of Dose Bioavailable is Unknown (CL/F) for GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples
Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry.
Time frame: For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8
Population: Pharmacokinetics (PK) Population, Part 2: all participants who received at least one dose and who satisfied the criteria for at least one PK profile. One participant was excluded from the PK analysis set for both Treatments C and D, owing to their having quantifiable pre-dose concentrations of GDC-9545 that were \>5% of Cmax for both treatments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 2: Total Body Clearance Calculated After a Single Extravascular Administration Where Fraction of Dose Bioavailable is Unknown (CL/F) for GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 9.18 Litres per hour (L/h) | Geometric Coefficient of Variation 38.3 |
| Part 1: [14C]-GDC-9545 - Feces | Part 2: Total Body Clearance Calculated After a Single Extravascular Administration Where Fraction of Dose Bioavailable is Unknown (CL/F) for GDC-9545/F12 and /F18 Capsules, Estimated in Plasma Samples | 9.08 Litres per hour (L/h) | Geometric Coefficient of Variation 42.2 |
Secondary
Part 2: Total Body Clearance (CL) After a Single IV Administration for GDC-9545 Solution for Infusion, Estimated in Plasma Samples
Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry.
Time frame: For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8
Population: Pharmacokinetics (PK) Population, Part 2: all participants who received at least one dose and who satisfied the criteria for at least one PK profile. One participant was excluded from the PK analysis set because the AUC(0-∞) estimate was considered unreliable (i.e., extrapolated portion was \>20% of total).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 2: Total Body Clearance (CL) After a Single IV Administration for GDC-9545 Solution for Infusion, Estimated in Plasma Samples | 5.31 Litres per hour (L/h) | Geometric Coefficient of Variation 32.6 |
Secondary
Part 2: Volume of Distribution Based on the Terminal Phase Calculated Using AUC(0-∞) After a Single IV Administration (Vz) for GDC-9545 Solution for Infusion, Estimated in Plasma Samples
Pharmacokinetic parameters were estimated where possible and appropriate for each participant profile by non-compartmental analysis methods using Phoenix WinNonlin software. Plasma concentrations of GDC-9545 were determined using liquid chromatography with tandem mass spectrometry.
Time frame: For each treatment period: Pre-dose and 0.25, 0.5, 0.58, 0.67, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 hours post-dose on Day 1, and daily from Day 2 to Day 8
Population: Pharmacokinetics (PK) Population, Part 2: all participants who received at least one dose and who satisfied the criteria for at least one PK profile. One participant was excluded from the PK analysis set because the AUC(0-∞) estimate was considered unreliable (i.e., extrapolated portion was \>20% of total).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Part 2: Volume of Distribution Based on the Terminal Phase Calculated Using AUC(0-∞) After a Single IV Administration (Vz) for GDC-9545 Solution for Infusion, Estimated in Plasma Samples | 266 Litres (L) | Geometric Coefficient of Variation 21.5 |
Secondary
Parts 1 and 2: Number of Participants With at Least One Abnormality in 12-Lead Electrocardiogram Measurements, Reported as Adverse Events
The 12-lead electrocardiograms (ECG) recorded measurements of heart rate, and PR, RR, QRS, uncorrected QT, and QTcF intervals. Any of the ECG parameter results that were outside of the normal range were considered abnormalities. Not every ECG abnormality qualified as an adverse event (AE). An ECG 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.
Time frame: Part 1: Baseline (Day 1, predose), 1, 4, and 24 hours postdose, and Discharge Day (up to 21 days); Part 2: Baseline (Day 1, predose), 0.5, 1, 4, and 24 hours postdose for each of the 3 treatment periods, and Discharge Day (up to 29 days)
Population: Safety Population: all participants who received at least one dose of study drug, grouped according to the treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Parts 1 and 2: Number of Participants With at Least One Abnormality in 12-Lead Electrocardiogram Measurements, Reported as Adverse Events | 0 Participants |
| Part 1: [14C]-GDC-9545 - Feces | Parts 1 and 2: Number of Participants With at Least One Abnormality in 12-Lead Electrocardiogram Measurements, Reported as Adverse Events | 0 Participants |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Parts 1 and 2: Number of Participants With at Least One Abnormality in 12-Lead Electrocardiogram Measurements, Reported as Adverse Events | 0 Participants |
| Part 2: GDC-9545/F18 Capsule (Treatment D) | Parts 1 and 2: Number of Participants With at Least One Abnormality in 12-Lead Electrocardiogram Measurements, Reported as Adverse Events | 0 Participants |
Secondary
Parts 1 and 2: Number of Participants With at Least One Abnormality in Laboratory Safety Tests, Reported as Adverse Events
Participants provided blood samples at the specified timepoints for laboratory analysis of clinical chemistry, hematology, and coagulation panels (please refer to Appendices 1 and 2 of the protocol for a complete list). Any of the laboratory test results that were outside of a parameter's normal 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.
Time frame: Part 1: Baseline and Discharge Day (up to 21 days); Part 2: Baseline, Day -1 of each of the 3 treatment periods, and Discharge Day (up to 29 days)
Population: Safety Population: all participants who received at least one dose of study drug, grouped according to the treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Parts 1 and 2: Number of Participants With at Least One Abnormality in Laboratory Safety Tests, Reported as Adverse Events | 0 Participants |
| Part 1: [14C]-GDC-9545 - Feces | Parts 1 and 2: Number of Participants With at Least One Abnormality in Laboratory Safety Tests, Reported as Adverse Events | 0 Participants |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Parts 1 and 2: Number of Participants With at Least One Abnormality in Laboratory Safety Tests, Reported as Adverse Events | 0 Participants |
| Part 2: GDC-9545/F18 Capsule (Treatment D) | Parts 1 and 2: Number of Participants With at Least One Abnormality in Laboratory Safety Tests, Reported as Adverse Events | 0 Participants |
Secondary
Parts 1 and 2: Number of Participants With at Least One Abnormality in Vital Sign Measurements, Reported as Adverse Events
Vital sign measurements included pulse rate, systolic and diastolic blood pressure while the participant was in a supine position for 5 minutes, and oral temperature. Any of the vital sign results that were outside of a parameter's normal range were considered abnormalities. Not every vital sign abnormality qualified as an adverse event (AE). A vital sign 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.
Time frame: Part 1: Baseline, predose and 1, 4, and 24 hours postdose, and Discharge Day (up to 21 days); Part 2: Baseline, predose and 0.5, 1, 4, and 24 hours postdose for each of the 3 treatment periods, and Discharge Day (up to 29 days)
Population: Safety Population: all participants who received at least one dose of study drug, grouped according to the treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Parts 1 and 2: Number of Participants With at Least One Abnormality in Vital Sign Measurements, Reported as Adverse Events | 0 Participants |
| Part 1: [14C]-GDC-9545 - Feces | Parts 1 and 2: Number of Participants With at Least One Abnormality in Vital Sign Measurements, Reported as Adverse Events | 0 Participants |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Parts 1 and 2: Number of Participants With at Least One Abnormality in Vital Sign Measurements, Reported as Adverse Events | 0 Participants |
| Part 2: GDC-9545/F18 Capsule (Treatment D) | Parts 1 and 2: Number of Participants With at Least One Abnormality in Vital Sign Measurements, Reported as Adverse Events | 0 Participants |
Secondary
Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
All adverse events (AEs) were recorded and the investigator independently assessed the seriousness and severity of each AE. AE severity was graded on a scale from 1 to 5 using the NCI-CTCAE v5.0; any events not specifically listed in the scale were defined as: 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. AEs of special interest were: Cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law; Cases of potential drug-induced kidney injury; Grade ≥3 nausea/vomiting/diarrhea; Grade ≥2 thromboembolic events; Grade ≥3 renal failure; Grade ≥3 hepatitis or elevation in ALT or AST; Grade ≥2 vaginal or uterine hemorrhage; Grade ≥2 bradycardia; Any grade of endometrial cancer; and, Suspected transmission of an infectious agent by the study drug.
Time frame: From Baseline until end of study (up to 42 days and 35 days for Parts 1 and 2, respectively)
Population: Safety Population: all participants who received at least one dose of study drug, grouped according to the treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: [14C]-GDC-9545 - Urine | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE) | 3 Participants |
| Part 1: [14C]-GDC-9545 - Urine | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Serious AE | 0 Participants |
| Part 1: [14C]-GDC-9545 - Urine | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 1 AE | 3 Participants |
| Part 1: [14C]-GDC-9545 - Urine | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 2 AE | 0 Participants |
| Part 1: [14C]-GDC-9545 - Urine | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade ≥3 AE | 0 Participants |
| Part 1: [14C]-GDC-9545 - Urine | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE Related to Study Drug | 0 Participants |
| Part 1: [14C]-GDC-9545 - Urine | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE Leading to Withdrawal of Study Drug | 0 Participants |
| Part 1: [14C]-GDC-9545 - Urine | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE of Special Interest | 0 Participants |
| Part 1: [14C]-GDC-9545 - Feces | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 1 AE | 4 Participants |
| Part 1: [14C]-GDC-9545 - Feces | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE Related to Study Drug | 1 Participants |
| Part 1: [14C]-GDC-9545 - Feces | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE) | 5 Participants |
| Part 1: [14C]-GDC-9545 - Feces | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 2 AE | 1 Participants |
| Part 1: [14C]-GDC-9545 - Feces | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Serious AE | 0 Participants |
| Part 1: [14C]-GDC-9545 - Feces | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE of Special Interest | 0 Participants |
| Part 1: [14C]-GDC-9545 - Feces | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade ≥3 AE | 0 Participants |
| Part 1: [14C]-GDC-9545 - Feces | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE Leading to Withdrawal of Study Drug | 0 Participants |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE Leading to Withdrawal of Study Drug | 0 Participants |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE of Special Interest | 0 Participants |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 2 AE | 0 Participants |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE Related to Study Drug | 1 Participants |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 1 AE | 3 Participants |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Serious AE | 0 Participants |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE) | 3 Participants |
| Part 1: [14C]-GDC-9545 - Total (Urine and Feces) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade ≥3 AE | 0 Participants |
| Part 2: GDC-9545/F18 Capsule (Treatment D) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Serious AE | 0 Participants |
| Part 2: GDC-9545/F18 Capsule (Treatment D) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 1 AE | 2 Participants |
| Part 2: GDC-9545/F18 Capsule (Treatment D) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 2 AE | 2 Participants |
| Part 2: GDC-9545/F18 Capsule (Treatment D) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade ≥3 AE | 0 Participants |
| Part 2: GDC-9545/F18 Capsule (Treatment D) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE Related to Study Drug | 1 Participants |
| Part 2: GDC-9545/F18 Capsule (Treatment D) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE of Special Interest | 0 Participants |
| Part 2: GDC-9545/F18 Capsule (Treatment D) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE) | 4 Participants |
| Part 2: GDC-9545/F18 Capsule (Treatment D) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE Leading to Withdrawal of Study Drug | 0 Participants |
| Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 2 AE | 3 Participants |
| Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE of Special Interest | 0 Participants |
| Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade 1 AE | 6 Participants |
| Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE Leading to Withdrawal of Study Drug | 0 Participants |
| Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Any Adverse Event (AE) | 9 Participants |
| Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | AE Related to Study Drug | 3 Participants |
| Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Serious AE | 0 Participants |
| Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) | Parts 1 and 2: Number of Participants With at Least One Adverse Event, With Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) | Grade ≥3 AE | 0 Participants |