Trial Outcomes & Findings for Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-GDC-9545 Following a Single Oral Dose (Part 1) and to Evaluate the Absolute and Relative Bioavailability of Oral Capsule Formulations of GDC-9545 (Part 2) in Healthy Female Subjects of Non-Childbearing Potential (NCT NCT04680273)

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

16 participants

Primary outcome timeframe

From Day 1 to Day 42 (0-1008 hours)

Results posted on

2023-02-02

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.	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.
Overall Study STARTED	6	5	5
Overall Study Part 1: Received the Planned Dose of Study Drug	6	0	0
Overall Study Part 2: Received All 3 Planned Doses of Study Drug	0	5	5
Overall Study COMPLETED	6	5	5
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Baseline characteristics and results were analyzed separately for participants who were enrolled in Part 1 (N = 6) or Part 2 (N = 10) of the study.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 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).

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).

Outcome measures

Outcome measures
Measure	Part 1: [14C]-GDC-9545 - Urine n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine samples. 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.	Part 1: [14C]-GDC-9545 - Feces n=6 Participants This analysis group represents the total radioactivity recovered from the participants' fecal samples. 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.	Part 1: [14C]-GDC-9545 - Total (Urine and Feces) n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine and feces samples combined. 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	Part 2: GDC-9545/F18 Capsule (Treatment D) This safety analysis set includes all participants in Part 2 of the study during the treatment period in which they received a single dose of Treatment D: GDC-9545/F18 capsule, 30 mg, administered orally with approximately 240 mL water following an overnight fast of a minimum of 10 hours.	Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) This safety analysis set includes all participants in Part 2 who received the three planned doses of GDC-9545 (Treatments B, C, and D) and spans all three treatment periods. In Part 2 of the study, participants were randomly allocated to one of two treatment sequences: Treatments BCD or BDC. In each of the three treatment periods, participants received a single 30 mg dose of GDC-9545 in the fasted state; GDC-9545 was administered as one of three possible formulations. There was a minimum treatment-free washout period of 10 days between each study drug administration.
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	20.70 milligram equivalent of free drug Standard Deviation 0.712	23.50 milligram equivalent of free drug Standard Deviation 0.952	—	—

PRIMARY outcome

Timeframe: 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).

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).

Outcome measures

Outcome measures
Measure	Part 1: [14C]-GDC-9545 - Urine n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine samples. 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.	Part 1: [14C]-GDC-9545 - Feces n=6 Participants This analysis group represents the total radioactivity recovered from the participants' fecal samples. 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.	Part 1: [14C]-GDC-9545 - Total (Urine and Feces) n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine and feces samples combined. 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	Part 2: GDC-9545/F18 Capsule (Treatment D) This safety analysis set includes all participants in Part 2 of the study during the treatment period in which they received a single dose of Treatment D: GDC-9545/F18 capsule, 30 mg, administered orally with approximately 240 mL water following an overnight fast of a minimum of 10 hours.	Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) This safety analysis set includes all participants in Part 2 who received the three planned doses of GDC-9545 (Treatments B, C, and D) and spans all three treatment periods. In Part 2 of the study, participants were randomly allocated to one of two treatment sequences: Treatments BCD or BDC. In each of the three treatment periods, participants received a single 30 mg dose of GDC-9545 in the fasted state; GDC-9545 was administered as one of three possible formulations. There was a minimum treatment-free washout period of 10 days between each study drug administration.
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	67.410 Percentage of radioactive dose Standard Deviation 2.313	77.012 Percentage of radioactive dose Standard Deviation 2.794	—	—

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Part 1: [14C]-GDC-9545 - Urine n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine samples. 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.	Part 1: [14C]-GDC-9545 - Feces n=6 Participants This analysis group represents the total radioactivity recovered from the participants' fecal samples. 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.	Part 1: [14C]-GDC-9545 - Total (Urine and Feces) n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine and feces samples combined. 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	Part 2: GDC-9545/F18 Capsule (Treatment D) This safety analysis set includes all participants in Part 2 of the study during the treatment period in which they received a single dose of Treatment D: GDC-9545/F18 capsule, 30 mg, administered orally with approximately 240 mL water following an overnight fast of a minimum of 10 hours.	Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) This safety analysis set includes all participants in Part 2 who received the three planned doses of GDC-9545 (Treatments B, C, and D) and spans all three treatment periods. In Part 2 of the study, participants were randomly allocated to one of two treatment sequences: Treatments BCD or BDC. In each of the three treatment periods, participants received a single 30 mg dose of GDC-9545 in the fasted state; GDC-9545 was administered as one of three possible formulations. There was a minimum treatment-free washout period of 10 days between each study drug administration.
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: 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	1980000 nanogram equivalent of free drug Standard Deviation 3240000	2390000 nanogram equivalent of free drug Standard Deviation 3250000	—	—
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	5730000 nanogram equivalent of free drug Standard Deviation 4420000	5900000 nanogram equivalent of free drug Standard Deviation 4380000	—	—
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	902000 nanogram equivalent of free drug Standard Deviation 746000	1030000 nanogram equivalent of free drug Standard Deviation 761000	—	—
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	2330000 nanogram equivalent of free drug Standard Deviation 2590000	2420000 nanogram equivalent of free drug Standard Deviation 2620000	—	—
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	1180000 nanogram equivalent of free drug Standard Deviation 894000	1240000 nanogram equivalent of free drug Standard Deviation 905000	—	—
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	438000 nanogram equivalent of free drug Standard Deviation 596000	488000 nanogram equivalent of free drug Standard Deviation 603000	—	—
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	732000 nanogram equivalent of free drug Standard Deviation 1010000	760000 nanogram equivalent of free drug Standard Deviation 1020000	—	—
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	198000 nanogram equivalent of free drug Standard Deviation 178000	226000 nanogram equivalent of free drug Standard Deviation 187000	—	—
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	63700 nanogram equivalent of free drug Standard Deviation 66000	88800 nanogram equivalent of free drug Standard Deviation 67100	—	—
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	159000 nanogram equivalent of free drug Standard Deviation 68800	179000 nanogram equivalent of free drug Standard Deviation 70700	—	—
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	122000 nanogram equivalent of free drug Standard Deviation 95300	139000 nanogram equivalent of free drug Standard Deviation 96700	—	—
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	73500 nanogram equivalent of free drug Standard Deviation 54000	90700 nanogram equivalent of free drug Standard Deviation 55900	—	—
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	82000 nanogram equivalent of free drug Standard Deviation 45000	98200 nanogram equivalent of free drug Standard Deviation 46000	—	—
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	305000 nanogram equivalent of free drug Standard Deviation 273000	401000 nanogram equivalent of free drug Standard Deviation 161000	—	—
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	44300 nanogram equivalent of free drug Standard Deviation 48600	60600 nanogram equivalent of free drug Standard Deviation 51700	—	—
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	362000 nanogram equivalent of free drug Standard Deviation 296000	493000 nanogram equivalent of free drug Standard Deviation 267000	—	—
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	88800 nanogram equivalent of free drug Standard Deviation 70800	104000 nanogram equivalent of free drug Standard Deviation 72300	—	—
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	69100 nanogram equivalent of free drug Standard Deviation 50400	89900 nanogram equivalent of free drug Standard Deviation 51200	—	—
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: 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	982000 nanogram equivalent of free drug Standard Deviation 140000	—	—
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	3880000 nanogram equivalent of free drug Standard Deviation 4230000	4120000 nanogram equivalent of free drug Standard Deviation 4200000	—	—
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	453000 nanogram equivalent of free drug Standard Deviation 357000	507000 nanogram equivalent of free drug Standard Deviation 352000	—	—
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	424000 nanogram equivalent of free drug Standard Deviation 349000	459000 nanogram equivalent of free drug Standard Deviation 358000	—	—
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	470000 nanogram equivalent of free drug Standard Deviation 633000	500000 nanogram equivalent of free drug Standard Deviation 639000	—	—
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	188000 nanogram equivalent of free drug Standard Deviation 159000	211000 nanogram equivalent of free drug Standard Deviation 162000	—	—
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	412000 nanogram equivalent of free drug Standard Deviation 291000	496000 nanogram equivalent of free drug Standard Deviation 300000	—	—
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	48500 nanogram equivalent of free drug Standard Deviation 30200	61800 nanogram equivalent of free drug Standard Deviation 32000	—	—

PRIMARY outcome

Timeframe: 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).

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).

Outcome measures

Outcome measures
Measure	Part 1: [14C]-GDC-9545 - Urine n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine samples. 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.	Part 1: [14C]-GDC-9545 - Feces n=6 Participants This analysis group represents the total radioactivity recovered from the participants' fecal samples. 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.	Part 1: [14C]-GDC-9545 - Total (Urine and Feces) n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine and feces samples combined. 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	Part 2: GDC-9545/F18 Capsule (Treatment D) This safety analysis set includes all participants in Part 2 of the study during the treatment period in which they received a single dose of Treatment D: GDC-9545/F18 capsule, 30 mg, administered orally with approximately 240 mL water following an overnight fast of a minimum of 10 hours.	Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) This safety analysis set includes all participants in Part 2 who received the three planned doses of GDC-9545 (Treatments B, C, and D) and spans all three treatment periods. In Part 2 of the study, participants were randomly allocated to one of two treatment sequences: Treatments BCD or BDC. In each of the three treatment periods, participants received a single 30 mg dose of GDC-9545 in the fasted state; GDC-9545 was administered as one of three possible formulations. There was a minimum treatment-free washout period of 10 days between each study drug administration.
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	1980000 nanogram equivalent of free drug Standard Deviation 3230000	3370000 nanogram equivalent of free drug Standard Deviation 3230000	—	—
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	5860000 nanogram equivalent of free drug Standard Deviation 4840000	7490000 nanogram equivalent of free drug Standard Deviation 4750000	—	—
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	12500000 nanogram equivalent of free drug Standard Deviation 5520000	14400000 nanogram equivalent of free drug Standard Deviation 5330000	—	—
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	14800000 nanogram equivalent of free drug Standard Deviation 3120000	16800000 nanogram equivalent of free drug Standard Deviation 2880000	—	—
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	16000000 nanogram equivalent of free drug Standard Deviation 2740000	18100000 nanogram equivalent of free drug Standard Deviation 2510000	—	—
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	16500000 nanogram equivalent of free drug Standard Deviation 2840000	18600000 nanogram equivalent of free drug Standard Deviation 2590000	—	—
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	16900000 nanogram equivalent of free drug Standard Deviation 2650000	19100000 nanogram equivalent of free drug Standard Deviation 2380000	—	—
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	17600000 nanogram equivalent of free drug Standard Deviation 1820000	19800000 nanogram equivalent of free drug Standard Deviation 1540000	—	—
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	18500000 nanogram equivalent of free drug Standard Deviation 1280000	20800000 nanogram equivalent of free drug Standard Deviation 1030000	—	—
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	18700000 nanogram equivalent of free drug Standard Deviation 1160000	21000000 nanogram equivalent of free drug Standard Deviation 940000	—	—
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	19400000 nanogram equivalent of free drug Standard Deviation 1030000	21800000 nanogram equivalent of free drug Standard Deviation 854000	—	—
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	19800000 nanogram equivalent of free drug Standard Deviation 1010000	22300000 nanogram equivalent of free drug Standard Deviation 966000	—	—
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	20700000 nanogram equivalent of free drug Standard Deviation 719000	23500000 nanogram equivalent of free drug Standard Deviation 949000	—	—
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	20700000 nanogram equivalent of free drug Standard Deviation 712000	23500000 nanogram equivalent of free drug Standard Deviation 952000	—	—
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	6980 nanogram equivalent of free drug Standard Deviation 17100	982000 nanogram equivalent of free drug Standard Deviation 140000	—	—
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	11600000 nanogram equivalent of free drug Standard Deviation 5790000	13400000 nanogram equivalent of free drug Standard Deviation 5640000	—	—
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	18100000 nanogram equivalent of free drug Standard Deviation 1620000	20300000 nanogram equivalent of free drug Standard Deviation 1340000	—	—
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	18900000 nanogram equivalent of free drug Standard Deviation 1110000	21200000 nanogram equivalent of free drug Standard Deviation 920000	—	—
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	19000000 nanogram equivalent of free drug Standard Deviation 1120000	21300000 nanogram equivalent of free drug Standard Deviation 932000	—	—
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	19100000 nanogram equivalent of free drug Standard Deviation 1110000	21500000 nanogram equivalent of free drug Standard Deviation 934000	—	—
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	19300000 nanogram equivalent of free drug Standard Deviation 1060000	21600000 nanogram equivalent of free drug Standard Deviation 894000	—	—
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	19300000 nanogram equivalent of free drug Standard Deviation 1070000	21700000 nanogram equivalent of free drug Standard Deviation 893000	—	—
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	19500000 nanogram equivalent of free drug Standard Deviation 1050000	21900000 nanogram equivalent of free drug Standard Deviation 878000	—	—
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	19800000 nanogram equivalent of free drug Standard Deviation 969000	22400000 nanogram equivalent of free drug Standard Deviation 922000	—	—
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	20200000 nanogram equivalent of free drug Standard Deviation 742000	22900000 nanogram equivalent of free drug Standard Deviation 825000	—	—
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	20300000 nanogram equivalent of free drug Standard Deviation 733000	23000000 nanogram equivalent of free drug Standard Deviation 847000	—	—

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Part 1: [14C]-GDC-9545 - Urine n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine samples. 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.	Part 1: [14C]-GDC-9545 - Feces n=6 Participants This analysis group represents the total radioactivity recovered from the participants' fecal samples. 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.	Part 1: [14C]-GDC-9545 - Total (Urine and Feces) n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine and feces samples combined. 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	Part 2: GDC-9545/F18 Capsule (Treatment D) This safety analysis set includes all participants in Part 2 of the study during the treatment period in which they received a single dose of Treatment D: GDC-9545/F18 capsule, 30 mg, administered orally with approximately 240 mL water following an overnight fast of a minimum of 10 hours.	Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) This safety analysis set includes all participants in Part 2 who received the three planned doses of GDC-9545 (Treatments B, C, and D) and spans all three treatment periods. In Part 2 of the study, participants were randomly allocated to one of two treatment sequences: Treatments BCD or BDC. In each of the three treatment periods, participants received a single 30 mg dose of GDC-9545 in the fasted state; GDC-9545 was administered as one of three possible formulations. There was a minimum treatment-free washout period of 10 days between each study drug administration.
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: 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	3.191 Percentage of radioactive dose Standard Deviation 0.454	—	—
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	6.428 Percentage of radioactive dose Standard Deviation 10.516	7.759 Percentage of radioactive dose Standard Deviation 10.575	—	—
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	12.603 Percentage of radioactive dose Standard Deviation 13.735	13.390 Percentage of radioactive dose Standard Deviation 13.639	—	—
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	18.625 Percentage of radioactive dose Standard Deviation 14.351	19.191 Percentage of radioactive dose Standard Deviation 14.234	—	—
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	7.565 Percentage of radioactive dose Standard Deviation 8.420	7.871 Percentage of radioactive dose Standard Deviation 8.510	—	—
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	3.848 Percentage of radioactive dose Standard Deviation 2.905	4.030 Percentage of radioactive dose Standard Deviation 2.941	—	—
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	1.471 Percentage of radioactive dose Standard Deviation 1.159	1.647 Percentage of radioactive dose Standard Deviation 1.145	—	—
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	1.424 Percentage of radioactive dose Standard Deviation 1.937	1.586 Percentage of radioactive dose Standard Deviation 1.961	—	—
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	1.377 Percentage of radioactive dose Standard Deviation 1.134	1.492 Percentage of radioactive dose Standard Deviation 1.164	—	—
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	1.528 Percentage of radioactive dose Standard Deviation 2.056	1.626 Percentage of radioactive dose Standard Deviation 2.077	—	—
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	0.612 Percentage of radioactive dose Standard Deviation 0.518	0.687 Percentage of radioactive dose Standard Deviation 0.527	—	—
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	0.207 Percentage of radioactive dose Standard Deviation 0.214	0.289 Percentage of radioactive dose Standard Deviation 0.218	—	—
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	0.517 Percentage of radioactive dose Standard Deviation 0.224	0.583 Percentage of radioactive dose Standard Deviation 0.230	—	—
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	1.178 Percentage of radioactive dose Standard Deviation 0.963	1.601 Percentage of radioactive dose Standard Deviation 0.868	—	—
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	0.289 Percentage of radioactive dose Standard Deviation 0.230	0.337 Percentage of radioactive dose Standard Deviation 0.235	—	—
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	0.158 Percentage of radioactive dose Standard Deviation 0.098	0.201 Percentage of radioactive dose Standard Deviation 0.104	—	—
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: 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	2.932 Percentage of radioactive dose Standard Deviation 2.423	3.352 Percentage of radioactive dose Standard Deviation 2.472	—	—
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	2.379 Percentage of radioactive dose Standard Deviation 3.280	2.469 Percentage of radioactive dose Standard Deviation 3.319	—	—
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	0.644 Percentage of radioactive dose Standard Deviation 0.580	0.734 Percentage of radioactive dose Standard Deviation 0.608	—	—
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	0.396 Percentage of radioactive dose Standard Deviation 0.310	0.453 Percentage of radioactive dose Standard Deviation 0.314	—	—
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	0.225 Percentage of radioactive dose Standard Deviation 0.164	0.292 Percentage of radioactive dose Standard Deviation 0.166	—	—
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	0.239 Percentage of radioactive dose Standard Deviation 0.175	0.295 Percentage of radioactive dose Standard Deviation 0.182	—	—
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 0.010	0.266 Percentage of radioactive dose Standard Deviation 0.146	0.319 Percentage of radioactive dose Standard Deviation 0.150	—	—
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	0.993 Percentage of radioactive dose Standard Deviation 0.889	1.808 Percentage of radioactive dose Standard Deviation 0.518	—	—
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	0.144 Percentage of radioactive dose Standard Deviation 0.158	0.197 Percentage of radioactive dose Standard Deviation 0.168	—	—
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 0.050	1.339 Percentage of radioactive dose Standard Deviation 0.945	1.612 Percentage of radioactive dose Standard Deviation 0.974	—	—

PRIMARY outcome

Timeframe: 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).

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).

Outcome measures

Outcome measures
Measure	Part 1: [14C]-GDC-9545 - Urine n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine samples. 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.	Part 1: [14C]-GDC-9545 - Feces n=6 Participants This analysis group represents the total radioactivity recovered from the participants' fecal samples. 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.	Part 1: [14C]-GDC-9545 - Total (Urine and Feces) n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine and feces samples combined. 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	Part 2: GDC-9545/F18 Capsule (Treatment D) This safety analysis set includes all participants in Part 2 of the study during the treatment period in which they received a single dose of Treatment D: GDC-9545/F18 capsule, 30 mg, administered orally with approximately 240 mL water following an overnight fast of a minimum of 10 hours.	Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) This safety analysis set includes all participants in Part 2 who received the three planned doses of GDC-9545 (Treatments B, C, and D) and spans all three treatment periods. In Part 2 of the study, participants were randomly allocated to one of two treatment sequences: Treatments BCD or BDC. In each of the three treatment periods, participants received a single 30 mg dose of GDC-9545 in the fasted state; GDC-9545 was administered as one of three possible formulations. There was a minimum treatment-free washout period of 10 days between each study drug administration.
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	0.023 Percentage of radioactive dose Standard Deviation 0.056	3.191 Percentage of radioactive dose Standard Deviation 0.454	—	—
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 0.700	19.054 Percentage of radioactive dose Standard Deviation 15.718	24.340 Percentage of radioactive dose Standard Deviation 15.443	—	—
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 0.850	37.679 Percentage of radioactive dose Standard Deviation 18.821	43.532 Percentage of radioactive dose Standard Deviation 18.320	—	—
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	40.611 Percentage of radioactive dose Standard Deviation 17.941	46.884 Percentage of radioactive dose Standard Deviation 17.339	—	—
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	52.024 Percentage of radioactive dose Standard Deviation 8.919	58.785 Percentage of radioactive dose Standard Deviation 8.143	—	—
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	53.495 Percentage of radioactive dose Standard Deviation 9.231	60.432 Percentage of radioactive dose Standard Deviation 8.410	—	—
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	54.919 Percentage of radioactive dose Standard Deviation 8.629	62.018 Percentage of radioactive dose Standard Deviation 7.723	—	—
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	57.298 Percentage of radioactive dose Standard Deviation 5.922	64.487 Percentage of radioactive dose Standard Deviation 4.999	—	—
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	58.676 Percentage of radioactive dose Standard Deviation 5.269	65.979 Percentage of radioactive dose Standard Deviation 4.345	—	—
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	60.848 Percentage of radioactive dose Standard Deviation 3.784	68.339 Percentage of radioactive dose Standard Deviation 3.055	—	—
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	61.459 Percentage of radioactive dose Standard Deviation 3.615	69.026 Percentage of radioactive dose Standard Deviation 2.990	—	—
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	61.666 Percentage of radioactive dose Standard Deviation 3.645	69.315 Percentage of radioactive dose Standard Deviation 3.029	—	—
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	62.183 Percentage of radioactive dose Standard Deviation 3.623	69.898 Percentage of radioactive dose Standard Deviation 3.035	—	—
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	62.579 Percentage of radioactive dose Standard Deviation 3.453	70.351 Percentage of radioactive dose Standard Deviation 2.905	—	—
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	64.302 Percentage of radioactive dose Standard Deviation 3.285	73.065 Percentage of radioactive dose Standard Deviation 2.673	—	—
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	64.446 Percentage of radioactive dose Standard Deviation 3.150	73.262 Percentage of radioactive dose Standard Deviation 2.540	—	—
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	65.913 Percentage of radioactive dose Standard Deviation 2.383	75.200 Percentage of radioactive dose Standard Deviation 2.365	—	—
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	67.410 Percentage of radioactive dose Standard Deviation 2.313	77.012 Percentage of radioactive dose Standard Deviation 2.794	—	—
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 0.570	6.451 Percentage of radioactive dose Standard Deviation 10.500	10.950 Percentage of radioactive dose Standard Deviation 10.498	—	—
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	48.176 Percentage of radioactive dose Standard Deviation 10.145	54.755 Percentage of radioactive dose Standard Deviation 9.345	—	—
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	60.204 Percentage of radioactive dose Standard Deviation 4.176	67.605 Percentage of radioactive dose Standard Deviation 3.358	—	—
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	62.804 Percentage of radioactive dose Standard Deviation 3.463	70.643 Percentage of radioactive dose Standard Deviation 2.903	—	—
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	63.043 Percentage of radioactive dose Standard Deviation 3.346	70.938 Percentage of radioactive dose Standard Deviation 2.774	—	—
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	63.309 Percentage of radioactive dose Standard Deviation 3.408	71.257 Percentage of radioactive dose Standard Deviation 2.853	—	—
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	65.624 Percentage of radioactive dose Standard Deviation 2.412	74.863 Percentage of radioactive dose Standard Deviation 2.281	—	—
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	67.252 Percentage of radioactive dose Standard Deviation 2.336	76.812 Percentage of radioactive dose Standard Deviation 2.771	—	—

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part 1: [14C]-GDC-9545 - Urine n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine samples. 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.	Part 1: [14C]-GDC-9545 - Feces n=6 Participants This analysis group represents the total radioactivity recovered from the participants' fecal samples. 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.	Part 1: [14C]-GDC-9545 - Total (Urine and Feces) n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine and feces samples combined. 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	Part 2: GDC-9545/F18 Capsule (Treatment D) This safety analysis set includes all participants in Part 2 of the study during the treatment period in which they received a single dose of Treatment D: GDC-9545/F18 capsule, 30 mg, administered orally with approximately 240 mL water following an overnight fast of a minimum of 10 hours.	Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) This safety analysis set includes all participants in Part 2 who received the three planned doses of GDC-9545 (Treatments B, C, and D) and spans all three treatment periods. In Part 2 of the study, participants were randomly allocated to one of two treatment sequences: Treatments BCD or BDC. In each of the three treatment periods, participants received a single 30 mg dose of GDC-9545 in the fasted state; GDC-9545 was administered as one of three possible formulations. There was a minimum treatment-free washout period of 10 days between each study drug administration.
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	124 nanogram per millilitre (ng/mL) Geometric Coefficient of Variation 21.4	88.0 nanogram per millilitre (ng/mL) Geometric Coefficient of Variation 25.8	—	—

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part 1: [14C]-GDC-9545 - Urine n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine samples. 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.	Part 1: [14C]-GDC-9545 - Feces n=6 Participants This analysis group represents the total radioactivity recovered from the participants' fecal samples. 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.	Part 1: [14C]-GDC-9545 - Total (Urine and Feces) n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine and feces samples combined. 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	Part 2: GDC-9545/F18 Capsule (Treatment D) This safety analysis set includes all participants in Part 2 of the study during the treatment period in which they received a single dose of Treatment D: GDC-9545/F18 capsule, 30 mg, administered orally with approximately 240 mL water following an overnight fast of a minimum of 10 hours.	Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) This safety analysis set includes all participants in Part 2 who received the three planned doses of GDC-9545 (Treatments B, C, and D) and spans all three treatment periods. In Part 2 of the study, participants were randomly allocated to one of two treatment sequences: Treatments BCD or BDC. In each of the three treatment periods, participants received a single 30 mg dose of GDC-9545 in the fasted state; GDC-9545 was administered as one of three possible formulations. There was a minimum treatment-free washout period of 10 days between each study drug administration.
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 Interval 2.0 to 5.0	5.00 Hours Interval 2.0 to 5.0	5.00 Hours Interval 2.5 to 5.0	—	—

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part 1: [14C]-GDC-9545 - Urine n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine samples. 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.	Part 1: [14C]-GDC-9545 - Feces n=6 Participants This analysis group represents the total radioactivity recovered from the participants' fecal samples. 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.	Part 1: [14C]-GDC-9545 - Total (Urine and Feces) n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine and feces samples combined. 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	Part 2: GDC-9545/F18 Capsule (Treatment D) This safety analysis set includes all participants in Part 2 of the study during the treatment period in which they received a single dose of Treatment D: GDC-9545/F18 capsule, 30 mg, administered orally with approximately 240 mL water following an overnight fast of a minimum of 10 hours.	Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) This safety analysis set includes all participants in Part 2 who received the three planned doses of GDC-9545 (Treatments B, C, and D) and spans all three treatment periods. In Part 2 of the study, participants were randomly allocated to one of two treatment sequences: Treatments BCD or BDC. In each of the three treatment periods, participants received a single 30 mg dose of GDC-9545 in the fasted state; GDC-9545 was administered as one of three possible formulations. There was a minimum treatment-free washout period of 10 days between each study drug administration.
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 nanogramhours per milliltre (ngh/mL) Geometric Coefficient of Variation 32.2	3370 nanogramhours per milliltre (ngh/mL) Geometric Coefficient of Variation 24.4	2530 nanogramhours per milliltre (ngh/mL) Geometric Coefficient of Variation 22.5	—	—

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part 1: [14C]-GDC-9545 - Urine n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine samples. 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.	Part 1: [14C]-GDC-9545 - Feces n=6 Participants This analysis group represents the total radioactivity recovered from the participants' fecal samples. 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.	Part 1: [14C]-GDC-9545 - Total (Urine and Feces) n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine and feces samples combined. 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	Part 2: GDC-9545/F18 Capsule (Treatment D) This safety analysis set includes all participants in Part 2 of the study during the treatment period in which they received a single dose of Treatment D: GDC-9545/F18 capsule, 30 mg, administered orally with approximately 240 mL water following an overnight fast of a minimum of 10 hours.	Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) This safety analysis set includes all participants in Part 2 who received the three planned doses of GDC-9545 (Treatments B, C, and D) and spans all three treatment periods. In Part 2 of the study, participants were randomly allocated to one of two treatment sequences: Treatments BCD or BDC. In each of the three treatment periods, participants received a single 30 mg dose of GDC-9545 in the fasted state; GDC-9545 was administered as one of three possible formulations. There was a minimum treatment-free washout period of 10 days between each study drug administration.
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 nanogramhours per milliltre (ngh/mL) Geometric Coefficient of Variation 43.8	4160 nanogramhours per milliltre (ngh/mL) Geometric Coefficient of Variation 40.3	3280 nanogramhours per milliltre (ngh/mL) Geometric Coefficient of Variation 40.9	—	—

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part 1: [14C]-GDC-9545 - Urine n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine samples. 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.	Part 1: [14C]-GDC-9545 - Feces n=3 Participants This analysis group represents the total radioactivity recovered from the participants' fecal samples. 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.	Part 1: [14C]-GDC-9545 - Total (Urine and Feces) This analysis group represents the total radioactivity recovered from the participants' urine and feces samples combined. 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	Part 2: GDC-9545/F18 Capsule (Treatment D) This safety analysis set includes all participants in Part 2 of the study during the treatment period in which they received a single dose of Treatment D: GDC-9545/F18 capsule, 30 mg, administered orally with approximately 240 mL water following an overnight fast of a minimum of 10 hours.	Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) This safety analysis set includes all participants in Part 2 who received the three planned doses of GDC-9545 (Treatments B, C, and D) and spans all three treatment periods. In Part 2 of the study, participants were randomly allocated to one of two treatment sequences: Treatments BCD or BDC. In each of the three treatment periods, participants received a single 30 mg dose of GDC-9545 in the fasted state; GDC-9545 was administered as one of three possible formulations. There was a minimum treatment-free washout period of 10 days between each study drug administration.
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 nanogramhours per milliltre (ngh/mL) Geometric Coefficient of Variation 43.2	6480 nanogramhours per milliltre (ngh/mL) Geometric Coefficient of Variation 39.2	—	—	—

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part 1: [14C]-GDC-9545 - Urine n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine samples. 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.	Part 1: [14C]-GDC-9545 - Feces n=6 Participants This analysis group represents the total radioactivity recovered from the participants' fecal samples. 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.	Part 1: [14C]-GDC-9545 - Total (Urine and Feces) n=3 Participants This analysis group represents the total radioactivity recovered from the participants' urine and feces samples combined. 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	Part 2: GDC-9545/F18 Capsule (Treatment D) This safety analysis set includes all participants in Part 2 of the study during the treatment period in which they received a single dose of Treatment D: GDC-9545/F18 capsule, 30 mg, administered orally with approximately 240 mL water following an overnight fast of a minimum of 10 hours.	Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) This safety analysis set includes all participants in Part 2 who received the three planned doses of GDC-9545 (Treatments B, C, and D) and spans all three treatment periods. In Part 2 of the study, participants were randomly allocated to one of two treatment sequences: Treatments BCD or BDC. In each of the three treatment periods, participants received a single 30 mg dose of GDC-9545 in the fasted state; GDC-9545 was administered as one of three possible formulations. There was a minimum treatment-free washout period of 10 days between each study drug administration.
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	48.4 Hours Geometric Coefficient of Variation 29.4	50.8 Hours Geometric Coefficient of Variation 46.4	—	—

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part 1: [14C]-GDC-9545 - Urine n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine samples. 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.	Part 1: [14C]-GDC-9545 - Feces n=6 Participants This analysis group represents the total radioactivity recovered from the participants' fecal samples. 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.	Part 1: [14C]-GDC-9545 - Total (Urine and Feces) n=3 Participants This analysis group represents the total radioactivity recovered from the participants' urine and feces samples combined. 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	Part 2: GDC-9545/F18 Capsule (Treatment D) This safety analysis set includes all participants in Part 2 of the study during the treatment period in which they received a single dose of Treatment D: GDC-9545/F18 capsule, 30 mg, administered orally with approximately 240 mL water following an overnight fast of a minimum of 10 hours.	Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) This safety analysis set includes all participants in Part 2 who received the three planned doses of GDC-9545 (Treatments B, C, and D) and spans all three treatment periods. In Part 2 of the study, participants were randomly allocated to one of two treatment sequences: Treatments BCD or BDC. In each of the three treatment periods, participants received a single 30 mg dose of GDC-9545 in the fasted state; GDC-9545 was administered as one of three possible formulations. There was a minimum treatment-free washout period of 10 days between each study drug administration.
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	0.0143 1/Hours Geometric Coefficient of Variation 29.4	0.0136 1/Hours Geometric Coefficient of Variation 46.4	—	—

PRIMARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part 1: [14C]-GDC-9545 - Urine n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine samples. 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.	Part 1: [14C]-GDC-9545 - Feces This analysis group represents the total radioactivity recovered from the participants' fecal samples. 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.	Part 1: [14C]-GDC-9545 - Total (Urine and Feces) This analysis group represents the total radioactivity recovered from the participants' urine and feces samples combined. 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	Part 2: GDC-9545/F18 Capsule (Treatment D) This safety analysis set includes all participants in Part 2 of the study during the treatment period in which they received a single dose of Treatment D: GDC-9545/F18 capsule, 30 mg, administered orally with approximately 240 mL water following an overnight fast of a minimum of 10 hours.	Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) This safety analysis set includes all participants in Part 2 who received the three planned doses of GDC-9545 (Treatments B, C, and D) and spans all three treatment periods. In Part 2 of the study, participants were randomly allocated to one of two treatment sequences: Treatments BCD or BDC. In each of the three treatment periods, participants received a single 30 mg dose of GDC-9545 in the fasted state; GDC-9545 was administered as one of three possible formulations. There was a minimum treatment-free washout period of 10 days between each study drug administration.
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 outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Part 1: [14C]-GDC-9545 - Urine n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine samples. 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.	Part 1: [14C]-GDC-9545 - Feces This analysis group represents the total radioactivity recovered from the participants' fecal samples. 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.	Part 1: [14C]-GDC-9545 - Total (Urine and Feces) This analysis group represents the total radioactivity recovered from the participants' urine and feces samples combined. 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	Part 2: GDC-9545/F18 Capsule (Treatment D) This safety analysis set includes all participants in Part 2 of the study during the treatment period in which they received a single dose of Treatment D: GDC-9545/F18 capsule, 30 mg, administered orally with approximately 240 mL water following an overnight fast of a minimum of 10 hours.	Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) This safety analysis set includes all participants in Part 2 who received the three planned doses of GDC-9545 (Treatments B, C, and D) and spans all three treatment periods. In Part 2 of the study, participants were randomly allocated to one of two treatment sequences: Treatments BCD or BDC. In each of the three treatment periods, participants received a single 30 mg dose of GDC-9545 in the fasted state; GDC-9545 was administered as one of three possible formulations. There was a minimum treatment-free washout period of 10 days between each study drug administration.
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 outcome

Timeframe: 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).

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).

Outcome measures

Outcome measures
Measure	Part 1: [14C]-GDC-9545 - Urine n=6 Participants This analysis group represents the total radioactivity recovered from the participants' urine samples. 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.	Part 1: [14C]-GDC-9545 - Feces n=6 Participants This analysis group represents the total radioactivity recovered from the participants' fecal samples. 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.	Part 1: [14C]-GDC-9545 - Total (Urine and Feces) This analysis group represents the total radioactivity recovered from the participants' urine and feces samples combined. 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	Part 2: GDC-9545/F18 Capsule (Treatment D) This safety analysis set includes all participants in Part 2 of the study during the treatment period in which they received a single dose of Treatment D: GDC-9545/F18 capsule, 30 mg, administered orally with approximately 240 mL water following an overnight fast of a minimum of 10 hours.	Part 2: Overall: Any GDC-9545 (Treatments B, C, or D) This safety analysis set includes all participants in Part 2 who received the three planned doses of GDC-9545 (Treatments B, C, and D) and spans all three treatment periods. In Part 2 of the study, participants were randomly allocated to one of two treatment sequences: Treatments BCD or BDC. In each of the three treatment periods, participants received a single 30 mg dose of GDC-9545 in the fasted state; GDC-9545 was administered as one of three possible formulations. There was a minimum treatment-free washout period of 10 days between each study drug administration.
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	48.4 nanogram equivalent of free drug/mL Geometric Coefficient of Variation 32.9	—	—	—
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	74.3 nanogram equivalent of free drug/mL Geometric Coefficient of Variation 26.3	—	—	—
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	76.7 nanogram equivalent of free drug/mL Geometric Coefficient of Variation 27.2	—	—	—
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	64.8 nanogram equivalent of free drug/mL Geometric Coefficient of Variation 22.2	—	—	—
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	52.3 nanogram equivalent of free drug/mL Geometric Coefficient of Variation 20.8	—	—	—
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	36.0 nanogram equivalent of free drug/mL Geometric Coefficient of Variation 26.2	—	—	—
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	9.97 nanogram equivalent of free drug/mL Geometric Coefficient of Variation 74.9	—	—	—
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	11.5 nanogram equivalent of free drug/mL Geometric Coefficient of Variation 64.4	—	—	—
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 46.0	7.44 nanogram equivalent of free drug/mL Geometric Coefficient of Variation 49.2	—	—	—
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	66.7 nanogram equivalent of free drug/mL Geometric Coefficient of Variation 24.8	—	—	—
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	76.3 nanogram equivalent of free drug/mL Geometric Coefficient of Variation 24.9	—	—	—
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	74.4 nanogram equivalent of free drug/mL Geometric Coefficient of Variation 21.9	—	—	—
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	85.9 nanogram equivalent of free drug/mL Geometric Coefficient of Variation 22.3	—	—	—
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	70.4 nanogram equivalent of free drug/mL Geometric Coefficient of Variation 19.5	—	—	—
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	24.6 nanogram equivalent of free drug/mL Geometric Coefficient of Variation 26.3	—	—	—
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 31.0	18.7 nanogram equivalent of free drug/mL Geometric Coefficient of Variation 25.0	—	—	—
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	7.92 nanogram equivalent of free drug/mL Geometric Coefficient of Variation 61.0	—	—	—

PRIMARY outcome

Timeframe: 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.

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).