A Pharmacokinetic Study of [14C]-GDC-0810 After Single Oral Administration in Healthy Female Participants

Study Overview
=================
Brief Summary
-----------------
This is an open-label, non-randomized study to determine the excretion kinetics and mass balance of GDC-0810, and to determine metabolites present in blood, feces, and urine in healthy participants following a single 300-milligram (mg) oral dose of GDC-0810 containing approximately 100 microcuries of [14C] labeled GDC-0810 using conventional absorption, metabolism, and excretion (AME) methodology. The entire duration of the study is up to approximately 8 weeks.

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Drug: [14C]-GDC-0810


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy participants with non-child bearing potential, non-pregnant, non-lactating and either post-menopausal or surgically sterile. Negative pregnancy test result at Screening and at Day -1. Body mass index of 18.5 to 29.9 kilogram per square meter. Healthy condition documented with no clinically significant findings from laboratory evaluations, medical history, 12-lead electrocardiograms, and vital signs. Exclusion Criteria: Significant history of metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastric, neurological, or psychiatric disorder. History of significant hypersensitivity or allergy to any drug. Uncontrolled hypothyroidism. History or presence of clinically significant abnormal electrocardiogram. History of venous thrombosis, endometrial disorders, thrombophilic condition, inflammatory bowel disease, chronic diarrhoea, active or latent tuberculosis, and Gilbert's syndrome. Major surgical procedure or significant traumatic injury within 3 months prior to study participation. Participation in more than one other radiolabeled investigational drug study within 12 months prior to Check-in (Day -1). Exposure to significant radiation occuring within 12 months prior to Check-in (Day -1). Any acute or chronic condition that would limit the participant's ability to participate in the clinical study. Failure to satisfy the Investigator of fitness to participate for any other reason.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GDC-0810<br>GDC-0810 300-mg dose administered as oral solution, containing approximately 100 microcuries of [14C]-labeled GDC-0810. | Drug: [14C]-GDC-0810<br>* Participants will receive a single 300-mg dose of GDC-0810 containing approximately 100 microcuries of [14C]-labeled GDC-0810 on Day 1.<br>* Other names: ARN-810; RO7056118;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax for [14C]-GDC-0810 |  | Pre-dose (0 hr), 10, 30, 45 mins, 1, 2, 3, 4, 6, 8, 12 hrs post-dose on Day 1, Day 2 (24, 36 hrs post-dose), Days 3, 4, 5, 6, and 7 post-dose | 
| Time to maximum concentration (Tmax) for GDC-0810 |  | Pre-dose (0 hr), 10, 30, 45 mins, 1, 2, 3, 4, 6, 8, 12 hrs post-dose on Day 1, Day 2 (24, 36 hrs post-dose), Days 3, 4, 5, 6, and 7 post-dose | 
| Tmax for [14C]-GDC-0810 |  | Pre-dose (0 hr), 10, 30, 45 mins, 1, 2, 3, 4, 6, 8, 12 hrs post-dose on Day 1, Day 2 (24, 36 hrs post-dose), Days 3, 4, 5, 6, and 7 post-dose | 
| Area under the Concentration-Time Curve (AUC) from Hour 0 to Last Measurable Concentration (AUC0-t) for GDC-0810 |  | Pre-dose (0 hr), 10, 30, 45 mins, 1, 2, 3, 4, 6, 8, 12 hrs post-dose on Day 1, Day 2 (24, 36 hrs post-dose), Days 3, 4, 5, 6, and 7 post-dose | 
| AUC0-t for [14C]-GDC-0810 |  | Pre-dose (0 hr), 10, 30, 45 mins, 1, 2, 3, 4, 6, 8, 12 hrs post-dose on Day 1, Day 2 (24, 36 hrs post-dose), Days 3, 4, 5, 6, and 7 post-dose | 
| AUC Extrapolated to Infinity (AUC0-inf) for GDC-0810 |  | Pre-dose (0 hr), 10, 30, 45 mins, 1, 2, 3, 4, 6, 8, 12 hrs post-dose on Day 1, Day 2 (24, 36 hrs post-dose), Days 3, 4, 5, 6, and 7 post-dose | 
| AUC0-inf for [14C]-GDC-0810 |  | Pre-dose (0 hr), 10, 30, 45 mins, 1, 2, 3, 4, 6, 8, 12 hrs post-dose on Day 1, Day 2 (24, 36 hrs post-dose), Days 3, 4, 5, 6, and 7 post-dose | 
| Apparent Terminal Rate Elimination Constant for GDC-0810 |  | Pre-dose (0 hr), 10, 30, 45 mins, 1, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1, Day 2 (24, 36 hours post-dose), Days 3, 4, 5, 6, and 7 post-dose | 
| Maximum Observed Concentration (Cmax) for GDC-0810 |  | Pre-dose [0 hour (hr)], 10, 30, 45 minutes (min), 1, 2, 3, 4, 6, 8, 12 hrs post-dose on Day 1, Day 2 (24, 36 hrs post-dose), Days 3, 4, 5, 6, and 7 post-dose | 
| Apparent Terminal Elimination Constant for [14C]-GDC-0810 |  | Pre-dose (0 hr), 10, 30, 45 mins, 1, 2, 3, 4, 6, 8, 12 hours post-dose on Day 1, Day 2 (24, 36 hours post-dose), Days 3, 4, 5, 6, and 7 post-dose | 
| Apparent Terminal Elimination Half-Life (t1/2) for GDC-0810 |  | Pre-dose (0 hr), 10, 30, 45 mins, 1, 2, 3, 4, 6, 8, 12 hrs post-dose on Day 1, Day 2 (24, 36 hrs post-dose), Days 3, 4, 5, 6, and 7 post-dose | 
| t1/2 for [14C]-GDC-0810 |  | Pre-dose (0 hr), 10, 30, 45 mins, 1, 2, 3, 4, 6, 8, 12 hrs post-dose on Day 1, Day 2 (24, 36 hrs post-dose), Days 3, 4, 5, 6, and 7 post-dose | 
| Apparent Oral Clearance (CL/F) for GDC-0810 |  | Pre-dose (0 hr), 10, 30, 45 mins, 1, 2, 3, 4, 6, 8, 12 hrs post-dose on Day 1, Day 2 (24, 36 hrs post-dose), Days 3, 4, 5, 6, and 7 post-dose | 
| Apparent Volume of Distribution (Vz/F) for GDC-0810 |  | Pre-dose (0 hr), 10, 30, 45 mins, 1, 2, 3, 4, 6, 8, 12 hrs post-dose on Day 1, Day 2 (24, 36 hrs post-dose), Days 3, 4, 5, 6, and 7 post-dose | 
| Amount of Total Radioactivity Excreted in Urine Over the Sampling Interval (Aeu) for [14C]-GDC-0810 (Whenever Possible) |  | Pre-dose (0 hr), 0 to 12 and 12 to 24 hrs post-dose on Day 1, Days 2 (24 to 48 hrs), 3 (48 to 72 hrs), 4 (72 to 96 hrs), 5 (96 to 120 hrs), 6 (120 to 144 hrs) post-dose, and at 24-hr interval from Days 7-14 or until clinical discharge criteria met | 
| Cumulative Aeu (Total Aeu) of [14C]-GDC-0810 (Whenever Possible) |  | Pre-dose (0 hr), 0 to 12 and 12 to 24 hrs post-dose on Day 1, Days 2 (24 to 48 hrs), 3 (48 to 72 hrs), 4 (72 to 96 hrs), 5 (96 to 120 hrs), 6 (120 to 144 hrs) post-dose, and at 24-hr interval from Days 7-14 or until clinical discharge criteria met | 
| Renal Clearance (CLR) for [14C]-GDC-0810 (Whenever Possible) |  | Pre-dose (0 hr), 0 to 12 and 12 to 24 hrs post-dose on Day 1, Days 2 (24 to 48 hrs), 3 (48 to 72 hrs), 4 (72 to 96 hrs), 5 (96 to 120 hrs), 6 (120 to 144 hrs) post-dose, and at 24-hr interval from Days 7-14 or until clinical discharge criteria met | 
| Percent of Total radioactivity Excreted in Urine Over Sampling (% Feu) for [14C]-GDC-0810 (Whenever Possible) |  | Pre-dose (0 hr), 0 to 12 and 12 to 24 hrs post-dose on Day 1, Days 2 (24 to 48 hrs), 3 (48 to 72 hrs), 4 (72 to 96 hrs), 5 (96 to 120 hrs), 6 (120 to 144 hrs) post-dose, and at 24-hr interval from Days 7-14 or until clinical discharge criteria met | 
| Cumulative % Feu (Total % Feu) for [14C]-GDC-0810 (Whenever Possible) |  | Pre-dose (0 hr), 0 to 12 and 12 to 24 hrs post-dose on Day 1, Days 2 (24 to 48 hrs), 3 (48 to 72 hrs), 4 (72 to 96 hrs), 5 (96 to 120 hrs), 6 (120 to 144 hrs) post-dose, and at 24-hr interval from Days 7-14 or until clinical discharge criteria met | 
| Amount of Total Radioactivity Excreted in Feces Over the Sampling Interval (Aef) for [14C]-GDC-0810 (Whenever Possible) |  | Pre-dose (0 hr), 0 to 24 hrs post-dose on Day 1, Days 2 (24 to 48 hrs), 3 (48 to 72 hrs), 4 (72 to 96 hrs), 5 (96 to 120 hrs), 6 (120 to 144 hrs) post-dose, and at 24-hr interval from Days 7-14 post-dose or until clinical discharge criteria met | 
| Cumulative Aef (Total Aef) for [14C]-GDC-0810 (Whenever Possible) |  | Pre-dose (0 hr), 0 to 24 hrs post-dose on Day 1, Days 2 (24 to 48 hrs), 3 (48 to 72 hrs), 4 (72 to 96 hrs), 5 (96 to 120 hrs), 6 (120 to 144 hrs) post-dose, and at 24-hr interval from Days 7-14 post-dose or until clinical discharge criteria met | 
| Percent of Total radioactivity Excreted in Feces Over Sampling (% Fef) for [14C]-GDC-0810 (Whenever Possible) |  | Pre-dose (0 hr), 0 to 24 hrs post-dose on Day 1, Days 2 (24 to 48 hrs), 3 (48 to 72 hrs), 4 (72 to 96 hrs), 5 (96 to 120 hrs), 6 (120 to 144 hrs) post-dose, and at 24-hr interval from Days 7-14 post-dose or until clinical discharge criteria met | 
| Cumulative % Fef (Total % Fef) for [14C]-GDC-0810 (Whenever Possible) |  | Pre-dose (0 hr), 0 to 24 hrs post-dose on Day 1, Days 2 (24 to 48 hrs), 3 (48 to 72 hrs), 4 (72 to 96 hrs), 5 (96 to 120 hrs), 6 (120 to 144 hrs) post-dose, and at 24-hr interval from Days 7-14 post-dose or until clinical discharge criteria met |