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

NCT02802670 | Completed Phase 1

• 1 other identifier: GP29916
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (23)

• 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

Study Arms (1)

GDC-0810

EXPERIMENTAL

GDC-0810 300-mg dose administered as oral solution, containing approximately 100 microcuries of \[14C\]-labeled GDC-0810.

Drug: [14C]-GDC-0810

Interventions

[14C]-GDC-0810 DRUG

Participants will receive a single 300-mg dose of GDC-0810 containing approximately 100 microcuries of \[14C\]-labeled GDC-0810 on Day 1.

Also known as: ARN-810; RO7056118

GDC-0810

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (1)

Unknown Facility

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Interventions

3-(4-(2-(2-chloro-4-fluorophenyl)-1-(1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylic acid

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2016
• First Posted: June 16, 2016
• Study Start: May 1, 2016
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: June 16, 2016

Record last verified: 2016-06

Locations

US (1)