Clinical trial NCT02802670: A Pharmacokinetic Study of [14C]-GDC-0810 After Single Oral Administration in Healthy Female Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2016-06-16
Enrollment: 7
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


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.

Primary outcomes:
measure: Cmax for [14C]-GDC-0810
timeFrame: 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
measure: Time to maximum concentration (Tmax) for GDC-0810
timeFrame: 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
measure: Tmax for [14C]-GDC-0810
timeFrame: 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
measure: Area under the Concentration-Time Curve (AUC) from Hour 0 to Last Measurable Concentration (AUC0-t) for GDC-0810
timeFrame: 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
measure: AUC0-t for [14C]-GDC-0810
timeFrame: 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
measure: AUC Extrapolated to Infinity (AUC0-inf) for GDC-0810
timeFrame: 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
measure: AUC0-inf for [14C]-GDC-0810
timeFrame: 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
measure: Apparent Terminal Rate Elimination Constant for GDC-0810
timeFrame: 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
measure: Maximum Observed Concentration (Cmax) for GDC-0810
timeFrame: 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
measure: Apparent Terminal Elimination Constant for [14C]-GDC-0810
timeFrame: 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
measure: Apparent Terminal Elimination Half-Life (t1/2) for GDC-0810
timeFrame: 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
measure: t1/2 for [14C]-GDC-0810
timeFrame: 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
measure: Apparent Oral Clearance (CL/F) for GDC-0810
timeFrame: 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
measure: Apparent Volume of Distribution (Vz/F) for GDC-0810
timeFrame: 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
measure: Amount of Total Radioactivity Excreted in Urine Over the Sampling Interval (Aeu) for [14C]-GDC-0810 (Whenever Possible)
timeFrame: 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
measure: Cumulative Aeu (Total Aeu) of [14C]-GDC-0810 (Whenever Possible)
timeFrame: 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
measure: Renal Clearance (CLR) for [14C]-GDC-0810 (Whenever Possible)
timeFrame: 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
measure: Percent of Total radioactivity Excreted in Urine Over Sampling (% Feu) for [14C]-GDC-0810 (Whenever Possible)
timeFrame: 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
measure: Cumulative % Feu (Total % Feu) for [14C]-GDC-0810 (Whenever Possible)
timeFrame: 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
measure: Amount of Total Radioactivity Excreted in Feces Over the Sampling Interval (Aef) for [14C]-GDC-0810 (Whenever Possible)
timeFrame: 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
measure: Cumulative Aef (Total Aef) for [14C]-GDC-0810 (Whenever Possible)
timeFrame: 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
measure: Percent of Total radioactivity Excreted in Feces Over Sampling (% Fef) for [14C]-GDC-0810 (Whenever Possible)
timeFrame: 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
measure: Cumulative % Fef (Total % Fef) for [14C]-GDC-0810 (Whenever Possible)
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: Madison
country: United States
state: Wisconsin
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: