Healthy VolunteersPhase 1NCT01249118

An Absolute Bioavailability Study in Healthy Participants Comparing Oral to Intravenous Administration of GDC-0973 (Cobimetinib)

A Phase 1 study testing GDC-0973 IV Infusion and GDC-0973 Oral Capsules in people with Healthy Volunteers, run by Genentech, Inc..

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The primary objective of Part 1 of this study is to evaluate the safety and tolerability of the intravenous (IV) dose of GDC-0973. The primary objectives of Part 2 of this study are to evaluate the absolute bioavailability of GDC-0973 and to evaluate the pharmacokinetic (PK) of GDC-0973 following IV and oral… Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers
What is being tested?: GDC-0973 IV Infusion and GDC-0973 Oral Capsules
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 13 participants
Where: No sites listed yet
Study dates: Nov 2010to Jan 2011
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Within body mass index range 18.5 to 29.9 kilograms per square meter (kg/m^2)
In good health, determined by no clinically significant findings from medical history, 12-lead electrocardiogram (ECG), and vital signs
Clinical laboratory evaluations within the reference range for the test laboratory
Negative test for selected drugs of abuse at Screening and at each Check-in
Negative hepatitis panel and anti-hepatitis C virus and negative human immunodeficiency virus (HIV) antibody screens
Healthy males and females of non-child-bearing potential or who agree to use effective contraception

Who cannot join

Significant history or clinical manifestation of any significant metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder
History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance
History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs except that appendectomy, hernia repair, and cholecystectomy will be allowed
History or presence of an abnormal ECG
History of alcoholism or drug addiction prior to period 1 check-in
Use of any tobacco-containing or nicotine-containing products prior to period 1 check-in

Show all 12Show fewer

Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 28 days or 5 half-lives, whichever is longer, prior to period 1 check-in
Use of any prescription medications/products, including proton pump inhibitors, within 14 days prior to period 1 check-in
Poor peripheral venous access
Any acute or chronic condition that would limit the participants ability to complete and/or participate in this clinical study
Female participant is pregnant, lactating, or breastfeeding
Predisposing factors to retinal vein occlusion (RVO)

About this study

Official title: A Phase 1, Single Dose, Randomized, Cross-over Absolute Bioavailability Study in Healthy Subjects Comparing Oral to Intravenous Administration of GDC-0973

Conditions: Healthy Volunteers
Being tested: GDC-0973 IV Infusion, GDC-0973 Oral Capsules

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GDC-0973 IV InfusionDrug
Also called XL518
IV infusion.
GDC-0973 Oral CapsulesDrug
Also called XL518
Oral dose.

Study groups in NCT01249118
Study group	Role	What they receive
Part 1: GDC-0973 IV Infusion First, Then GDC-0973 Capsules	Experimental	Participants will receive single dose of GDC-0973 2 milligrams (mg) IV infusion in first intervention period followed by single dose of GDC-0973 20 mg oral capsules (four 5-mg capsules) in second intervention period. The washout period between each period will be a minimum of 10 days. Receives: Drug: GDC-0973 IV Infusion; Drug: GDC-0973 Oral Capsules
Part 2: GDC-0973 IV Infusion First, Then GDC-0973 Capsules	Experimental	Participants will receive single dose of GDC-0973 2 mg IV infusion in first intervention period followed by single dose of GDC-0973 20 mg oral capsules (four 5-mg capsules) in second intervention period. The washout period between each period will be a minimum of 10 days. Receives: Drug: GDC-0973 IV Infusion; Drug: GDC-0973 Oral Capsules
Part 2: GDC-0973 Capsules First, Then GDC-0973 IV Infusion	Experimental	Participants will receive single dose of GDC-0973 20 mg oral capsules (four 5-mg capsules) in first intervention period followed by single dose of GDC-0973 2 mg IV infusion in second intervention period. The washout period between each period will be a minimum of 10 days. Receives: Drug: GDC-0973 IV Infusion; Drug: GDC-0973 Oral Capsules

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Observed Plasma Concentration (Cmax) of IV and Oral GDC-0973
Measured: Part 2: 0 hours (Hrs) (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Dose Normalized Cmax [Cmax(dn)] of IV and Oral GDC-0973
Cmax(dn) is Cmax divided by dose.
Measured: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Minimum Observed Plasma Trough Concentration (Cmin) of IV and Oral GDC-0973
Measured: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Time to Reach Maximum Observed Plasma Concentration (Tmax) of IV and Oral GDC-0973
Measured: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of IV and Oral GDC-0973
AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t).
Measured: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Dose Normalized AUC (0-t) [AUC (0-t)dn] of IV and Oral GDC-0973
AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t). AUC (0-t)dn is AUC (0-t) divided by dose.
Measured: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of IV and Oral GDC-0973
AUC (0 - ∞)= Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Measured: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Dose Normalized AUC (0 - ∞) [AUC (0 - ∞)dn] of IV and Oral GDC-0973
AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). AUC (0 - ∞)dn is AUC(0 - ∞) divided by dose.
Measured: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Plasma Decay Half-Life (t1/2) of IV and Oral GDC-0973
t1/2 is the time measured for the plasma concentration of GDC-0973 to decrease by one half.
Measured: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Systemic Clearance (CL) of IV GDC-0973
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Measured: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Apparent Oral Clearance (CL/F) of Oral GDC-0973
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modelling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Measured: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Volume of Distribution at Steady State (Vss) of IV GDC-0973
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the apparent volume of distribution at steady-state.
Measured: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose of Day 1
Apparent Volume of Distribution (Vz/F) of Oral GDC-0973
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F is influenced by the fraction absorbed.
Measured: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Absolute Oral Bioavailability (F) of GDC-0973
Absolute oral bioavailability is the amount of drug from a formulation that reaches the systemic circulation relative to an IV dose. F = [AUC (0-∞), oral multiplied by Dose IV] divided by [AUC (0-∞), IV multiplied by Dose oral]. Absolute oral bioavailability is determined for drugs which are administered orally. IV dose is 100% in systemic circulation (dosed directly) and hence no estimation is required.
Measured: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Mean Absorption Time (MAT)
MAT is mean time required for the drug to reach the central compartment. MAT was estimated from the mean resident time (MRT) from oral and IV administration. MAT was calculated as MRT last of oral dose minus MRT last of IV dose. MAT is analyzed when drug is administered orally (only for non-IV routes of administration).
Measured: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Amount of Drug Excreted in the Urine (Aeu) of IV and Oral GDC-0973
The cumulative amount of drug excreted in urine over the entire collection interval of 96 hrs was calculated by adding the Aeu of the intervals 0 to 12, 12 to 24, 24 to 48, 48 to 72, and 72 to 96 hrs where Aeu was calculated by multiplying the urine volume within the collection interval by the associated drug concentration.
Measured: Part 2: 0 to 12, 12 to 24, 24 to 48, 48 to 72, and 72 to 96 Hrs post-dose on Day 1
Renal Clearance (CLR) of IV and Oral GDC-0973
CLR was calculated as Aeu divided by AUC (0 - ∞), where Aeu was amount of drug excreted in urine from time 0 to 96 hrs post-dose and AUC(0 - ∞) was area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity hrs post-dose.
Measured: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1 for plasma; 0 to 12, 12 to 24, 24 to 48, 48 to 72, and 72 to 96 Hrs post-dose for urine
Percent of GDC-0973 Excreted in the Urine (% Excreted) for IV and Oral GDC-0973
% Excreted is the mean percentage of dose recovery in urine and calculated as: (Aeu divided by dose) multiplied by 100, where Aeu was amount of drug excreted in urine from time 0 to 96 hrs post-dose.
Measured: Part 2: 0 to 12, 12 to 24, 24 to 48, 48 to 72, and 72 to 96 Hrs post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2010Jan 2011

First posted29 Nov 2010 (estimated)
Study startNov 2010
Primary completionJan 2011
Study completionJan 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Healthy VolunteersStudies of the same condition, open and under way.
More trials run by Genentech, Inc.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01249118
Sponsor's protocol ID: MEK4952g
Status last verified: Apr 2017
First submitted: 24 Nov 2010
Last updated: 10 May 2017
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 10 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Single Dose, Randomized, Cross-over Absolute Bioavailability Study in Healthy Subjects Comparing Oral to Intravenous Administration of GDC-0973
ClinicalTrials.gov ID: NCT01249118
Acronym / sponsor ID: MEK4952g
Conditions: Healthy Volunteers
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 13 participants (actual)
Lead sponsor: Genentech, Inc.Industry (pharma, biotech, devices)
Study start: Nov 2010
Primary completion: Jan 2011 (actual)
Study completion: Jan 2011 (actual)
First posted: 29 Nov 2010 (estimated)
Results: Posted 6 Feb 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Part 1: GDC-0973 IV Infusion First, Then GDC-0973 Capsules	Experimental	Drug: GDC-0973 IV Infusion, Drug: GDC-0973 Oral CapsulesParticipants will receive single dose of GDC-0973 2 milligrams (mg) IV infusion in first intervention period followed by single dose of GDC-0973 20 mg oral capsules (four 5-mg capsules) in second intervention period. The washout period between each period will be a minimum of 10 days.
Part 2: GDC-0973 IV Infusion First, Then GDC-0973 Capsules	Experimental	Drug: GDC-0973 IV Infusion, Drug: GDC-0973 Oral CapsulesParticipants will receive single dose of GDC-0973 2 mg IV infusion in first intervention period followed by single dose of GDC-0973 20 mg oral capsules (four 5-mg capsules) in second intervention period. The washout period between each period will be a minimum of 10 days.
Part 2: GDC-0973 Capsules First, Then GDC-0973 IV Infusion	Experimental	Drug: GDC-0973 IV Infusion, Drug: GDC-0973 Oral CapsulesParticipants will receive single dose of GDC-0973 20 mg oral capsules (four 5-mg capsules) in first intervention period followed by single dose of GDC-0973 2 mg IV infusion in second intervention period. The washout period between each period will be a minimum of 10 days.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (6 listed)

Within body mass index range 18.5 to 29.9 kilograms per square meter (kg/m^2)
In good health, determined by no clinically significant findings from medical history, 12-lead electrocardiogram (ECG), and vital signs
Clinical laboratory evaluations within the reference range for the test laboratory
Negative test for selected drugs of abuse at Screening and at each Check-in
Negative hepatitis panel and anti-hepatitis C virus and negative human immunodeficiency virus (HIV) antibody screens

Key exclusion criteria (12 listed)

Significant history or clinical manifestation of any significant metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder
History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance
History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs except that appendectomy, hernia repair, and cholecystectomy will be allowed
History or presence of an abnormal ECG
History of alcoholism or drug addiction prior to period 1 check-in

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GDC-0973 IV InfusionAlso: XL518IV infusion.	Drug	Part 1: GDC-0973 IV Infusion First, Then GDC-0973 Capsules, Part 2: GDC-0973 Capsules First, Then GDC-0973 IV Infusion, Part 2: GDC-0973 IV Infusion First, Then GDC-0973 Capsules
GDC-0973 Oral CapsulesAlso: XL518Oral dose.	Drug	Part 1: GDC-0973 IV Infusion First, Then GDC-0973 Capsules, Part 2: GDC-0973 Capsules First, Then GDC-0973 IV Infusion, Part 2: GDC-0973 IV Infusion First, Then GDC-0973 Capsules

Primary outcome

Maximum Observed Plasma Concentration (Cmax) of IV and Oral GDC-0973
Time frame: Part 2: 0 hours (Hrs) (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Dose Normalized Cmax [Cmax(dn)] of IV and Oral GDC-0973
Time frame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Cmax(dn) is Cmax divided by dose.
Minimum Observed Plasma Trough Concentration (Cmin) of IV and Oral GDC-0973
Time frame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Time to Reach Maximum Observed Plasma Concentration (Tmax) of IV and Oral GDC-0973
Time frame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of IV and Oral GDC-0973
Time frame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t).
Dose Normalized AUC (0-t) [AUC (0-t)dn] of IV and Oral GDC-0973
Time frame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t). AUC (0-t)dn is AUC (0-t) divided by dose.
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of IV and Oral GDC-0973
Time frame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
AUC (0 - ∞)= Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Dose Normalized AUC (0 - ∞) [AUC (0 - ∞)dn] of IV and Oral GDC-0973
Time frame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). AUC (0 - ∞)dn is AUC(0 - ∞) divided by dose.
Plasma Decay Half-Life (t1/2) of IV and Oral GDC-0973
Time frame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
t1/2 is the time measured for the plasma concentration of GDC-0973 to decrease by one half.
Systemic Clearance (CL) of IV GDC-0973
Time frame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Apparent Oral Clearance (CL/F) of Oral GDC-0973
Time frame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modelling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Volume of Distribution at Steady State (Vss) of IV GDC-0973
Time frame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose of Day 1
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the apparent volume of distribution at steady-state.
Apparent Volume of Distribution (Vz/F) of Oral GDC-0973
Time frame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F is influenced by the fraction absorbed.
Absolute Oral Bioavailability (F) of GDC-0973
Time frame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
Absolute oral bioavailability is the amount of drug from a formulation that reaches the systemic circulation relative to an IV dose. F = [AUC (0-∞), oral multiplied by Dose IV] divided by [AUC (0-∞), IV multiplied by Dose oral]. Absolute oral bioavailability is determined for drugs which are administered orally. IV dose is 100% in systemic circulation (dosed directly) and hence no estimation is required.
Mean Absorption Time (MAT)
Time frame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1
MAT is mean time required for the drug to reach the central compartment. MAT was estimated from the mean resident time (MRT) from oral and IV administration. MAT was calculated as MRT last of oral dose minus MRT last of IV dose. MAT is analyzed when drug is administered orally (only for non-IV routes of administration).
Amount of Drug Excreted in the Urine (Aeu) of IV and Oral GDC-0973
Time frame: Part 2: 0 to 12, 12 to 24, 24 to 48, 48 to 72, and 72 to 96 Hrs post-dose on Day 1
The cumulative amount of drug excreted in urine over the entire collection interval of 96 hrs was calculated by adding the Aeu of the intervals 0 to 12, 12 to 24, 24 to 48, 48 to 72, and 72 to 96 hrs where Aeu was calculated by multiplying the urine volume within the collection interval by the associated drug concentration.
Renal Clearance (CLR) of IV and Oral GDC-0973
Time frame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1 for plasma; 0 to 12, 12 to 24, 24 to 48, 48 to 72, and 72 to 96 Hrs post-dose for urine
CLR was calculated as Aeu divided by AUC (0 - ∞), where Aeu was amount of drug excreted in urine from time 0 to 96 hrs post-dose and AUC(0 - ∞) was area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity hrs post-dose.
Percent of GDC-0973 Excreted in the Urine (% Excreted) for IV and Oral GDC-0973
Time frame: Part 2: 0 to 12, 12 to 24, 24 to 48, 48 to 72, and 72 to 96 Hrs post-dose
% Excreted is the mean percentage of dose recovery in urine and calculated as: (Aeu divided by dose) multiplied by 100, where Aeu was amount of drug excreted in urine from time 0 to 96 hrs post-dose.

Results and safety

Results posted to the registry on 6 Feb 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1: GDC-0973 IV Infusion First, Then GDC-0973 Capsules	2	2
Part 2: GDC-0973 IV Infusion First, Then GDC-0973 Capsules	6	6
Part 2: GDC-0973 Capsules First, Then GDC-0973 IV Infusion	5	5

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of IV and Oral GDC-0973

Time frame: Part 2: 0 hours (Hrs) (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1. Geometric mean (Geometric Coefficient of Variation). Unit: nanograms per milliliter (ng/mL)

Measure	GDC-0973 2 mg IV n = 11	GDC-0973 20 mg Oral n = 10
Value	20.5 (35.6)	15.2 (26.4)

Population analysed: Full analysis population included participants who were randomized, received study drug, and had at least 1 valid PK parameter.

Primary outcome: Dose Normalized Cmax [Cmax(dn)] of IV and Oral GDC-0973

Time frame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL/mg

Measure	GDC-0973 2 mg IV n = 11	GDC-0973 20 mg Oral n = 10
Value	10.2 (35.6)	0.844 (26.4)

GDC-0973 2 mg IV vs GDC-0973 20 mg Oral: Ratio of LS Means: 8.45 (90% CI 7.08 to 10.08)

Population analysed: Full analysis population.

Primary outcome: Minimum Observed Plasma Trough Concentration (Cmin) of IV and Oral GDC-0973

Time frame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	GDC-0973 2 mg IV n = 11	GDC-0973 20 mg Oral n = 10
Value	0.261 (37.1)	0.546 (70.0)

Population analysed: Full analysis population.

Primary outcome: Time to Reach Maximum Observed Plasma Concentration (Tmax) of IV and Oral GDC-0973

Time frame: Part 2: 0 Hrs (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1. Median (Full Range). Unit: hr

Measure	GDC-0973 2 mg IV n = 11	GDC-0973 20 mg Oral n = 10
Value	0.500 (0.500 to 0.567)	4.00 (2.00 to 8.00)

Population analysed: Full analysis population.

Adverse events

Time frame: Adverse events were recorded from start of study treatment in first period to end of second period (up to 30 days). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
GDC-0973 2 mg IV	0 of 13 (0%)	2 of 13 (15.4%)	Not reported
GDC-0973 20 mg Oral	0 of 12 (0%)	3 of 12 (25%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Isabelle Rooney, M.D., PhD study director

Genentech, Inc.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GDC-0973 IV Infusion and GDC-0973 Oral Capsules in people with Healthy Volunteers, run by Genentech, Inc..

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 May 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Observed Plasma Concentration (Cmax) of IV and Oral GDC-0973 (time frame: Part 2: 0 hours (Hrs) (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, and 192 Hrs post-dose on Day 1). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01249118.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2017.