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GDC-0973 Infusion

Phase 1

Healthy Volunteers | Small molecule | Other |Roche Holding AG|Last Updated: May 10, 2017

Success Probability

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Market & Valuation

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Trial Design

RandomizedCONTROLLED
Total Trials1
Total Enrollment13

FDA Designations

No designations recorded

Clinical trial landscape

GDC-0973 Infusion · 1 trial · 1 indication

Phase 1 1
NCT01249118An Absolute Bioavailability Study in Healthy Participants Comparing Oral to Intravenous Administration of GDC-0973 (Cobimetinib)Healthy Volunteers
COMPLETED13 Analytics
PHASE1COMPLETED
An Absolute Bioavailability Study in Healthy Participants Comparing Oral to Intravenous Administration of GDC-0973 (Cobimetinib)
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Study Endpoints

Primary Endpoints

Maximum Observed Plasma Concentration (Cmax) of IV and Oral GDC-0973
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
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
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
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
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
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
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
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
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
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
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
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
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
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)
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
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
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
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.

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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelCROSSOVER
PurposeBASIC_SCIENCE

Treatment Arms

ArmTypeDescription
Part 1: GDC-0973 IV Infusion First, Then GDC-0973 CapsulesEXPERIMENTALParticipants 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 CapsulesEXPERIMENTALParticipants 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 InfusionEXPERIMENTALParticipants 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.

Interventions

NameTypeDescription
GDC-0973 IV InfusionDRUGIV infusion.
GDC-0973 Oral CapsulesDRUGOral dose.
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Eligibility Criteria

Age Range18 Years to 55 Years
SexALL
Healthy VolunteersYes

Inclusion Criteria * 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 ...

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Frequently asked questions about GDC-0973 Infusion

What is GDC-0973 Infusion used for?

GDC-0973 Infusion is a small molecule being studied in healthy volunteers to assess its absolute bioavailability. It is administered intravenously and compared to oral administration of GDC-0973 (cobimetinib) in a Phase 1 clinical trial. The drug is investigational and not yet approved for any condition.

Who makes GDC-0973 Infusion?

GDC-0973 Infusion is developed by Roche Holding AG, traded on the OTC market under the ticker RHHBY. The company is conducting clinical research on this investigational small molecule drug.

What phase is GDC-0973 Infusion in?

GDC-0973 Infusion is in Phase 1 clinical development. It is an investigational drug, meaning it has not been approved by regulatory authorities. The Phase 1 trial has been completed.

What clinical trials is GDC-0973 Infusion in?

GDC-0973 Infusion was studied in one completed Phase 1 trial, NCT01249118, titled "An Absolute Bioavailability Study in Healthy Participants Comparing Oral to Intravenous Administration of GDC-0973 (Cobimetinib)." The trial enrolled 13 healthy volunteers aged 18 years and older.

Is GDC-0973 Infusion the same as cobimetinib?

GDC-0973 Infusion is the intravenous form of GDC-0973, which is also known as cobimetinib. The clinical trial compares oral administration of GDC-0973 (cobimetinib) to intravenous administration of GDC-0973 Infusion to measure absolute bioavailability.