Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as GDC-0973 IV Infusion
GDC-0973 Infusion · 1 trial · 1 indication
Cmax(dn) is Cmax divided by dose.
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)= 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.
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 - ∞).
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.
t1/2 is the time measured for the plasma concentration of GDC-0973 to decrease by one half.
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
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 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.
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 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.
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).
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.
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.
% 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.
| Arm | Type | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| Name | Type | Description |
|---|---|---|
| GDC-0973 IV Infusion | DRUG | IV infusion. |
| GDC-0973 Oral Capsules | DRUG | Oral dose. |
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 ...
GDC-0973 Infusion is an intravenous formulation of GDC-0973, also called GDC-0973 IV Infusion. It is a small molecule developed by Roche Holding AG (ticker RHHBY). The intravenous route was studied to measure how the drug enters the bloodstream compared with oral dosing.
GDC-0973 Infusion is developed by Roche Holding AG, which trades under the ticker RHHBY. Roche sponsored the clinical study of the intravenous formulation of GDC-0973.
GDC-0973 Infusion is in Phase 1 development. It is an investigational formulation and is not approved. One Phase 1 trial has been completed, and no trials are currently active.
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 and used a controlled, randomized design.
Yes. GDC-0973 Infusion and GDC-0973 IV Infusion refer to the same intravenous formulation of GDC-0973. The IV label reflects the intravenous route of administration used in the completed Phase 1 bioavailability study.
GDC-0973 Infusion was studied in healthy volunteers, not in a patient disease population. The completed Phase 1 trial NCT01249118 compared oral and intravenous administration of GDC-0973 to assess absolute bioavailability in 13 healthy participants.