An Absolute Bioavailability Study in Healthy Participants Comparing Oral to Intravenous Administration of GDC-0973 (Cobimetinib)
4. april 2017 oppdatert av: Genentech, Inc.
A Phase 1, Single Dose, Randomized, Cross-over Absolute Bioavailability Study in Healthy Subjects Comparing Oral to Intravenous Administration of GDC-0973
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 administration.
The secondary objective of Part 2 of this study is to evaluate the safety of GDC-0973 administered orally and intravenously.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
13
Fase
- Fase 1
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år til 55 år (Voksen)
Tar imot friske frivillige
Ja
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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 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
Exclusion Criteria
- 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
- 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)
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Grunnvitenskap
- Tildeling: Randomisert
- Intervensjonsmodell: Crossover-oppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: Part 1: GDC-0973 IV Infusion First, Then GDC-0973 Capsules
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.
|
IV infusion.
Andre navn:
Oral dose.
Andre navn:
|
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Eksperimentell: Part 2: GDC-0973 IV Infusion First, Then GDC-0973 Capsules
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.
|
IV infusion.
Andre navn:
Oral dose.
Andre navn:
|
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Eksperimentell: Part 2: GDC-0973 Capsules First, Then GDC-0973 IV Infusion
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.
|
IV infusion.
Andre navn:
Oral dose.
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of IV and Oral GDC-0973
Tidsramme: 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
|
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
Tidsramme: 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.
|
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
|
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Minimum Observed Plasma Trough Concentration (Cmin) of IV and Oral GDC-0973
Tidsramme: 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
|
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
|
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Time to Reach Maximum Observed Plasma Concentration (Tmax) of IV and Oral GDC-0973
Tidsramme: 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
|
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
|
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Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of IV and Oral GDC-0973
Tidsramme: 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).
|
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
Tidsramme: 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.
|
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
Tidsramme: 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 - ∞).
|
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
Tidsramme: 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.
|
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
Tidsramme: 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.
|
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
Tidsramme: 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.
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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
|
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Apparent Oral Clearance (CL/F) of Oral GDC-0973
Tidsramme: 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.
|
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
|
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Volume of Distribution at Steady State (Vss) of IV GDC-0973
Tidsramme: 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.
|
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
Tidsramme: 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.
|
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
Tidsramme: 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.
|
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
|
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Mean Absorption Time (MAT)
Tidsramme: 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).
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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
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Amount of Drug Excreted in the Urine (Aeu) of IV and Oral GDC-0973
Tidsramme: 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.
|
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
Tidsramme: 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.
|
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
|
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Percent of GDC-0973 Excreted in the Urine (% Excreted) for IV and Oral GDC-0973
Tidsramme: 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.
|
Part 2: 0 to 12, 12 to 24, 24 to 48, 48 to 72, and 72 to 96 Hrs post-dose
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Etterforskere
- Studieleder: Isabelle Rooney, M.D., PhD, Genentech, Inc.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. november 2010
Primær fullføring (Faktiske)
1. januar 2011
Studiet fullført (Faktiske)
1. januar 2011
Datoer for studieregistrering
Først innsendt
24. november 2010
Først innsendt som oppfylte QC-kriteriene
24. november 2010
Først lagt ut (Anslag)
29. november 2010
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
10. mai 2017
Siste oppdatering sendt inn som oppfylte QC-kriteriene
4. april 2017
Sist bekreftet
1. april 2017
Mer informasjon
Begreper knyttet til denne studien
Andre studie-ID-numre
- MEK4952g
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