Safety, Pharmacokinetic and Pharmacodynamic Study of the CDK 4/6 Inhibitor G1T28-1
14. december 2018 opdateret af: G1 Therapeutics, Inc.
First-In-Human Phase 1 Safety, Pharmacokinetic and Pharmacodynamic Study of G1T28-1 in Healthy Male and Female Subjects
This first-in-human (FIH) study will provide the first safety, PK, and PD data of G1T28-1 in humans and will allow further development of G1T28 1 in patients with cancer to reduce chemotherapy-induced myelosuppression.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
53
Fase
- Fase 1
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
-
-
-
Groningen, Holland
- PRA Early Development Clinic
-
-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år til 60 år (Voksen)
Tager imod sunde frivillige
Ja
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inclusion Criteria:
- Healthy male and female volunteers, 18-60 years of age; no clinically significant findings reported following detailed physical examination, medical history, vital signs, clinical laboratory tests, and ECGs as deemed by the PI
- Body mass index (BMI) in the range of 18 to 32 kg/m2 (inclusive) and weighing at least 50 kg
- Non-smokers / non-users of nicotine containing products for at least the previous 3 months
- Agreement to use birth control during the study and 3 months post last visit
- Able to comply with all protocol requirements and procedures
Exclusion Criteria:
- Clinically significant abnormalities found during physical examination, medical history review, ECGs (including QTcf interval > 450 msec), vital signs and laboratory tests (including positive test for HIV, hepatitis B and/or C)
- History of any serious allergic reaction to any medication
- Participated in a previous clinical trial with an investigational product in the last 60 days
- Any blood or plasma donation or other loss of blood at a volume exceeding 500 mL within 3 months before dosing
- History of drug or alcohol abuse in the last 2 years and positive test for drug abuse
- Use of any systemic medication within the past 2 weeks, including use of herbal products
- Pregnant or lactating women
- Any other issue which, in the opinion of the PI, will make the subject ineligible for study participation
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Andet
- Tildeling: Randomiseret
- Interventionel model: Enkelt gruppeopgave
- Maskning: Dobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Cohort 1
6mg/m2 of G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion
|
|
|
Eksperimentel: Cohort 2
Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 1; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion.
|
|
|
Eksperimentel: Cohort 3
Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 2; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion.
|
|
|
Eksperimentel: Cohort 4
Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 3; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion.
|
|
|
Eksperimentel: Cohort 5
Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 4; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion.
Subjects from this cohort may be selected to participate in the Whole Blood Ex-Vivo Stimulation group.
|
|
|
Eksperimentel: Cohort 6
Dose of G1T28-1 or placebo will be determined based on the safety and PK data from Cohort 5; G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion.
Subjects from this cohort may be selected to participate in the Whole Blood Ex-Vivo Stimulation group.
|
|
|
Eksperimentel: Cohort 7 - Bone Marrow Cohort
All subjects in this cohort will receive active drug, G1T28-1.
Dose of G1T28-1 will be determined based on the safety and PK data from previous cohorts.
G1T28-1 will be administered in 50mL of 5% dextrose by IV infusion.
Subjects in this cohort will be selected for the Ex-Vivo Stimulation group and will have a one time bone marrow aspirate at one of the following time points: pre dose, 12 or 24 hours post dose.
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Adverse Events
Tidsramme: Up to day 14
|
All Adverse events, including-clinical laboratory data, vital signs and ECGs will be analyzed in all subjects receiving study drug through 14 days post dose of study drug.
|
Up to day 14
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Pharmacokinetics of G1T28-1 in Plasma: Peak Plasma Concentration (Cmax)
Tidsramme: Day 1, Day 2, Day 3 and Day 4
|
The observed peak plasma concentration determined from the plasma concentration vs. time data
|
Day 1, Day 2, Day 3 and Day 4
|
|
Pharmacokinetics of G1T28-1 in Plasma: Time to reach the observed peak plasma concentration (tmax)
Tidsramme: Day 1, Day 2, Day 3 and Day 4
|
The time to reach the observed peak plasma concentration from the plasma concentration vs. time data
|
Day 1, Day 2, Day 3 and Day 4
|
|
Pharmacokinetics of G1T28-1 in Plasma: Area under the plasma concentration -time curve from 0-12 hrs (AUC 0-12)
Tidsramme: Day 1
|
Area under the plasma concentration-time curve from 0 to 12 hours post dosing, calculated by linear/log trapezoidal method
|
Day 1
|
|
Pharmacokinetics of G1T28-1 in Plasma: Area under the plasma concentration- time curve from 0 to last (AUC 0-last)
Tidsramme: Day 1, Day 2, Day 3, Day 4
|
Area under the plasma concentration-time curve from time 0 to time of last measurable concentration calculated by linear/log trapezoidal method
|
Day 1, Day 2, Day 3, Day 4
|
|
Pharmacokinetics of G1T28-1 in Plasma: Area under the plasma concentration-time curve from time zero to infinity
Tidsramme: Day 1, Day 2, Day 3, Day 4
|
Area under the concentration time curve from time zero extrapolated to infinity
|
Day 1, Day 2, Day 3, Day 4
|
|
Pharmacokinetics of G1T28-1 in Plasma: terminal half life (T1/2)
Tidsramme: Day 1
|
Terminal half-life, defined as 0.693 divided by λzλ
|
Day 1
|
|
Pharmacokinetics of G1T28-1 in Plasma: Terminal phase rate constant
Tidsramme: Day 1
|
Determined by linear regression of at least 3 points on the terminal phase of the log-linear plasma concentration-time curve.
|
Day 1
|
|
Pharmacokinetics of G1T28-1 in Plasma: Clearance
Tidsramme: Day 1
|
Clearance after intravenous administration
|
Day 1
|
|
Pharmacokinetics of G1T28-1 in Plasma: Volume of distribution
Tidsramme: Day 1
|
Volume of distribution in the terminal elimination phase
|
Day 1
|
|
Pharmacodynamics-Whole Blood Ex Vivo Stimulation
Tidsramme: Day 1
|
Analysis of peripheral blood cell proliferation
|
Day 1
|
|
Pharmacodynamic - Bone Marrow Analysis
Tidsramme: Day 1
|
Analysis of hematopoietic stem and progenitor cell (HSPC)
|
Day 1
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Efterforskere
- Ledende efterforsker: Renger Tiessen, MD, PRA Clinic Netherlands
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. september 2014
Primær færdiggørelse (Faktiske)
1. februar 2015
Studieafslutning (Faktiske)
18. december 2015
Datoer for studieregistrering
Først indsendt
9. september 2014
Først indsendt, der opfyldte QC-kriterier
16. september 2014
Først opslået (Skøn)
17. september 2014
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
17. december 2018
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
14. december 2018
Sidst verificeret
1. juni 2015
Mere information
Begreber relateret til denne undersøgelse
Andre undersøgelses-id-numre
- G1T28-1-01
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .