Safety, Pharmacokinetic and Pharmacodynamic Study of the CDK 4/6 Inhibitor G1T28-1
14. desember 2018 oppdatert av: 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.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
53
Fase
- Fase 1
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Groningen, Nederland
- PRA Early Development Clinic
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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 60 år (Voksen)
Tar imot friske frivillige
Ja
Kjønn som er kvalifisert for studier
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
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Annen
- Tildeling: Randomisert
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Dobbelt
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: Cohort 1
6mg/m2 of G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion
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Eksperimentell: 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.
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Eksperimentell: 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.
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Eksperimentell: 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.
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Eksperimentell: 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.
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Eksperimentell: 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.
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Eksperimentell: 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.
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Adverse Events
Tidsramme: Up to day 14
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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.
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Up to day 14
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Pharmacokinetics of G1T28-1 in Plasma: Peak Plasma Concentration (Cmax)
Tidsramme: Day 1, Day 2, Day 3 and Day 4
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The observed peak plasma concentration determined from the plasma concentration vs. time data
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Day 1, Day 2, Day 3 and Day 4
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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
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The time to reach the observed peak plasma concentration from the plasma concentration vs. time data
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Day 1, Day 2, Day 3 and Day 4
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Pharmacokinetics of G1T28-1 in Plasma: Area under the plasma concentration -time curve from 0-12 hrs (AUC 0-12)
Tidsramme: Day 1
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Area under the plasma concentration-time curve from 0 to 12 hours post dosing, calculated by linear/log trapezoidal method
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Day 1
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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
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Area under the plasma concentration-time curve from time 0 to time of last measurable concentration calculated by linear/log trapezoidal method
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Day 1, Day 2, Day 3, Day 4
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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
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Area under the concentration time curve from time zero extrapolated to infinity
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Day 1, Day 2, Day 3, Day 4
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Pharmacokinetics of G1T28-1 in Plasma: terminal half life (T1/2)
Tidsramme: Day 1
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Terminal half-life, defined as 0.693 divided by λzλ
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Day 1
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Pharmacokinetics of G1T28-1 in Plasma: Terminal phase rate constant
Tidsramme: Day 1
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Determined by linear regression of at least 3 points on the terminal phase of the log-linear plasma concentration-time curve.
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Day 1
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Pharmacokinetics of G1T28-1 in Plasma: Clearance
Tidsramme: Day 1
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Clearance after intravenous administration
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Day 1
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Pharmacokinetics of G1T28-1 in Plasma: Volume of distribution
Tidsramme: Day 1
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Volume of distribution in the terminal elimination phase
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Day 1
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Pharmacodynamics-Whole Blood Ex Vivo Stimulation
Tidsramme: Day 1
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Analysis of peripheral blood cell proliferation
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Day 1
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Pharmacodynamic - Bone Marrow Analysis
Tidsramme: Day 1
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Analysis of hematopoietic stem and progenitor cell (HSPC)
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Day 1
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Etterforskere
- Hovedetterforsker: Renger Tiessen, MD, PRA Clinic Netherlands
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
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. september 2014
Primær fullføring (Faktiske)
1. februar 2015
Studiet fullført (Faktiske)
18. desember 2015
Datoer for studieregistrering
Først innsendt
9. september 2014
Først innsendt som oppfylte QC-kriteriene
16. september 2014
Først lagt ut (Anslag)
17. september 2014
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
17. desember 2018
Siste oppdatering sendt inn som oppfylte QC-kriteriene
14. desember 2018
Sist bekreftet
1. juni 2015
Mer informasjon
Begreper knyttet til denne studien
Andre studie-ID-numre
- G1T28-1-01
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