Healthy Volunteers
Conditions
Brief summary
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.
Interventions
DRUGG1T28-1 (CDK 4/6 Inhibitor)
DRUGPlacebo
Sponsors
G1 Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of G1T28-1 in Plasma: Peak Plasma Concentration (Cmax) | Day 1, Day 2, Day 3 and Day 4 | The observed peak plasma concentration determined from the plasma concentration vs. time data |
| Pharmacokinetics of G1T28-1 in Plasma: Time to reach the observed peak plasma concentration (tmax) | 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 |
| Pharmacokinetics of G1T28-1 in Plasma: Area under the plasma concentration -time curve from 0-12 hrs (AUC 0-12) | Day 1 | Area under the plasma concentration-time curve from 0 to 12 hours post dosing, calculated by linear/log trapezoidal method |
| Pharmacokinetics of G1T28-1 in Plasma: Area under the plasma concentration- time curve from 0 to last (AUC 0-last) | 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 |
| Pharmacokinetics of G1T28-1 in Plasma: Area under the plasma concentration-time curve from time zero to infinity | Day 1, Day 2, Day 3, Day 4 | Area under the concentration time curve from time zero extrapolated to infinity |
| Pharmacokinetics of G1T28-1 in Plasma: Clearance | Day 1 | Clearance after intravenous administration |
| Pharmacokinetics of G1T28-1 in Plasma: Terminal phase rate constant | Day 1 | Determined by linear regression of at least 3 points on the terminal phase of the log-linear plasma concentration-time curve. |
| Pharmacokinetics of G1T28-1 in Plasma: Volume of distribution | Day 1 | Volume of distribution in the terminal elimination phase |
| Pharmacodynamics-Whole Blood Ex Vivo Stimulation | Day 1 | Analysis of peripheral blood cell proliferation |
| Pharmacodynamic - Bone Marrow Analysis | Day 1 | Analysis of hematopoietic stem and progenitor cell (HSPC) |
| Pharmacokinetics of G1T28-1 in Plasma: terminal half life (T1/2) | Day 1 | Terminal half-life, defined as 0.693 divided by λzλ |
Countries
Netherlands
Outcome results
None listed