Safety, Pharmacokinetic and Pharmacodynamic Study of the CDK 4/6 Inhibitor G1T28-1
Phase 1
Completed
- Conditions
- Healthy Volunteers
- Interventions
- Drug: G1T28-1 (CDK 4/6 Inhibitor)Drug: Placebo
- Registration Number
- NCT02243150
- Lead Sponsor
- G1 Therapeutics, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 53
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cohort 1 G1T28-1 (CDK 4/6 Inhibitor) 6mg/m2 of G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion Cohort 1 Placebo 6mg/m2 of G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion Cohort 2 G1T28-1 (CDK 4/6 Inhibitor) 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. Cohort 3 G1T28-1 (CDK 4/6 Inhibitor) 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. Cohort 2 Placebo 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. Cohort 3 Placebo 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. Cohort 4 G1T28-1 (CDK 4/6 Inhibitor) 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. Cohort 4 Placebo 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. Cohort 5 G1T28-1 (CDK 4/6 Inhibitor) 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. Cohort 5 Placebo 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. Cohort 6 G1T28-1 (CDK 4/6 Inhibitor) 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. Cohort 6 Placebo 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. Cohort 7 - Bone Marrow Cohort G1T28-1 (CDK 4/6 Inhibitor) 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Pharmacokinetics of G1T28-1 in Plasma: Clearance Day 1 Clearance after intravenous administration
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: terminal half life (T1/2) Day 1 Terminal half-life, defined as 0.693 divided by λzλ
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)
Trial Locations
- Locations (1)
PRA Early Development Clinic
🇳🇱Groningen, Netherlands