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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | 6mg/m2 of G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion |
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| Cohort 2 | Experimental | 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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| Cohort 3 | Experimental | 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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| Cohort 4 | Experimental | 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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| Cohort 5 | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| G1T28-1 (CDK 4/6 Inhibitor) | Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics of G1T28-1 in Plasma: Peak Plasma Concentration (Cmax) | 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Renger Tiessen, MD | PRA Clinic Netherlands | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PRA Early Development Clinic | Groningen | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33595690 | Derived | Li C, Hart L, Owonikoko TK, Aljumaily R, Rocha Lima CM, Conkling PR, Webb RT, Jotte RM, Schuster S, Edenfield WJ, Smith DA, Sale M, Roberts PJ, Malik RK, Sorrentino JA. Trilaciclib dose selection: an integrated pharmacokinetic and pharmacodynamic analysis of preclinical data and Phase Ib/IIa studies in patients with extensive-stage small cell lung cancer. Cancer Chemother Pharmacol. 2021 May;87(5):689-700. doi: 10.1007/s00280-021-04239-9. Epub 2021 Feb 17. |
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| Cohort 6 | Experimental | 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 | Experimental | 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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| Placebo | Drug |
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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) | 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) | 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 | 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) | Terminal half-life, defined as 0.693 divided by λzλ | Day 1 |
| Pharmacokinetics of G1T28-1 in Plasma: Terminal phase rate constant | 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 | Clearance after intravenous administration | Day 1 |
| Pharmacokinetics of G1T28-1 in Plasma: Volume of distribution | Volume of distribution in the terminal elimination phase | Day 1 |
| Pharmacodynamics-Whole Blood Ex Vivo Stimulation | Analysis of peripheral blood cell proliferation | Day 1 |
| Pharmacodynamic - Bone Marrow Analysis | Analysis of hematopoietic stem and progenitor cell (HSPC) | Day 1 |