Safety, Pharmacokinetic and Pharmacodynamic Study of the CDK 4/6 Inhibitor G1T28-1

G1 Therapeutics

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: Placebo; Drug: G1T28-1 (CDK 4/6 Inhibitor)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02243150

G1T28-1-01

Details and patient eligibility

About

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.

Enrollment: 53 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Double Blind

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53 participants in 7 patient groups

Cohort 1

Experimental group

Description:

6mg/m2 of G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion

Treatment:

Drug: G1T28-1 (CDK 4/6 Inhibitor)

Drug: Placebo

Cohort 2

Experimental group

Description:

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.

Treatment:

Drug: G1T28-1 (CDK 4/6 Inhibitor)

Drug: Placebo

Cohort 3

Experimental group

Description:

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.

Treatment:

Drug: G1T28-1 (CDK 4/6 Inhibitor)

Drug: Placebo

Cohort 4

Experimental group

Description:

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.

Treatment:

Drug: G1T28-1 (CDK 4/6 Inhibitor)

Drug: Placebo

Cohort 5

Experimental group

Description:

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.

Treatment:

Drug: G1T28-1 (CDK 4/6 Inhibitor)

Drug: Placebo

Cohort 6

Experimental group

Description:

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.

Treatment:

Drug: G1T28-1 (CDK 4/6 Inhibitor)

Drug: Placebo

Cohort 7 - Bone Marrow Cohort

Experimental group

Description:

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.

Treatment:

Drug: G1T28-1 (CDK 4/6 Inhibitor)