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

NCT02243150 | Completed Phase 1

• 1 other identifier: G1T28-1-01
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (11)

• Pharmacokinetics of G1T28-1 in Plasma: Peak Plasma Concentration (Cmax)

  Day 1, Day 2, Day 3 and Day 4

• Pharmacokinetics of G1T28-1 in Plasma: Time to reach the observed peak plasma concentration (tmax)

  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)

  Day 1

• 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

• 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

Study Arms (7)

Cohort 1

EXPERIMENTAL

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

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

Interventions

G1T28-1 (CDK 4/6 Inhibitor) DRUG

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6; Cohort 7 - Bone Marrow Cohort

Placebo DRUG

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• G1 Therapeutics, Inc.: lead

Study Sites (1)

PRA Early Development Clinic

Groningen, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 33595690 DERIVED

Study Officials

• Renger Tiessen, MD

  PRA Clinic Netherlands

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2014
• First Posted: September 17, 2014
• Study Start: September 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: December 18, 2015
• Last Updated: December 17, 2018

Record last verified: 2015-06

Locations

NL (1)