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

December 14, 2018 updated by: G1 Therapeutics, Inc.

First-In-Human Phase 1 Safety, Pharmacokinetic and Pharmacodynamic Study of G1T28-1 in Healthy Male and Female Subjects

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
53

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Groningen, Netherlands
        • PRA Early Development Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort 1
6mg/m2 of G1T28-1 or placebo will be administered in 50mL of 5% dextrose by IV infusion
Drug: Placebo
Drug: G1T28-1 (CDK 4/6 Inhibitor)
Experimental: Cohort 2
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: Placebo
Drug: G1T28-1 (CDK 4/6 Inhibitor)
Experimental: Cohort 3
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: Placebo
Drug: G1T28-1 (CDK 4/6 Inhibitor)
Experimental: Cohort 4
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: Placebo
Drug: G1T28-1 (CDK 4/6 Inhibitor)
Experimental: Cohort 5
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: Placebo
Drug: G1T28-1 (CDK 4/6 Inhibitor)
Experimental: Cohort 6
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: Placebo
Drug: G1T28-1 (CDK 4/6 Inhibitor)
Experimental: Cohort 7 - Bone Marrow Cohort
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)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Adverse Events
Time Frame: 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.
Up to day 14

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pharmacokinetics of G1T28-1 in Plasma: Peak Plasma Concentration (Cmax)
Time Frame: Day 1, Day 2, Day 3 and Day 4
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)
Time Frame: 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
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)
Time Frame: Day 1
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)
Time Frame: 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
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
Time Frame: Day 1, Day 2, Day 3, Day 4
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)
Time Frame: Day 1
Terminal half-life, defined as 0.693 divided by λzλ
Day 1
Pharmacokinetics of G1T28-1 in Plasma: Terminal phase rate constant
Time Frame: Day 1
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
Time Frame: Day 1
Clearance after intravenous administration
Day 1
Pharmacokinetics of G1T28-1 in Plasma: Volume of distribution
Time Frame: Day 1
Volume of distribution in the terminal elimination phase
Day 1
Pharmacodynamics-Whole Blood Ex Vivo Stimulation
Time Frame: Day 1
Analysis of peripheral blood cell proliferation
Day 1
Pharmacodynamic - Bone Marrow Analysis
Time Frame: Day 1
Analysis of hematopoietic stem and progenitor cell (HSPC)
Day 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
G1 Therapeutics, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Renger Tiessen, MD, PRA Clinic Netherlands

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 18, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 9, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 16, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 17, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 17, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 14, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2015

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • G1T28-1-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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