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

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ClinicalTrials.gov Identifier: NCT02243150
Recruitment Status : Completed
First Posted : September 17, 2014
Last Update Posted : December 17, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: G1T28-1 (CDK 4/6 Inhibitor) Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 53 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
Official Title: First-In-Human Phase 1 Safety, Pharmacokinetic and Pharmacodynamic Study of G1T28-1 in Healthy Male and Female Subjects
Study Start Date : September 2014
Actual Primary Completion Date : February 2015
Actual Study Completion Date : December 18, 2015

Arm Intervention/treatment
Experimental: Cohort 1
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
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: G1T28-1 (CDK 4/6 Inhibitor)
Drug: Placebo
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: G1T28-1 (CDK 4/6 Inhibitor)
Drug: Placebo
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: G1T28-1 (CDK 4/6 Inhibitor)
Drug: Placebo
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: G1T28-1 (CDK 4/6 Inhibitor)
Drug: Placebo
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: G1T28-1 (CDK 4/6 Inhibitor)
Drug: Placebo
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)



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. Pharmacokinetics of G1T28-1 in Plasma: Clearance [ Time Frame: Day 1 ]
    Clearance after intravenous administration

  9. Pharmacokinetics of G1T28-1 in Plasma: Volume of distribution [ Time Frame: Day 1 ]
    Volume of distribution in the terminal elimination phase

  10. Pharmacodynamics-Whole Blood Ex Vivo Stimulation [ Time Frame: Day 1 ]
    Analysis of peripheral blood cell proliferation

  11. Pharmacodynamic - Bone Marrow Analysis [ Time Frame: Day 1 ]
    Analysis of hematopoietic stem and progenitor cell (HSPC)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02243150


Locations
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Netherlands
PRA Early Development Clinic
Groningen, Netherlands
Sponsors and Collaborators
G1 Therapeutics, Inc.
Investigators
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Principal Investigator: Renger Tiessen, MD PRA Clinic Netherlands

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Responsible Party: G1 Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02243150     History of Changes
Other Study ID Numbers: G1T28-1-01
First Posted: September 17, 2014    Key Record Dates
Last Update Posted: December 17, 2018
Last Verified: June 2015