Clinical trial NCT02243150: Safety, Pharmacokinetic and Pharmacodynamic Study of the CDK 4/6 Inhibitor G1T28-1
Official title: First-In-Human Phase 1 Safety, Pharmacokinetic and Pharmacodynamic Study of G1T28-1 in Healthy Male and Female Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: G1 Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2014-09-17
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


Eligibility 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

Primary outcomes:
measure: Adverse Events
timeFrame: Up to day 14
Secondary outcomes:
measure: Pharmacokinetics of G1T28-1 in Plasma: Peak Plasma Concentration (Cmax)
timeFrame: Day 1, Day 2, Day 3 and Day 4
measure: Pharmacokinetics of G1T28-1 in Plasma: Time to reach the observed peak plasma concentration (tmax)
timeFrame: Day 1, Day 2, Day 3 and Day 4
measure: Pharmacokinetics of G1T28-1 in Plasma: Area under the plasma concentration -time curve from 0-12 hrs (AUC 0-12)
timeFrame: Day 1
measure: Pharmacokinetics of G1T28-1 in Plasma: Area under the plasma concentration- time curve from 0 to last (AUC 0-last)
timeFrame: Day 1, Day 2, Day 3, Day 4
measure: Pharmacokinetics of G1T28-1 in Plasma: Area under the plasma concentration-time curve from time zero to infinity
timeFrame: Day 1, Day 2, Day 3, Day 4
measure: Pharmacokinetics of G1T28-1 in Plasma: terminal half life (T1/2)
timeFrame: Day 1
measure: Pharmacokinetics of G1T28-1 in Plasma: Terminal phase rate constant
timeFrame: Day 1
measure: Pharmacokinetics of G1T28-1 in Plasma: Clearance
timeFrame: Day 1
measure: Pharmacokinetics of G1T28-1 in Plasma: Volume of distribution
timeFrame: Day 1
measure: Pharmacodynamics-Whole Blood Ex Vivo Stimulation
timeFrame: Day 1
measure: Pharmacodynamic - Bone Marrow Analysis
timeFrame: Day 1
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: PRA Early Development Clinic
Study officials:
affiliation: PRA Clinic Netherlands
name: Renger Tiessen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.