First-in-Human Safety, PK, and Food Effect Study of Single Ascending Doses of G1T38 in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
This first-in-human (FIH) study will provide the first safety and pharmacokinetic (PK) data for G1T38 in humans and will allow further development of G1T38 in patients with cancer.

Official Title
-----------------
First-in-Human Phase 1 Safety, Pharmacokinetic, and Food Effect Study of Single Ascending Doses of G1T38 in Healthy Male and Female Subjects

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Drug: G1T38 (CDK 4/6 Inhibitor)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male and female volunteers, 40-65 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) at screening, and weighing at least 50 kg Nonusers of nicotine-containing products for at least the previous 3 months prior to dosing or nonsmokers 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 examinations, medical history review, ECGs (QTcF interval > 450 milliseconds for males and >470 milliseconds for females), vital signs, and laboratory tests (including positive HIV, hepatitis B and C) Participated in in a previous clinical study with an investigational product in the last 60 days History of any serious allergic reaction to any medication 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 Pregnant or lactating women Any other issues which, in the opinion of the PI, will make the subject ineligible for study participation

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>G1T38 or placebo | Drug: G1T38 (CDK 4/6 Inhibitor)<br>* CDK 4/6 Inhibitor<br>* Other names: G1T38;Drug: Placebo<br>* Placebo<br>|
| Experimental: Cohort 2<br>G1T38 or placebo | Drug: G1T38 (CDK 4/6 Inhibitor)<br>* CDK 4/6 Inhibitor<br>* Other names: G1T38;Drug: Placebo<br>* Placebo<br>|
| Experimental: Cohort 3<br>G1T38 or placebo | Drug: G1T38 (CDK 4/6 Inhibitor)<br>* CDK 4/6 Inhibitor<br>* Other names: G1T38;Drug: Placebo<br>* Placebo<br>|
| Experimental: Cohort 4<br>G1T38 or placebo | Drug: G1T38 (CDK 4/6 Inhibitor)<br>* CDK 4/6 Inhibitor<br>* Other names: G1T38;Drug: Placebo<br>* Placebo<br>|
| Experimental: Cohort 5<br>G1T38 or placebo | Drug: G1T38 (CDK 4/6 Inhibitor)<br>* CDK 4/6 Inhibitor<br>* Other names: G1T38;Drug: Placebo<br>* Placebo<br>|
| Experimental: Cohort 6<br>G1T38 or placebo | Drug: G1T38 (CDK 4/6 Inhibitor)<br>* CDK 4/6 Inhibitor<br>* Other names: G1T38;Drug: Placebo<br>* Placebo<br>|
| Experimental: Cohort 7<br>G1T38 or placebo | Drug: G1T38 (CDK 4/6 Inhibitor)<br>* CDK 4/6 Inhibitor<br>* Other names: G1T38;Drug: Placebo<br>* Placebo<br>|
| Experimental: Cohort 8<br>G1T38 or placebo | Drug: G1T38 (CDK 4/6 Inhibitor)<br>* CDK 4/6 Inhibitor<br>* Other names: G1T38;Drug: Placebo<br>* Placebo<br>|
| Experimental: Cohort 9 - Food Effect<br>G1T38 | Drug: G1T38 (CDK 4/6 Inhibitor)<br>* CDK 4/6 Inhibitor<br>* Other names: G1T38;|
| Experimental: Cohort 10<br>G1T38 or placebo | Drug: G1T38 (CDK 4/6 Inhibitor)<br>* CDK 4/6 Inhibitor<br>* Other names: G1T38;Drug: Placebo<br>* Placebo<br>|
| Experimental: Cohort 11<br>G1T38 or placebo | Drug: G1T38 (CDK 4/6 Inhibitor)<br>* CDK 4/6 Inhibitor<br>* Other names: G1T38;Drug: Placebo<br>* Placebo<br>|
| Experimental: Cohort 12<br>G1T38 or placebo | Drug: G1T38 (CDK 4/6 Inhibitor)<br>* CDK 4/6 Inhibitor<br>* Other names: G1T38;Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment Related Adverse Event, including Abnormal Laboratory Events | All AEs, including clinical laboratory, vitals signs, physical examinations and ECGs will be analyzed in all subjects receiving study drug through 7 days post dose of study drug. | Up to Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of G1T38: Maximum Plasma Concentration (Cmax) | The observed peak plasma concentration determined from the plasma | Day 1, 2, 3, 4 and 5 | 
| Pharmacokinetics of G1T38: Area under Curve - plasma concentration (AUC) | Area under the plasma concentration-time curve | Day 1, 2, 3, 4 and 5 | 
| Pharmacokinetics of G1T38: Plasma: terminal half life (T1/2) | G1T38: Plasma- terminal half life (T1/2) | Day 1, 2, 3, 4 and 5 | 
| Pharmacokinetics of G1T38: Plasma - Volume of distribution | Volume of distribution in the terminal elimination phase | Day 1, 2, 3, 4 and 5 |