A Study to Evaluate GBT021601 in Single and Multiple Doses in Healthy Participants

Study Overview
=================
Brief Summary
-----------------
This first in human study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and food effect of GBT021601, a hemoglobin S (HbS) polymerization inhibitor, in healthy participants.

Detailed Description
-----------------
This is a randomized, double-blind, placebo controlled, single and multiple ascending dose study in healthy participants.

Official Title
-----------------
A Double-Blind, Randomized, Placebo-Controlled, Single and Multiple Ascending Dose (SAD/MAD) Study to Evaluate the Safety, Tolerability, PK, and Food Effect of GBT021601, a Hemoglobin S Polymerization Inhibitor, in Healthy Participants.

Conditions
-----------------
Sickle Cell Disease

Intervention / Treatment
-----------------
* Drug: GBT021601


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy males and females ≥ 18 to ≤ 55 years of age Body mass index ≥ 18.0 to ≤ 30.0 kg/m2 Body weight ≥ 50 kg at screening and Day -1 Exclusion Criteria: - Positive pregnancy test or currently breastfeeding.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo as a tablet or capsule with dose based off of preceding cohort's data. | Drug: GBT021601<br>* Administered orally with water as a single dose in the morning.<br>* Other names: Placebo;|
| Experimental: GBT021601<br>GBT021601 as a tablet or capsule with dose based off of preceding cohort's data. | Drug: GBT021601<br>* Administered orally with water as a single dose in the morning.<br>* Other names: Placebo;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, as assessed by frequency and severity of adverse events (AEs) | AEs will be coded to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA) and summarized. | 119 days from screening Part A, 134 days from screening Part B | 
| Safety, as assessed by changes in Heart Rate. | Number of participants with changes in heart rate (bpm) as compared to baseline. | 119 days from screening Part A, 134 days from screening Part B | 
| Safety, as assessed by changes in eGFR | Number of participants with changes in eGFR from baseline | 119 days from screening Part A, 134 days from screening Part B | 
| Safety, as assessed by changes in alanine aminotransferase (ALT) | Number of participants with changes in alanine aminotransferase (ALT) | 119 days from screening Part A, 134 days from screening Part B | 
| Safety, as assessed by changes in Blood pressure | Number of participants with changes in systolic (mmHg) and diastolic (mmHg) blood | 119 days from screening Part A, 134 days from screening Part B | 
| Plasma concentration | Time of Cmax | 119 days from screening Part A | 
| Plasma concentration | Cmax on D1-D15 | 134 days from screening Part B | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine whole blood concentration of GBT021601 | Hemoximetry will be used to assess oxygen saturation in whole blood by generating oxygen equilibrium curves (OECs) which relate the extent of Hb-O2 saturation to the partial pressure of O2 (pO2) and measure the binding affinity of O2 to Hb. | 119 days from screening Part A | 
| Determine plasma concentration of GBT021601. | With dosing data from each cohort determine the steady-state maximum plasma/whole blood concentration (Cmax). | 134 days from screening Part B | 
| Safety, as assessed by changes in QTcF | Number of participants with changes in the QTcF interval from baseline | 119 days from screening Part A, 134 days from screening Part B |