A GBT021601 ADME Microtracer Study in Healthy Volunteers

Study Overview
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Brief Summary
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An Open-label Study of GBT021601 in 8 to 10 healthy male or female participants to evaluate the absorption, distribution, metabolism, and excretion (ADME) of GBT021601.

Detailed Description
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This is an open-label Study administering GBT021601 as a single oral dose of 200 mg in healthy participants.

Official Title
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A PHASE 1 STUDY TO ASSESS THE MASS BALANCE, EXCRETION, AND PHARMACOKINETICS OF [14C]-GBT021601, AN ORAL HEMOGLOBIN SPOLYMERIZATION INHIBITOR, IN HEALTHY PARTICIPANTS

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: GBT021601


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI): 18.0 to 27.0 kg/m2, inclusive, at screening. Body weight ≥ 50 kg at screening Females must be nonlactating and nonpregnant (as confirmed by a negative serum pregnancy test at screening and admission for all females), or of nonchildbearing potential (ie, either surgically sterilized or physiologically incapable of becoming pregnant, or at least 1 year postmenopausal [defined as at least 12 months no menses, and confirmed by a follicle-stimulating hormone test, at screening]). Creatinine clearance (glomerular filtration rate) as estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula: ≥90 mL/min, at screening. Exclusion Criteria: History or presence of conditions which, in the opinion of the Investigator, are known to interfere with the ADME of drugs, such as previous surgery on the gastrointestinal tract (including removal of parts of the stomach, bowel, liver, gall bladder, or pancreas). Participants who have a history of appendectomy are eligible for enrollment. History of chronic constipation, or recent complaints of an irregular defecation Significant and/or acute illness at screening or within 5 days prior to study drug administration that may impact safety assessments, in the opinion of the Investigator. Known personal or family history of congenital long QT syndrome or known family history of sudden death. Participation in another ADME study with a radiation burden >0.1 mSv in the period of 1 year prior to screening.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>open-label GBT021601 | Drug: GBT021601<br>* Single oral dose of 200 mg GBT021601, containing  74 kBq ( 2 µCi) of [14C]-GBT021601<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the whole blood and plasma concentrations of 14C-GBT021601 total radioactivity. | Total radioactivity pharmacokinetics concentration over time profiles. | Day 1 to Day 206, maximum | 
| To assess the mass balance by determining 14C-GBT021601 total radioactivity excreted in urine and feces. | Excretion of total radioactivity in urine and feces. | Day 1 to Day 206, maximum | 
| To determine the pharmacokinetics of GBT021601 in whole blood, plasma, and urine. | GBT021601 pharmacokinetics concentration over time profiles in whole blood and plasma. Amount of GBT021601 excreted in urine. | Day 1 to Day 206, maximum | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety and tolerability of GBT021601 administration in healthy participants. | Number of participants with adverse events | Baseline to Day 206, maximum | 
| To characterize and identify metabolites of 14C-GBT021601 in whole blood, plasma, urine, and feces. | Identification of metabolites in whole blood, plasma, urine, and feces. | Day 1 to Day 206, maximum |