A Single and Multiple Dose Study to Determine the Safety and Tolerability of GBT021601 in Healthy Adult Volunteers - Part A

Exclusion Criteria57

• Positive pregnancy test or currently breastfeeding.
• History or presence of clinically significant allergic diseases (except for untreated,
• asymptomatic, seasonal allergies) at time of dosing, in the opinion of the investigator.
• History or presence of conditions which, in the opinion of the investigator, are known to
• interfere with the absorption, distribution, metabolism, or excretion 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 had an appendectomy are
• eligible for enrollment.
• History or presence of conditions that may place the participant at increased safety risk as determined by the investigator.
• History of surgery or major trauma within 12 weeks of screening, or surgery planned during the study.
• Any signs and/or symptoms of acute illness, including COVID-19, at screening, Day -1, or Day 1.
• Abnormal ECGs collected at screening or Day -1, including QT interval corrected for
• heart rate (HR) using Fridericia’s formula (QTcF) >450 msec for males and >470 msec
• for females, or any cardiac rhythm other than sinus rhythm that is interpreted by the
• investigator to be clinically significant. An additional triplicate ECG may be performed
• to confirm ECG abnormalities (ie, to confirm that a participant is eligible).
• Known personal or family history of congenital long QT syndrome or known family
• history of sudden death.
• Resting bradycardia (HR <45 beats per minute [bpm]) or resting tachycardia
• (HR >100 bpm) at screening or Day -1 based on vital signs measurements. A single
• repeat measurement may be performed to confirm vital sign abnormalities (ie, to confirm
• that a participant is eligible). Each of the readings must be not clinically significant to
• qualify for enrollment into the study.
• Hypertension, defined as resting systolic blood pressure (BP) >140 mmHg or resting
• diastolic BP >90 mmHg at screening or Day -1. A single repeat measurement may be
• performed to confirm vital sign abnormalities (ie, to confirm that a participant is eligible).
• Each of the readings must be not clinically significant per the investigator’s discretion to
• qualify for enrollment into the study.
• History of alcohol abuse or use of drugs of abuse in the 12 months prior to the date of
• consent. Excess alcohol is defined as more than 14 drinks/week for women and 21 drinks/week for men. A drink is defined as 360 mL of beer 150 mL of wine, or 45 mL of spirits.
• Use of prescription medications within 14 days or 5 half-lives, whichever is longer, or
• any over-the-counter (OTC) drugs, including herbal preparations or dietary supplements
• within 7 days or 5 half-lives, whichever is longer, prior to Day -1 or requiring continued use during study participation. Occasional use of acetaminophen/paracetamol (e.g. up to 2g/day) is permitted up to 24 hours before the first dose.
• Consumption of more than 400 mg of caffeine (approximately 4 cups of coffee) per day
• within 30 days of screening or unwillingness to abstain from consumption of caffeine- or
• xanthine-containing products (eg, tea, coffee, chocolate, cola, etc.) from 48 hours prior to
• dosing (Day 1) through Day 7 (Part A) and from 48 hours prior to dosing and through
• Day 21 (Part B).
• Unwillingness to abstain from alcohol from 48 hours prior to dosing (Day 1) through
• Day 29.
• Consumption of grapefruit and/or grapefruit juice within 14 days prior to Day -1 and
• unwillingness to abstain from consumption of grapefruit, grapefruit juice, or Seville
• oranges through the end of the study (follow-up visit).
• Unwillingness to abstain from any strenuous physical exercise (such as weight training or aerobics) from 72 hours prior to dosing (Day 1) through Day 7 for Part A and 72 hours prior to dosing (Day 1) through Day 21 (Part B). Participants are permitted to exercise following the screening visit.
• Has received another investigational drug within 30 days or 5 half-lives, whichever is
• longer, prior to screening, or is currently participating in another trial of an investigational drug (or medical device).
• Prior exposure to GBT021601.
• Donation or loss of more than 470 mL of blood within 90 days, or plasma/platelets within 2 weeks prior to Day -1.
• Positive result for drugs of abuse, alcohol, or cotinine screen at screening or Day -1.
• Positive screen for human immunodeficiency virus (HIV)-1 and HIV-2 antibodies,
• hepatitis A virus immunoglobulin M (IgM) antibody, hepatitis B virus surface antigen, or
• hepatitis C virus antibody at screening.
• Poor venous access as determined by the investigator/site staff.
• Unwilling or unable to consume standard meals (eg, high-fat meal for food effect cohort).
• Involved in the planning or conduct of this study.
• Any other condition or prior therapy that, in the investigator’s opinion, would confound
• or interfere with the evaluation of safety, tolerability, or PK of the investigational product, interfere with study compliance, or preclude informed consent.