A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-946 in Healthy Volunteers and in Subjects With Sickle Cell Disease

Study point of contact

Agios Medical Affairs
833-228-8474
[email protected]

Locations

1 United States site

Age

18 to 70 Years

Phase

Phase 1

Study type

Interventional

Gender

All

Interventions

Drug

Compensation

Unknown

About the study

The purpose of the study is to assess the safety and tolerability of AG-946 in healthy
volunteers after oral administration of single ascending doses (SAD) and multiple ascending
doses (MAD) of AG-946 over 14 days of dosing, and to identify a range of doses that are safe
and pharmacologically active in participants with sickle cell disease. The SAD and MAD parts
of the study will be randomized and double-blinded, and will assess the safety,
pharmacokinetics (PK), and pharmacodynamics (PD) of AG-946 as well as the effect of food (SAD
only) on the pharmacokinetics (PK) of AG-946. The sickle cell disease (SCD) part of the study
will be non-randomized and open-label, and is designed to identify 1 or more safe and
tolerable dose(s) of AG-946 with potential activity in the treatment of participants with
sickle cell disease (SCD).

participation requirements

SAD and MAD

– Participant is a healthy male or a female of nonchildbearing potential aged 18 to 55
years inclusive at the time of consent;

– Participant is able to understand and provide informed consent before the conduct of
any protocol-specific screening procedures;

– Participant is willing and able to complete all study assessments and procedures;

– Participant has a bodyweight ≥50 kilograms (kg) and body mass index ≥18.5 and ≤32
kilograms per square meter (kg/m^2) at screening ;

– Participant is in good general health with no clinically significant deviations from
normal in screening medical history, physical examination, vital signs, or
electrocardiogram (ECGs);

– Male participants must agree to be abstinent as part of their usual lifestyle or use
contraception up to 90 days after last dose of study treatment;

– Participant is a non-smoker and has not used nicotine-containing products for at least
3 months prior to screening;

– Participant is willing to refrain from caffeine- or xanthene-containing products (eg,
coffee, tea, cola, chocolate) for 48 hours before the first dose of study treatment
through 7 days after the last dose of study treatment;

– Participant is willing to refrain from marijuana- or cannabinol-containing products
for 7 days before admission through the final visit;

– Participant is willing to refrain from strenuous exercise starting 72 hours before
admission through the final visit;

– Participant is willing to refrain from use of alcohol starting 7 days prior to
admission through final visit;

– Participant agrees not to donate blood products for duration of study participation;

– Male participants must agree not to donate sperm for duration of study and for 90 days
after the last dose.

participation restrictions

SAD and MAD

– Participant has previously enrolled in this study or has received an investigational
drug with 3 months or 5 half-lives of the drug, whichever is longer, before the first
dose of study treatment;

– Participant has previously received AG-946;

– Participant has a heart rate-corrected QT interval (QTc) interval using Fridericia
correction method (QTcF) >450 milliseconds (ms) at screening;

– Participant has used over-the-counter medication (excluding routine vitamins) within 7
days of the first dose of study treatment, unless agreed as not clinically relevant;

– Participant has used acetaminophen greater than 2 grams (g) in any 24-hour period up
to 48 hours before the first dose of study treatment;

– Participants has clinically relevant screening laboratory tests results outside the
normal range;

– Participant has a history of any relevant cardiovascular, renal, hepatic, chronic
respiratory, or gastrointestinal disease; or hematologic, lymphatic, neurologic,
endocrine, psychiatric, musculoskeletal, genitourinary, immunologic, dermatologic, or
connective tissue disease or disorders;

– Participant has a history of serious mental illness, that includes, but is not limited
to schizophrenia, bipolar disorder, or major depression;

– Participant has a history of any primary malignancy, except for basal cell or squamous
cell carcinomas of the skin or cervical carcinoma in situ or other malignancies that
have been curatively treated and with no evidence of disease for at least 5 years
before screening;

– Participant had surgery within 6 months before the first dose of study treatment;

– Participant has a preexisting condition that interferes with normal gastrointestinal
anatomy or motility, and/or hepatic and/or renal function that could interfere with
the absorption, metabolism, and/or excretion of the study treatment or has previously
undergone cholecystectomy;

– Participant has systolic blood pressure (BP) ≥140 mm Hg or a diastolic BP of ≥90 mm Hg
after 10 minutes rest at screening or before the first dosing of study treatment;

– Participant has had surgery within 6 months before the first dose of study treatment;

– Participant has medical or psychological condition deemed by the Investigator to be
likely to interfere with the volunteer’s ability to provide informed consent,
cooperate, and/or participate in the study;

– Participant has a known allergy to any of the excipients or components of the study
treatment;

– Participant tests positive for hepatitis B surface antigen (HBsAg), hepatitis C virus
(HCV) antibody (Ab), or human immunodeficiency virus (HIV) infection -1 or -2 Ab;

– Participant has donated blood, had blood loss of more than 500 milliliters (mL), or
has received transfusion of blood or plasma within 3 months before screening;

– Participant has a history of illicit drug abuse or alcoholism within the last 1 year
before screening;

– Participant has consumed more than 21 units of alcohol a week within the last 1 year
before screening;

– Participant has used prescription drugs within 2 weeks or 5 half-lives (whichever is
longer) before the first dose of study treatment;

– Participant has a positive screen for drugs of abuse or urinary cotinine >200
nanograms per milliliter (ng/mL) at screening or admission; or a positive screen for
alcohol (via urine analysis) at admission;

– Participant has used St. John’s wort within 28 days before the first dose of study
treatment;

– Participant is unwilling to forgo consumption of Seville oranges, grapefruit or
grapefruit juice, grapefruit hybrids, pumeloes, or exotic citrus fruits from 1 day
before the first dose of study treatment through the final visit;

– Participant cannot communicate reliably with the Investigator;

– Participant cannot or is unlikely to cooperate with the requirements of the study;

– Participant has any conditions that, in the judgment of the Investigator, would make
the volunteer unsuitable for enrollment or could interfere with the volunteer’s
participation in, or completion of, the study.

Locations

  • Austin, Texas, United States, PPD Development, LP, 78744 [Recruiting]
Last updated 2021-07-15 Enroll Now