| Eligibility |
Inclusion Criteria:
Subjects who meet all the following criteria will be considered for inclusion in the study:
1. Healthy adult males and/or females of 18 to 65 years of age (inclusive) at the time of
Screening.
2. Willing and able to provide written informed consent.
3. Body mass index (BMI) = 18.0 and = 30.0 kg/m2 and weight between 40.0 kg and 100.0 kg
(inclusive) at Screening.
4. Medically healthy without CS abnormalities at the Screening Visit or Day -1,
including:
1. Physical examination, vital signs including temperature, HR, respiratory rate,
and blood pressure
2. Triplicate ECGs taken at least 1 minute apart with QTcF interval duration = 450
msec obtained as an average from the triplicate Screening and pre-dose Day 1 ECGs
after at least 5 minutes in a semi-supine, quiet rest position
3. Hematological parameters (including hemoglobin, hematocrit, red blood cells
[RBC], packed cell volume [PCV], mean corpuscular volume [MCV], mean corpuscular
hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC], red cell
distribution width [RDW], platelet count, white blood cell [WBC] and
differential, and reticulocytes) are equal to or greater than the lower limit of
normal (LLN) of the normal range of the reference laboratory
4. Estimated creatinine clearance (CrCl) or glomerular filtration rate (GFR) < 80
mL/min using Cockcroft-Gault formula (calculated creatinine clearance or GFR =
[{140-Age} × Weight {in kg}] \ [72 × Serum creatinine {in mg/dL}] × 0.85 [if
female]); ALT and AST equal to or = 1.5 times the ULN; results of all other
clinical chemistry and urine analytes without any CS abnormality Note: Discussion
between the PI and the Sponsor Medical Monitor (MM) is required regarding any
potentially CS abnormal laboratory value during the pre-dose period.
5. Non-smoker (including tobacco, e-cigarettes, nicotine patches or marijuana) for at
least 1 month prior to randomization, which will be confirmed by urine cotinine test
at Screening and on Day -1 (admission).
6. Willing and able to comply with all study assessments and adhere to the protocol
schedule, including the entire confinement period and the F/U visits.
7. Have suitable venous access for blood sampling.
8. Women of childbearing potential (WOCBP) must have a negative pregnancy test at
Screening and on Day -1 (admission) and be willing to have additional pregnancy tests,
as required, throughout the study.
WOCBP must agree to and comply with using 1 barrier method (e.g., female condom or
male partner using a condom) plus 1 other highly effective method of birth control
(e.g., oral contraceptive pills [OCPs], long-acting implantable hormones, injectable
hormones, intrauterine device [IUD], vasectomized partner), or sexual abstinence, for
the duration of the study (from signing of consent to final F/U visit) and for 30 days
after last IP administration.
WOCBP must also agree not to donate ova or oocytes (i.e., human eggs) during the
study, and for one menstrual cycle after completion of the study To be considered of
non-childbearing potential, a female must have either a tubal ligation, hysterectomy,
bilateral salpingo-oophrectomy, or menopause (last menstruation > 12 months and
follicle-stimulating hormone [FSH] levels = 40 IU/mL at Screening); provision of
written documentation is not required for female sterilization and oral confirmation
is adequate.
Female subjects who are in same-sex relationships are not required to use
contraception.
9. Males must be surgically sterile (> 30 days since vasectomy), abstinent, or if engaged
in sexual relations with a WOCBP, the subject and his partner must be surgically
sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral
oophorectomy) or using an acceptable, highly effective contraceptive method from
Screening until study completion, including the F/U period. Acceptable methods of
contraception include the use of condoms and the use of an effective contraceptive for
the female partner that includes: OCPs, long-acting implantable hormones, injectable
hormones, a vaginal ring or an IUD. Subjects with same-sex partners are eligible when
this is their preferred and usual lifestyle.
Males must not donate sperm for the duration of the study (from signing of consent to
final F/U visit) and for 90 days after last IP administration.
10. Subjects must agree to adhere to the current state and national advice regarding
minimizing exposure to coronavirus disease of 2019 (COVID-19) from the first Screening
Visit until the final F/U visit.
Exclusion Criteria:
1. Pregnant or lactating at Screening or planning to become pregnant (self or partner) at
any time during the study, including the F/U period.
2. History or presence of significant cardiovascular, pulmonary, hepatic, renal,
hematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological
disease, including any acute illness or major surgery within the past 3 months
determined by the PI to be CS.
3. Iron, B12 or folate outside of the normal range at Screening and any history of anemia
(e.g. iron deficiency, B12 or folate deficiency, or hemoglobinopathy).
4. Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or
squamous epithelial carcinomas of the skin that have been resected with no evidence of
metastatic disease for 3 years prior to Screening.
5. Current or chronic history of liver disease or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome).
6. Has/had febrile illness or symptomatic viral, bacterial (including upper respiratory
tract infection) or fungal infection within 2 weeks prior to randomization.
7. Unable to swallow solid, oral dosage forms whole with the aid of water.
8. Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen
(HBsAg), and hepatitis C virus (HCV) antibody.
9. Positive urine drug screen or alcohol breath test at Screening or Day -1, or history
of substance abuse or alcohol abuse (defined as greater than 2 standard drinks on
average each and every day, where 1 standard drink is defined as containing 10 g of
alcohol and is equivalent to 1 can or stubby of mid-strength beer, 30 mL nip of
spirits, or 100 mL of wine) within the previous 6 months.
10. Use of any prescription medication or any over the counter (OTC) medication, including
erythropoietin stimulating agents, herbal products and vitamins, within 7 days prior
to randomization.
Note: An exception is made for hormonal contraceptives and intermittent, as-needed
acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of
transient headache or any other minor ache/pain. Discussion between the PI and the
Sponsor MM is encouraged regarding the acceptability of the prior use of any
medications during the pre-dose period.
11. Any vaccinations or planned vaccinations (including COVID-19 and influenza) within 14
days prior to dosing on Day 1 and for the duration of the study (up to the F/U visit).
12. Documented significant hypersensitivity reaction or anaphylaxis to any medication,
which in the opinion of the Investigator could compromise subject safety.
13. Donation of blood or plasma within 30 days prior to randomization, or loss of whole
blood of more than 500 mL within 30 days prior to randomization, or past receipt of a
blood transfusion at any time.
14. Received an investigational intervention (including an investigational vaccine) or
used an invasive investigational medical device within 30 days (or 5 half-lives
whichever is longer) prior to Day 1.
15. Any other condition or prior therapy, which, in the opinion of the PI, would make the
volunteer unsuitable for this study, including unable to cooperate fully with the
requirements of the study protocol or likely to be non-compliant with any study
requirements.
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