| Eligibility |
Inclusion Criteria:
Part A/B/C:
- Signed informed consent in a language understandable to the subject prior to any
study-mandated procedure.
- BMI of 18.0 to 29.9 kg/m2 (inclusive) at Screening.
- SBP 100-139 mmHg, DBP 50-89 mmHg, and pulse rate 50-90 bpm (inclusive), measured on
either arm, after 5 min in the supine position at Screening and on Day -1 in the first
period, if applicable.
- Fertile male subjects (defined as physiologically capable of conceiving a child
according to the investigator's judgment) must agree to refrain from fathering a child
and:
1. be sexually abstinent with women of child-bearing potential or use condoms during
sexual intercourse with women of child-bearing potential from (first) study
treatment administration up to at least 90 days after (last) study treatment
administration. Moreover, it is recommended that women of child-bearing potential
partners of male subjects consistently and correctly use for the same period a
highly effective method of contraception with a failure rate of < 1% per year.
2. to not donate sperm from (first) study treatment administration up to at least 90
days after (last) study treatment administration.
- Body temperature in the range of 35.5° to 37.5 °C at Screening and on Day -1 in the
first period, if applicable.
- 12-lead safety ECG: QTcF = 450 ms, QRS = 110 ms, PR = 220 ms, and resting HR 50-90 bpm
(inclusive) with no clinically relevant abnormalities on 12-lead safety ECG after at
least 5 min in the supine position at Screening and on Day -1 in the first period, if
applicable.
- Normal renal function as confirmed by an estimated glomerular filtration rate = 80
mL/min/1.73 m2 determined at Screening using the Chronic Kidney Disease Epidemiology
Collaboration formula.
Part A/B:
- Healthy male subjects aged between 18 and 55 years (inclusive) at Screening.
Parts C1 to C3 (Adult subjects):
- Healthy male and female subjects aged between 18 and 55 years (inclusive) at Screening.
Parts E1 and E2 (Elderly subjects):
- Healthy male and female subjects aged between 65 and 80 years (inclusive) at Screening.
Parts C1 to C3, E1 and E2 (Female subjects):
- Women of child-bearing potential must have a negative serum pregnancy test at
Screening and a negative urine pregnancy test on Day
- 1. They must consistently and correctly use (from Screening, during the entire study,
and for at least 30 days after last study treatment administration) a highly effective
method of contraception with a failure rate of < 1% per year, or be sexually inactive,
or have a vasectomized partner. If a hormonal contraceptive is used, it must have been
initiated at least 1 month before first study treatment administration.
- Women of child-bearing potential (i.e., postmenopausal [defined as 12 consecutive
months with no menses without an alternative medical cause, confirmed by an FSH test >
40 mIU/mL], or with documented previous bilateral salpingectomy, bilateral salpingo
oophorectomy or hysterectomy, or with premature ovarian failure [confirmed by a
specialist], XY genotype, Turner syndrome, uterine agenesis).
Exclusion Criteria:
Part A/B/C
- History of major medical or surgical disorders, which, in the opinion of the
investigator, are likely to interfere with the absorption, distribution, metabolism,
or excretion of the study treatment (appendectomy and herniotomy allowed,
cholecystectomy not allowed).
- Any circumstances or conditions, which, in the opinion of the investigator, may affect
full participation in the study or compliance with the protocol.
- History or presence of cardiac rhythm disorders (e.g., sinoatrial heart block,
sick-sinus syndrome, 2nd or 3rd degree AV block, long QT syndrome, symptomatic
bradycardia, atrial flutter, or atrial fibrillation).
- Any illness with a potential to increase the risk of the subject based on medical
history.
- Clinically relevant findings in clinical laboratory tests (hematology, clinical
chemistry, and urinalysis) at Screening (and on Day -1 in Part A and C) or any of the
following laboratory parameters out of normal range: ALT, AST, total bilirubin,
creatinine, TSH, and/or hemoglobin, at Screening and on Day -1 in the first period, if
applicable.
- Any signs or symptoms of active, ongoing infection judged to be clinically relevant by
the investigator (special attention should be given to clinical signs and symptoms
consistent with COVID-19).
Part A (A3, effect of food)
- Known lactose intolerance.
- Known hereditary problems of galactose intolerance, Lapp lactase deficiency, or
glucose-galactose malabsorption.
- Inability or unwillingness to completely consume the required high-fat meal.
Part C
- Pregnant or lactating women.
- Relevant history of a suicide attempt or suicidal behavior. Any recent suicidal
ideation within the last 6 months (categories 4 or 5), or any suicidal behavior within
the last 2 years, except for "Non-Suicidal Self-Injurious Behavior" (item also
included in the Suicidal Behavior section), as judged by the investigator using the
Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening.
- Result = 27 in the Mini-Mental State Examination (MMSE®2™), assessed at Screening (E1
and E2 only).
|
