A single ascending dose trial to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, and food effect of orally administered AS-0871 in healthy subjects

1. Must have signed an ICF prior to screening, indicating that he/she
understands the purpose of, and procedures required for, the trial, and
indicating that he/she is willing to participate in the trial.
2. Healthy males or females of non-childbearing potential, between 18 and 64
years of age, inclusive, at screening.
3. Body Mass Index (BMI) between 18.0 and 30.0 kg/m2, inclusive, at screening.
4. Good physical and mental health as established by medical history, physical
examination, ECG, and vital signs (including temporal body temperature)
recording, and results of biochemistry, haematology, and urinalysis tests
during screening as judged by the investigator.
5. Non-smoker/non-user of nicotine-containing products for at least 3 months
prior to screening, to be confirmed by a urine cotinine dipstick test at
screening and on Day -1 of the first treatment period of each cohort.
6. Availability and willingness to complete the trial and follow the
instructions of the investigator or trial-site personnel.
7. Willing and able to adhere to the prohibitions and restrictions specified in
the protocol.
8. Easy venous accessibility.
9. During the trial (from the day of first trial medication onwards) and for a
minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after the
last trial medication intake, a male subject must agree:
to wear a condom when engaging in any activity that allows for passage of
ejaculate to another person (male subject should also be advised of the benefit
for a female partner to use a highly effective method of contraception as
condom may break or leak);
not to donate sperm for the purpose of reproduction.
Contraceptive use should be consistent with local regulations regarding the use
of contraceptive methods for subjects participating in clinical trials.
10. At screening, a female subject must be not of childbearing potential
defined as:
postmenopausal A postmenopausal state is defined as no menses for > 12 months
without an alternative medical explanation. A high follicle stimulating hormone
(FSH) level (> 40 IU/L or mIU/mL) in the postmenopausal range may be used to
confirm a postmenopausal state in women not using hormonal contraception or
hormone replacement therapy. In the absence of > 12 months of amenorrhea, 2 FSH
measurements have to be available, measured at least 3 months apart,
or
permanently sterile Permanent sterilization methods include hysterectomy,
bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and
bilateral oophorectomy.
11. Female subject, except if postmenopausal, must have a negative highly
sensitive serum (*-human chorionic gonadotropin [*-hCG]) pregnancy test at
screening and female subject must have a negative urine pregnancy test on Day
-1 of the first treatment period of each cohort.
12. Female subject must agree not to donate eggs (ova, oocytes) for the
purposes of assisted reproduction during the trial and for at least 90 days
after the last trial medication intake in the last treatment period.
13. Able to communicate well with the investigator, in the local language, and
to understand and comply with the requirements of the trial.

1. History of or current clinically significant medical illness including (but
not limited to) gastrointestinal, cardiovascular, neurologic, psychiatric,
metabolic, endocrinologic, genitourinary, renal, hepatic, respiratory,
inflammatory, neoplastic, haematologic, or infectious disease, or any other
illness that the investigator considers should exclude the subject or that
could interfere with the interpretation of the trial results.
2. Clinically relevant abnormal values for haematology, biochemistry, or
urinalysis at screening or on Day -1 of the first treatment period, as judged
by the investigator.
3. Values of hepatic aminotransferase (ALT and/or AST) > 1.5 × the upper limit
of normal range (ULN) at screening or on Day -1 of the first treatment period.
4. Values of GGT and/or ALP > 1.25 x ULN at screening or on Day -1 of the first
treatment period.
5. Values of total cholesterol > ULN and LDL cholesterol > 1.25 x ULN at
screening or on Day -1 of the first treatment period.
6. Values of total bilirubin > ULN at screening or on Day -1 of the first
treatment period.
7. Values of urea >1.5 × ULN at screening or on Day -1 of the first treatment
period.
8. A QTcF > 450 ms for male subjects and > 470 ms for female subjects.
9. Clinically significant abnormal complete physical examination at screening
or on Day -1 of the first treatment period, or clinically significant abnormal
symptom-driven physical examination at predose on Day 1 of the first treatment
period (if applicable), or clinically significant abnormal values for vital
signs (including temporal body temperature) or 12-lead ECG at screening or at
predose on Day 1 of the first treatment period, as judged by the investigator.
10. Clinically significant presence or history of allergy or intolerance
(including lactose) as judged by the investigator.
11. Previously demonstrated clinically significant allergy or hypersensitivity
to any of the components of the trial medication (see IB8).
12. Positive serology for hepatitis A virus (HAV) immunoglobulin M (IgM),
hepatitis B virus surface antigen (HBsAg), anti-hepatitis C virus antibodies
(anti-HCV-AB), or anti human immunodeficiency virus antibodies 1 + 2
(anti-HIV-AB 1 + 2) at screening.
13. History of alcohol or drug abuse within the last 2 years before screening
or positive test result(s) for alcohol and/or drugs of abuse at screening or on
Day *1 of the first treatment period of each cohort.
Note: A positive alcohol and/or drug test may be repeated once (as soon as
possible and within the screening period) to exclude a technical error.
Subjects with a negative alcohol and/or drug test at retest may be included.
14. Regular alcohol consumption > 14 units per week (1 unit = a 200-mL glass of
average-strength beer, 25 mL of 40% spirit. A 125-mL glass of wine is 1.5 unit).
15. A history of cancer excluding carcinoma in situ or intra-mucosal cancer.
16. Surgery of gastro-intestinal tract that might interfere with absorption
(subjects who have had cholecystectomy may be included). Subject has currently
significant and active diarrhoea, nausea, or constipation that in the
investigator*s opinion could influence drug absorption or bioavailability.
17. Intake of any disallowed therapies (see Section 5.10, Prior and Concomitant
Medication) before the first trial medication intake.
18. Donation of blood or blood products or substantial loss of blood (more than
500 mL) within 3 months before the first trial medication intake or the
intention to donate blood or blood products during the trial.
19. Participation in a clinical trial of an investigational product or an
experimental medical device within 60 days or within a period less than 5 times
the drug*s half-live, whichever is longer, prior to the first trial medication
intake.
20. Major surgery, fracture, or prolonged immobilization (more than 2 weeks)
within 3 months preceding screening, or surgery has been planned during the
time the subject is expected to participate in the trial.
21. Female subject who is breastfeeding at screening.
22. Trial site employee or immediate family members of a trial site or sponsor
employee.
23. Has previously been enrolled in this trial.