| Eligibility |
Inclusion Criteria:
1. In Part 1, men and women of any ethnic origin between 18 and 49 years of age, in Part
2, men and women of any ethnic origin between 50 and 79 years of age, inclusive, at
the time of Screening.
2. Male subjects must be willing to use appropriate contraception, such as a condom, and
to refrain from sperm donation during the study and until 90 days after study drug
administration.
3. Women of child-bearing potential must agree not to attempt to become pregnant and to
use a highly effective form of birth control during the study and for 90 days after
study drug administration when their sexual partner has not been vasectomized. Highly
effective forms of birth control entail the use of combined (estrogen- and
progestogen-containing) or progestogen-only hormonal contraception associated with
inhibition of ovulation, an intrauterine device (IUD), an intrauterine
hormone-releasing system (IUS) or abstinence.
4. Postmenopausal women must have had =12 months of spontaneous amenorrhea (with
documented follicle-stimulating hormone (FSH) >33.4 IU/L).
5. Surgically sterile women are defined as those who have had a surgical bilateral
oophorectomy with or without hysterectomy, total hysterectomy or tubal ligation at
least six weeks before taking study treatment. In case of oophorectomy alone, the
reproductive status of the woman has to be confirmed by follow-up hormone level
assessment. Women who are surgically sterile must provide documentation of the
procedure by an operative report or by ultrasound.
6. Subject must weigh between 60 and 120 kg, inclusive, and must have a BMI between 18.0
and 30.0 kg/m2, inclusive, at Screening and on Day -1.
7. Subject must be in good health, as determined by a medical history, physical
examination, 12-lead ECG, and clinical laboratory evaluations (congenital non
hemolytic hyperbilirubinemia is acceptable).
8. Subject is willing and able to give their written informed consent to participate in
the study and to abide by the study restrictions.
9. Subject has good upper limb venous access.
Exclusion Criteria:
1. The subject has taken tenoxicam in the 35 days prior to the first administration of
study drug or FXa DOAC or has taken piroxicam in the two weeks prior to the first
administration of study drug or FXa DOAC.
2. The subject has taken any non-aspirin, non-piroxicam, non-steroidal anti-inflammatory
drug (NSAID) in the week prior to the first administration of study drug or FXa DOAC.
3. The subject requires or has taken during the month prior to first administration of
study drug or FXa DOAC, vitamin K for therapeutic reasons. Vitamin K not taken for
therapeutic purposes is acceptable, e.g., as part of a multivitamin supplement.
4. The subject is receiving or requires, for any cause, any anticoagulant or antiplatelet
therapy including warfarin, clopidogrel or aspirin or any other anticoagulant or
antiplatelet agent or has used these therapies in the month prior to the first
administration of study drug or FXa DOAC.
5. The subject has received any prescribed oral, systemic or topical medication,
including any vaccinations, within 14 days prior to the first administration of study
drug or FXa DOAC (with the exception of contraceptives), unless in the opinion of the
Principal Investigator and the Medical Monitor the medication will not interfere with
the study procedures or compromise safety.
6. The subject has used any non-prescribed systemic or topical medication (including
herbal remedies) within one week prior to the first administration of study drug or
FXa DOAC (with the exception of oral vitamin/mineral supplements [including those that
contain vitamin K when not taken for therapeutic purposes] and paracetamol), unless in
the opinion of the Principal Investigator and the Medical Monitor the medication will
not interfere with the study procedures or compromise safety.
7. The subject is currently participating in a clinical study, e.g. attending follow-up
visits or has been administered an investigational drug (new chemical or biological
entity) within 1 month (for small molecules) or 3 months (for biologicals) prior to
administration of the study drug.
8. The subject has donated =500 mL blood, plasma, or platelets in the 3 months prior to
Screening or any other blood amount within 30 days prior to Screening.
9. Because of an increased risk of thrombosis subjects with known diabetes mellitus or a
fasted glucose =7.0 mmol/L at Screening.
10. The subject has any bleeding diathesis, any increased risk of bleeding or, in the
opinion of the Principal Investigator, is at increased risk of the consequences of
bleeding including but not limited to the following:
1. gastro-intestinal ulceration within the last 3 months;
2. known or suspected oesophageal varices;
3. vascular aneurysms or known arteriovenous malformations;
4. history of known major intraspinal or intracerebral vascular abnormalities;
5. history of brain, spinal or ophthalmic surgery within the last year;
6. any intracranial hemorrhage;
7. uncontrolled severe hypertension.
11. The subject has, in the opinion of the Principal Investigator, any increased risk of
thrombosis or thromboembolism including any known thrombophilia, such as
antiphospholipid syndrome, or any past history of provoked or unprovoked arterial or
venous thrombosis, including thromboembolism.
12. The subject has a significant history of drug allergy, as determined by the Principal
Investigator.
13. The subject has at Screening or on Day -1, a supine blood pressure or supine pulse
rate = 150/95 mmHg and >100 beats per minute (bpm), respectively, or < 90/40 mmHg and
40 bpm, respectively, confirmed by a repeat assessment.
14. For Part 1, the subject consumes >21 alcoholic drinks/week for men or >14 alcoholic
drinks/week for women (one unit of alcohol equals ½ pint [285 mL] of beer or lager,
one glass [125 mL] of wine, or 1 measure [25 mL] of spirits) or has a significant
history of alcoholism or drug/chemical abuse, as determined by the Principal
Investigator. For Part 2, the subject consumes >14 alcoholic drinks/week or has a
significant history of alcoholism or drug/chemical abuse, as determined by the
Principal Investigator.
15. The subject has a positive drug screen, alcohol test or cotinine test result at
Screening or on Day -1, confirmed by repeat testing.
16. The female subject has a positive pregnancy test at Screening or on Day -1 or is
lactating.
17. The subject currently smokes or uses nicotine-containing products. Former smokers will
be eligible, provided they have not smoked for at least 1 month prior to
administration of the study drug.
18. The subject has, or has a history of, any clinically significant neurological,
gastrointestinal, renal, hepatic, cardiovascular, psychiatric, respiratory, metabolic,
endocrine, hematological, or other major disorders, as determined by the Principal
Investigator.
19. The subject has a positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody,
or human immunodeficiency virus (HIV) antibody test result at Screening.
20. The subject has an abnormality in the 12-lead ECG at Screening or on Day -1 that, in
the judgement of the Principal Investigator may, during the study, interfere with the
interpretation of 12-lead ECG results, including average QTcF interval >450 msec for
men or >470 msec for women, 2nd or 3rd degree atrioventricular block, complete left
bundle branch block, complete right bundle branch block or Wolff-Parkinson-White
Syndrome, defined as average PR<110 msec, confirmed by a triplicate repeat ECG.
21. The subject has any other condition that, in the opinion of the Principal
Investigator, would compromise the safety of the subject or the subject's ability to
comply with the protocol and complete the study.
22. The subject has renal insufficiency (serum creatinine level > 1.25 times upper limit
of normal (ULN) or estimated glomerular filtration rate (eGFR) of <60 mL/min*1.73m2).
23. The subject has active liver disease (alanine aminotransferase [ALT] or aspartate
aminotransferase [AST] >1.5x ULN, or total bilirubin > 1.5x ULN at Screening or on Day
-1. One re-test is allowed).
24. The subject has previously participated in a clinical study with VMX-C001.
Additional exclusion criteria for Part 2 only:
25. Because of an effect on FXa DOACs, subjects are to be excluded if he/she receives or
has received medication that is an inhibitor of P-glycoprotein or CYP3A4. (e.g.,
clarithromycin, erythromycin and azole-antimycotics such as ketoconazole,
itraconazole, voriconazole and osaconazole or HIV protease inhibitors.) within 30 days
prior to first administration of FXa DOAC.
26. Because of an effect on FXa DOACs, subjects are to be excluded if he/she receives or
has received treatment with CYP3A4 inducers (e.g., St. John's wort, rifampicin,
phenytoin, carbamazepine, phenobarbital) within 30 days prior to first administration
of FXa DOAC.
27. Because of an effect on FXa DOACs, subjects are to be excluded if he/she receives or
has received treatment with selective serotonin reuptake inhibitors (SSRIs) or
selective noradrenaline reuptake inhibitors (SNRIs) within 30 days prior to first
administration of FXa DOAC.
28. The subject has any contra-indication to treatment with FXa DOACs.
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