| Eligibility |
Inclusion Criteria:
1. Thai Male/Female must be 18-55 years of age, body weight >50.0 kg with body mass index
(BMI) = 18.0-30.0 kg/m2, inclusive.
2. Must be in good health as determined by medical history, vital signs (blood pressure
(systolic blood pressure not lower than 100 or not over 139 mmHg, diastolic blood
pressure not lower than 70 or not over 89 mmHg), body temperature, pulse rate,
respiratory rate) and physical examination or showing no clinically significant
abnormalities in the opinion of Principal/Clinical Investigator or designated
physicians
3. Screening ECG without clinically significant abnormalities
4. Screening visit laboratory values of blood test including hematology (CBC with
differential), FBS (Fasting Blood sugar), BUN (Blood urea Nitrogen), Cr, and liver
function test (AST (Aspartate transaminase), ALT (Alanine transaminase) , total
bilirubin and ALP (Alkaline phosphatase)) must be within the normal range or showing
no clinically significant abnormalities in the opinion of Principal/Clinical
Investigator or designated physicians.
5. Urinalysis results within normal limit or showing no clinically significant
abnormalities in the opinion of Principal/Clinical Investigator or designated
physicians.
6. Must have serum HBsAg, anti-HCV and anti-HIV negative
7. Female subject must have serum ß-hCG negative.
8. Subject willing to avoid or follow precautions while driving, operating machinery and
while working on high elevations.
9. Female subject of childbearing potential or male subject agrees to use an acceptable
birth control method from screening visit to the followup visit. The acceptable birth
control method is defined as a barrier method of contraception (including condoms,
intrauterine device and diaphragm with spermicidal agent) or total abstinence from
sexual intercourse from visit 1 to the follow-up visit. Hormonal contraceptives are
not acceptable.
10. Female subject of non-childbearing potential (hysterectomy, both ovaries removed,
surgically sterilized or postmenopausal (for at least 12 consecutive months of
amenorrhea))
11. Female subject must agree not to become pregnant for the entire participation period
and must have a negative result for a urine pregnancy test performing prior to dosing
at Period 1, Period 2, Period 3 and Period 4.
12. Non-smoker (never smoked or no smoking within the previous 1 year)
13. Subject willing to not participate in blood donations (=500 mL) until 56 days after
completion of the study (last subject visit) and willing to not participate in
clinical research studies until 30 days after completion of the study (last subject
visit).
14. Refrain from using herbal medications, cannabis containing products, dietary
supplements (e.g., St. John's Wort, ginkgo biloba, garlic supplements), vitamins,
grapefruit or grapefruit juice, or pomelo within 14 days before the first
administration of investigational product (Day 1). Subjects must agree to refrain from
these items until the last collection time-point of Period 4.
15. Subject must have ended any systemic medications or any medications that have any
impact on gastrointestinal system at least 30 days prior to Day 1 or at least 5 times
of elimination half-life prior to Day 1 and agree to continue their refraining
throughout the follow-up period.
16. Subject must refrain from drinking caffeine and alcohol for at least 48 hours prior to
Day 1 and agree to continue their refraining throughout the last collection time-point
of Period 4.
17. Have the ability to understand the requirements of the study and must voluntarily sign
and date an informed consent, approved by an Independent Ethics Committee
(IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or
study-specific procedures
Exclusion Criteria:
1. Known hypersensitivity to sacubitril or valsartan or any other similar class of drugs
or its components
2. Past medical history of renal and hepatic insufficiency
3. Subject has a history of any illness that, in the opinion of Principal/Clinical
Investigator or designated physicians, might confound the result of the study or pose
an additional risk in administering investigational product to the subject. This may
include but is not limited to: a history of relevant drug or food allergies; history
of cardiovascular, gastrointestinal, central nervous system disease, renal and hepatic
impairment; history or presence of clinically significant illness; or history of
mental illness that may affect compliance with study requirements.
4. History of hereditary or idiopathic angioedema
5. Have a history of angioedema related to previous ACE inhibitor or ARB therapy
6. Have history of drug abuse (in the opinion of Principal/Clinical Investigator or
designated physicians, as judged by medical history) in the last 12 months
7. Have positive result of urine drug abuse testing on opioids (Mor, MTD), cannabinoids
(THC), Meth, Coc or MDMA at screening visit or before dose administration at each
period
8. Alcohol abuse or excessive use (in the opinion of Principal/Clinical Investigator or
designated physicians, as judged by medical history) in the last 12 months
9. Have positive result of alcohol breathing test at screening visit or before dose
administration at each period
10. Female subject is pregnant or breast feeding.
11. Difficulties fasting or consuming standard meals
12. Difficulties swallowing whole tablets
13. Donation or loss of whole blood:
1. =50 mL and =499 mL within 30 days prior to Day 1
2. =500 mL within 56 days prior to Day 1
14. Participation in any investigational drug study within 30 days from screening visit
(from the last follow-up visit to the screening visit).
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