A Bioequivalence Study of Two Formulations of Sacubitril/Valsartan 97 mg/103 mg Film-coated Tablets in Healthy Thai Subjects under Fasting Conditions

• Register: TCTR
• Last refreshed on: 29 April 2024
• Main ID: TCTR20230207002
• Date of registration: 07/02/2023
• Prospective Registration: Yes
• Primary sponsor: Dr. Reddys Laboratories Limited
• Public title: A Bioequivalence Study of Two Formulations of Sacubitril/Valsartan 97 mg/103 mg Film-coated Tablets in Healthy Thai Subjects under Fasting Conditions
• Scientific title: A Bioequivalence Study of Two Formulations of Sacubitril/Valsartan 97 mg/103 mg Film-coated Tablets in Healthy Thai Subjects under Fasting Conditions
• Date of first enrolment: 22/05/2023
• Target sample size: 48
• Recruitment status: Pending (Not yet recruiting)
• URL: https://www.thaiclinicaltrials.org/show/TCTR20230207002
• Study type: Interventional
• Study design: Randomized
• Phase: Phase 1

Countries of recruitment

Thailand

Contacts

• Name: Somruedee Chatsiricharoenkul
• Affiliation: Faculty of Medicine SirirajHospital, Mahidol University

• Name: Ariya Khunvichai
• Affiliation: Medica Innova Co., Ltd.

Key inclusion & exclusion criteria

Inclusion criteria: 1. Thai Male/Female must be 18-55 years of age, body weight more than 50.0 kg with body mass index (BMI) of 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 electrocardiogram (ECG) without clinically significant abnormalities 4. Screening visit laboratory values of blood test including hematology(complete blood count (CBC) with differential), serum potassium, fasting blood sugar (FBS), blood urea nitrogen (BUN),creatinine (Cr), and liver function test (aspartate aminotransferase(AST), alanine aminotransferase (ALT), total bilirubin and alkaline phosphatase (ALP)) 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 hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV)and human immunodeficiency virus antibody (anti-HIV) negative 7. Female subject must have serum beta-subunit of human chorionic gonadotropin negative 8. Female subject of childbearing potential or male subject agrees to use an acceptable birth control method from visit 1 to the follow-up 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. 9. Female subject of non-childbearing potential (hysterectomy, both ovaries removed, surgically sterilized or postmenopausal (for at least 12 consecutive months of amenorrhea)) 10. 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. 11. Non-smoker (never smoked or no smoking within the previous 1 year) 12. Refrain from using herbal medications, cannabis containing products, dietary supplements (e.g., St. Johns 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. 13. 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. 14. Subject does not receive Coronavirus Disease 2019 (COVID-19) vaccine within 14 days before screening visit and does not plan to receive COVID-19 vaccine until the follow-up period. 15. Subject must refrain from drinking caffeine and alcohol for at least 72 hours prior to Day 1 and agree to continue their refraining throughout the last collection time-point of Period 4.
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 Angiotensin Converting Enzyme (ACE) inhibitor or Angiotensin-Receptor blocker (ARB) therapy 6. Have serum potassium level more than 5.4 mmol/L 7. 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 8. Have positive result of urine drug abuse testing on opioids(morphine (Mor), methadone (MTD)), cannabinoids (tetrahydrocannabinol (THC)), methamphetamine(Meth), cocaine (Coc) or methylenedioxy-methamphetamine (MDMA) at screening visit or before doseadministration at each period 9. 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 10. Have positive result of alcohol breathing test at screening visit or before dose administration at each period 11. Female subject is pregnant or breast feeding. 12. Difficulties fasting or consuming standard meals 13. Difficulties swallowing whole tablets 14. Donation or loss of whole blood: a. More than or equal to 50 mL and less than or equal to 499 mL within 30 days prior to Day 1 b. More than or equal to 500 mL within 56days prior to Day 1 15. Participation in any investigational drug study within 30 days from screening visit (from the last follow-up visit to the screening visit). Subject who participates in COVID-19 vaccine trial that does not have any intervention during the course of this study (from the expected enrollment date to the expected follow-up visit) can be included in this study.

Age minimum: 18 Years
Age maximum: 55 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure with reduced ejection fraction.
Bioequivalence, sacubitril, valsartan, generic sacubitril, generic valsartan, pharmacokinetics

Bioequivalence, sacubitril, valsartan, generic sacubitril, generic valsartan, pharmacokinetics

Intervention(s)

Experimental Drug,Active Comparator Drug

Sacubitril and Valsartan Sodium Tablets 97 mg/103 mg,EntrestoTM 200 mg

A single oral dose of sacubitril and valsartan 97 mg/103 film-coated tablets, EntrestoTM 200 mg (Reference) or Sacubitril and Valsartan Sodium Tablets 97 mg/103 mg (Test), will be administered along with 240 mL drinking water after an overnight fasting of at least 10 hours. All subjects will not be allowed to drink any fluid 1-hour before and after each drug administration except 240 mL of water, taken with drug. No food will be allowed for 4 hours after dose administration. The products will begiven in a crossover fashion as per the randomization schedule with sequence TRTR and RTRT, where T is test product and R is reference product.,A single oral dose of sacubitril and valsartan 97 mg/103 film-coated tablets, EntrestoTM 200 mg (Reference) or Sacubitril and Valsartan Sodium Tablets 97 mg/103 mg (Test), will be administered along with 240 mL drinking water after an overnight fasting of at least 10 hours. All subjects will not be allowed to drink any fluid 1-hour before and after each drug administration except 240 mL of water, taken with drug. No food will be allowed for 4 hours after dose administration. The products will begiven in a crossover fashion as per the randomization schedule with sequence TRTR and RTRT, where T is test product and R is reference product.

Primary Outcome(s)

Cmax, AUC0-t, AUC0-inf Up to 48.00 hours post-dose Pharmacokinetic parameters will be calculated from sacubitril and valsartan plasma concentrations using non compartmental methods

Secondary Outcome(s)

Tmax, Elimination half-life, Elimination rate constant Up to 48.00 hours post-dose Pharmacokinetic parameters will be calculated from sacubitril and valsartan plasma concentrations using non compartmental methods

Secondary ID(s)

Nil Known

Source(s) of Monetary Support

Dr. Reddys Laboratories Limited

Ethics review

Status: Request not yet submitted
Approval date:
Contact:

[e-mail]

Siriraj Institutional Review Board

024192667 Ext.

[e-mail]

Results

• Date Completed: 23/06/2023