Bioequivalence Study to Compare Sacubitril and Valsartan Tablets (97mg/103mg) Versus Entresto® (Sacubitril and Valsartan) Tablets (97 mg/103 mg)

An Open Label, Balanced, Randomized, Single Dose, Two Treatment, Two Sequence, Four Period, Full-replicate, Oral Bioequivalence Study of Sacubitril and Valsartan 97 mg/103 mg Tablets of Ç.O.S.B., Karaağaç Mahallesi Fatih, Bulvarı No:32, Kapaklı/TEKİRDAĞ and Entresto® (Sacubitril and Valsartan) 97 mg/103 mg Tablets of Novartis Europharm Limited, Irija in Healthy, Adult, Human Subjects Under Fasting Condition.

An open label, balanced, randomized, single dose, two treatment, two sequence, four period, full-replicate, oral bioequivalence Study of Sacubitril and Valsartan 97 mg/103 mg Tablets of HUMANİS SAĞLIK ANONİM ŞİRKETİ Ç.O.S.B., Karaağaç Mahallesi Fatih, Bulvarı No:32, Kapaklı/TEKİRDAĞ and Entresto® (Sacubitril and Valsartan) 97 mg/103 mg Tablets of Novartis Europharm Limited, Irija in healthy, adult, human subjects under fasting condition.

Study Overview

• Status: Completed
• Conditions: Chronic Heart Failure
• Intervention / Treatment: Drug: Sacubitril and Valsartan-Test product; Drug: Sacubitril and Valsartan-Reference product

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• India
  • Gujarat
    • Ahmedabad, Gujarat, India, 380 051
      • Veeda Clinical Research Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Subjects aged between 18 and 45 years (both inclusive).
• Subjects' weight within normal range according to normal values for Body Mass Index (between 18.50 and 30.00 kg/m2) (both inclusive) with minimum of 45 kg weight.
• Subjects with normal health as determined by personal medical history, clinical examination and laboratory examinations within the clinically acceptable range.
• Subject with Creatinine Clearance ≥80 ml/min.
• Subjects having clinically acceptable 12-lead electrocardiogram (ECG).
• Subjects having clinically acceptable chest X-Ray (PA view), if taken.
• Subjects having negative urine screen for drugs of abuse (including amphetamines, barbiturates, benzodiazepines, marijuana, cocaine, and morphine).
• Subjects having negative urine alcohol test / breath alcohol test.
• Non-smokers.
• Subjects willing to adhere to the protocol requirements and to provide written informed consent.
• For male Subjects:

Subjects willing to follow approved birth control methods (a double barrier method) for the duration of the study as judged by the investigator(s), such as (a double barrier method) condom with spermicide, Condom with diaphragm, or abstinence. Subjects willing to refrain from donating sperm during the study period

- For Female Subjects: Female of child bearing potential practicing an acceptable method of birth control for the duration of the study as judged by the investigator(s), such as intrauterine device (IUD), abstinence, bilateral tubal ligation or double barrier contraception, i.e., condom + diaphragm, condom + spermicidal or foam Postmenopausal for at least 1 year, or if less than 1 year, then following acceptable contraceptive measures as mentioned above

• Subjects having negative urine pregnancy test at screening and negative serum β-hCG pregnancy test on admission day of period 01 (only for female subjects).
• Female Subjects who are non-pregnant and non-lactating.

Exclusion Criteria:

• Subjects having hypersensitivity to Sacubitril and Valsartan or related class of drugs or any of its excipients or heparin.
• Subject with the serum potassium level >5.4 mmol/l during screening.
• History or presence of significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunological, dermatological, neurological, urogenital or psychiatric disease or disorder.
• Subjects who undergone any treatment which could bring about induction or inhibition of hepatic microsomal enzyme system within 30 days prior to admission in period 01.
• History or presence of alcoholism or drug abuse.
• History or presence of asthma, urticaria or other significant allergic reactions.
• History or presence of significant gastric and/or duodenal ulceration.
• History or presence of significant thyroid disease, adrenal dysfunction, organic intracranial lesion such as pituitary tumor.
• History or presence of cancer or basal or squamous cell carcinoma.
• Subject having difficulty with donating blood.
• Subjects having difficulty in swallowing solid dosage form like tablets or capsules.
• Use of any prescribed medication or OTC medication including vaccines, vitamins and herbal remedies during last 30 days prior to admission in period 01.
• Subject having major illness within past 03 months.
• Volunteer who have donated blood (1 unit) or participation in a drug research study within past 90 days prior to the first dose of the study drug.
• Consumption of xanthine-containing products, tobacco containing products or alcohol or any alcohol containing products within 48.00 hours prior to admission in period 01.
• Consumption of grapefruit or grapefruit juice containing products within 72.00 hours prior to admission of period 01.
• Positive screening test for any one or more: HIV, Hepatitis B and Hepatitis C.
• History or presence of significant easy bruising or bleeding.
• History or presence of significant recent trauma.
• Subjects who have been on an abnormal diet (for whatever reason) during the four weeks preceding the study.
• Female subjects who are currently breast feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sacubitril and Valsartan Tablets; Sacubitril and Valsartan 97 mg / 103 mg Tablets	Drug: Sacubitril and Valsartan-Test product; 1 tablet of 97 mg Sacubitril / 103 mg Valsartan
Experimental: Entresto® (Sacubitril and Valsartan) Tablets; Entresto® (Sacubitril and Valsartan) 97 mg / 103 mg Tablets	Drug: Sacubitril and Valsartan-Reference product; 1 tablet of 97 mg Sacubitril / 103 mg Valsartan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (Cmax)	If the intra-subject CV of the reference formulation for Cmax is less than or equal to 30%, the conventional acceptance range of 80.00% - 125.00% for bioequivalence will be applied to Cmax.	48.00 hours
Area Under the Curve from time zero to time of last measurable concentration (AUC0-t)	For, AUC0-t, acceptance range for bioequivalence is 80.00 - 125.00% for 90% confidence intervals of the geometric least square means ratio (T/R).	48.00 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve from time zero to time infinite (AUC0-∞)	descriptive statistics	48.00 hours
Time to reach peak plasma concentration (Tmax)	descriptive statistics	48.00 hours
Plasma Elimination Half-Life (t1/2)	descriptive statistics	48.00 hours
The elimination rate constant (Kel)	descriptive statistics	48.00 hours

Collaborators and Investigators

• Sponsor: Humanis Saglık Anonim Sirketi

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2024
• Primary Completion (Actual): January 20, 2025
• Study Completion (Actual): March 17, 2025

Study Registration Dates

• First Submitted: April 3, 2025
• First Submitted That Met QC Criteria: April 3, 2025
• First Posted (Actual): April 10, 2025

Study Record Updates

• Last Update Posted (Actual): April 10, 2025
• Last Update Submitted That Met QC Criteria: April 3, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: 24-VIN-0563

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No