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

Phase 1

Completed

• Conditions: Chronic Heart Failure
• Interventions: Drug: Sacubitril and Valsartan-Test product; Drug: Sacubitril and Valsartan-Reference product

• Registration Number: NCT06922253
• Lead Sponsor: Humanis Saglık Anonim Sirketi

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-12-28
• Primary Completion: 2025-01-20
• Study Completion: 2025-03-17
• Status Verified: 2025-04
• Study First Submitted: 2025-04-03
• Study First Submitted QC: 2025-04-03
• Last Update Submitted: 2025-04-03
• Study First Posted: 2025-04-10
• Last Update Posted: 2025-04-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sacubitril and Valsartan Tablets	Sacubitril and Valsartan-Test product	Sacubitril and Valsartan 97 mg / 103 mg Tablets
Entresto® (Sacubitril and Valsartan) Tablets	Sacubitril and Valsartan-Reference product	Entresto® (Sacubitril and Valsartan) 97 mg / 103 mg Tablets

Primary Outcome Measures

Name	Time	Method
Peak Plasma Concentration (Cmax)	48.00 hours	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.
Area Under the Curve from time zero to time of last measurable concentration (AUC0-t)	48.00 hours	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).

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Veeda Clinical Research Ltd.; 🇮🇳 Ahmedabad, Gujarat, India