Bioequivalence Study of Two Formulations of Lisinopril Tablet 20 mg in Healthy Volunteers Under Fasting Conditions

NCT05061901 | Completed Phase 1

• 1 other identifier: LZNP-2020-CPI-FRMT
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-labeled (laboratory blinded), randomized, two period, single-center, crossover, comparative study, where each participant will be randomly assigned to the reference (Zestril®, 20 mg) or the test (Lisinopril, 20 mg) formulation in each period of study (sequences Test-Reference (TR) or Reference-Test (RT)), in order to evaluate if both formulations are bioequivalent

Conditions

Bioequivalence

Outcome Measures

Primary Outcomes (2)

• Cmax of lisinopril in plasma after administration of the test and the reference products.

  Maximum observed concentration in plasma.

  Time points 0.00 (prior to each drug administration) and 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 6.50, 7.00, 7.50, 8.00, 9.00, 10.00, 12.00, 16.00, 20.00, 24.00, 36.00, 48.00, 72.00 hours after each drug administration.

• AUC0-t of lisinopril in plasma after administration of the test and the reference.

  Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration (TLQC) using the linear trapezoidal method.

  Time points 0.00 (prior to each drug administration) and 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 6.50, 7.00, 7.50, 8.00, 9.00, 10.00, 12.00, 16.00, 20.00, 24.00, 36.00, 48.00, 72.00 hours after each drug administration.

Secondary Outcomes (8)

• Tmax of lisinopril in plasma after administration of the test and the reference products.

  Time points 0.00 (prior to each drug administration) and 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 6.50, 7.00, 7.50, 8.00, 9.00, 10.00, 12.00, 16.00, 20.00, 24.00, 36.00, 48.00, 72.00 hours after each drug administration.

• TLQC of lisinopril in plasma after administration of the test and the reference products.

  Time points 0.00 (prior to each drug administration) and 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 6.50, 7.00, 7.50, 8.00, 9.00, 10.00, 12.00, 16.00, 20.00, 24.00, 36.00, 48.00, 72.00 hours after each drug administration.

• AUC0-INF of lisinopril in plasma after administration of the test and the reference products.

  Time points 0.00 (prior to each drug administration) and 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 6.50, 7.00, 7.50, 8.00, 9.00, 10.00, 12.00, 16.00, 20.00, 24.00, 36.00, 48.00, 72.00 hours after each drug administration.

• Residual area of lisinopril in plasma after administration of the test and the reference products.

  Time points 0.00 (prior to each drug administration) and 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 6.50, 7.00, 7.50, 8.00, 9.00, 10.00, 12.00, 16.00, 20.00, 24.00, 36.00, 48.00, 72.00 hours after each drug administration.

• Time point where the log-linear elimination phase begins (TLIN) of lisinopril in plasma after administration of the test and the reference products.

  Time points 0.00 (prior to each drug administration) and 1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 6.50, 7.00, 7.50, 8.00, 9.00, 10.00, 12.00, 16.00, 20.00, 24.00, 36.00, 48.00, 72.00 hours after each drug administration.

Study Arms (2)

Sequence TR

OTHER

19 subjects assigned to the sequence TR will receive a single 20 mg dose of the test product Lisinopril (1 x 20 mg tablet), marked as T in the sequence, in Period 1 and a single 20 mg dose of the reference product Zestril® (1 x 20 mg tablet), marked as R in the sequence, in period 2. These treatments will be administered orally with approximately 200 mL of water, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Lisinopril tablet 20 mg

Sequence RT

OTHER

19 subjects assigned to the sequence RT will receive a single 20 mg dose of the reference product Zestril® (1 x 20 mg tablet), marked as R in the sequence, in Period 1 and a single 20 mg dose of the test product Lisinopril (1 x 20 mg tablet), marked as T in the sequence, in period 2. These treatments will be administered orally with approximately 200 mL of water, in the morning, following a 10-hour overnight fast. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Zestril® tablet 20 mg

Interventions

Lisinopril tablet 20 mg DRUG

Lisinopril is manufactured by Pharmtechnology LLC, Belarus. Each tablet contains 20 mg of lisinopril.

Also known as: The test product

Sequence TR

Zestril® tablet 20 mg DRUG

Zestril® is manufactured by Avara Reims Pharmaceutical Services, France. Each tablet contains 20 mg of lisinopril.

Also known as: The reference product

Sequence RT

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy caucasian men and women aged between 18 to 45 years
• Verified diagnosis "healthy" according to the anamnesis data and the results of standard clinical, laboratory and instrumental examination methods, physical examination and anamnestic examination
• The results of an X-ray or fluorographic examination of the chest organs within the normal range (the results of an examination carried out within 12 months before the start of the study may be provided)
• Satisfactory tolerance of the orthostatic test (the range of increase in heart rate when moving from a prone position to a standing position within 12 - 18 beats per minute)
• Body mass index 18.5-30 kg/m² according to Quetelet's weight-height index
• For female subject:
• the results of the examination of the mammary glands (palpation or mammography) within the normal range according to the data obtained within 12 months before the start of the study;
• non-breastfeeding women;
• negative pregnancy test;
• adherence to reliable methods of contraception for female of childbearing potential: sexual continence, or condom + spermicide, or diaphragm + spermicide, started at least 14 days before the first dose of the study drug; intrauterine contraception is also a reliable method of contraception, installed at least 4 weeks before taking the study drugs in the first period;
• сonsent to use these methods of contraception within 30 days after taking the drug in the second period;
• women who do not use acceptable methods of contraception, if they are considered incapable of childbearing, will also be able to participate in the study: women who have undergone a hysterectomy or tubal ligation, women with a clinical diagnosis of infertility, and women who are in menopause (at least a year without menstruation in the absence of alternative pathologies that may cause the cessation of menstruation);
• in case of using contraceptives (injectable and oral hormonal contraceptives, subcutaneous hormonal implants or intrauterine hormonal therapeutic systems), the latter should be canceled at least 60 days before taking the drug in the first period;

You may not qualify if:

• burdened allergic history, hypersensitivity to any ACE inhibitors, including lisinopril or excipients that are part of any of the investigational drugs, or intolerance to these components;
• a history of angioedema, including associated with the use of ACE inhibitors, idiopathic angioedema, hereditary angioedema;
• clinically significant pathologies of the cardiovascular, bronchopulmonary, neuroendocrine systems, as well as diseases of the gastrointestinal tract, liver, kidneys and blood;
• other diseases that, in the opinion of the researcher, may affect the absorption, distribution, metabolism or excretion of both drugs, or increase the risk of negative consequences for the volunteer;
• the presence of mental disorders, including a history;
• surgical interventions on the gastrointestinal tract, with the exception of appendectomy;
• acute infectious diseases that ended less than 4 weeks before taking the drug in the first period;
• dehydration due to diarrhea, vomiting or other reason within the last 24 hours before taking the drug in the first period of the study;
• clinically significant abnormalities on the ECG, the level of systolic blood pressure (SBP) measured in the sitting position at the time of screening ≤ 100 mm Hg or ≥ 130 mm Hg and / or diastolic blood pressure (DBP) ≤ 60 mm Hg or ≥ 85 mm Hg;
• heart rate less than 60 beats/min or more than 90 beats/min at the time of screening, respiratory rate less than 12 or more than 18 per minute at the time of screening, body temperature below 36.0 ° C or above 37.0 °C at the time of screening;
• unsatisfactory tolerance of the orthostatic test (the difference between the heart rate values when moving from a prone position to a standing position is less than 12 or more than 18 beats per minute;
• the use of injectable and oral hormonal contraceptives, subcutaneous hormonal implants or intrauterine hormonal therapeutic systems and other hormonal contraceptives for 60 days before taking the drug in the first period;
• use of any drugs including herbs and food additives, vitamins that can have a significant effect on the PK of lisinopril or data on the effect of which on the pharmacokinetics of lisinopril are unknown, as well as question the characterization of the volunteer as healthy, less than 14 days before taking the drug in the first period;
• donation of plasma or blood (450 ml or more) less than 2 months before taking the drug in the first period;
• consumption of caffeine and xanthine-containing drinks and products (tea, coffee, chocolate, cola, etc.), products containing poppy seeds, less than 48 hours before taking the drug in the first period;

Sponsors & Collaborators

• Pharmtechnology LLC: lead
• ClinPharmInvest, LLC: collaborator

Study Sites (1)

Private healthcare institution "Clinical Hospital "RZD-Medicine" of the city of Yaroslavl"

Yaroslavl, Yaroslavl Oblast, 150047, Russia

Location

MeSH Terms

Interventions

Lisinopril

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Alexander Khokhlov

  ClinPharmInvest, LLC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2021
• First Posted: September 30, 2021
• Study Start: October 6, 2021
• Primary Completion: November 6, 2021
• Study Completion: November 6, 2021
• Last Updated: July 7, 2022

Record last verified: 2022-07

Locations

RU (1)